Sample records for abdominal obesity insulin

  1. Elevated fasting insulin levels increase the risk of abdominal obesity in Korean men.

    PubMed

    Park, Sung Keun; Oh, Chang-Mo; Jung, Taegi; Choi, Young-Jun; Chung, Ju Youn; Ryoo, Jae-Hong

    2017-04-01

    This study was designed to investigate whether an elevated fasting insulin level predicts abdominal obesity. A cohort study was conducted with 13,707 non-obese Korean men. They were categorized into 4 groups according to the quartile of fasting insulin level, and followed up from 2005 to 2010. Incidence rates of obesity were compared among the 4 groups during follow-up, and a Cox proportional hazards model was used to calculate hazard ratios (HRs) for abdominal obesity according to fasting insulin level. The overall incidence rate of obesity was 16.2%, but the rate increased in proportion to the fasting insulin level (quartiles 1-4: 9.8%, 12.4%, 16.9%, 25.5%, P<0.001). When HR of the 1st quartile was regarded as the reference, HRs for abdominal obesity increased proportionally to baseline fasting insulin level in an unadjusted model. However, after adjustment for covariates, including baseline waist circumference (WC), only in the quartile 4 group was the statistical significance of the association maintained [quartile 2-4; abdominal obesity: 0.89 (0.76-1.02), 1.00 (0.86-1.14) and 1.24 (1.08-1.43), P for trend <0.001]. Although the risk of incident abdominal obesity was highest in the group with the highest fasting insulin levels, an overall proportional relationship between fasting insulin level and incident abdominal obesity was not found. Additionally, this association was largely accounted for by baseline WC. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Aldosterone Is Not Associated With Metabolic and Microvascular Insulin Sensitivity in Abdominally Obese Men.

    PubMed

    Schütten, Monica T J; Kusters, Yvo H A M; Houben, Alfons J H M; Scheijen, Jean L J M; van de Waarenburg, Marjo P H; Schalkwijk, Casper G; Joris, Peter J; Plat, Jogchum; Mensink, Ronald P; de Leeuw, Peter W; Stehouwer, Coen D A

    2018-02-01

    Impaired insulin-mediated muscle microvascular recruitment (IMMR) may add to the development of insulin resistance and hypertension. Increased aldosterone levels have been linked to these obesity-related complications in severely to morbidly obese individuals and to impaired microvascular function in experimental studies. To investigate whether aldosterone levels are associated with IMMR, insulin sensitivity, and blood pressure in lean and moderately abdominally obese men, and to study the effect of weight loss. In 25 lean and 53 abdominally obese men, 24-hour blood pressure measurement was performed, and aldosterone levels were measured using ultra-performance liquid chromatography tandem mass spectrometry. Insulin sensitivity was assessed by determining whole-body glucose disposal during a hyperinsulinemic clamp. IMMR in forearm skeletal muscle was measured with contrast-enhanced ultrasonography. These assessments were repeated in the abdominally obese men following an 8-week weight loss or weight stable period. Sodium excretion and aldosterone levels were similar in lean and abdominally obese participants, but sodium excretion was inversely associated with aldosterone concentration only in the lean individuals [lean, β/100 mmol sodium excretion (adjusted for age and urinary potassium excretion) = -0.481 (95% confidence interval, -0.949 to -0.013); abdominally obese, β/100 mmol sodium excretion = -0.081 (95% confidence interval, -0.433 to 0.271); P for interaction = 0.02]. Aldosterone was not associated with IMMR, insulin sensitivity, or blood pressure and was unaffected by weight loss. In moderately abdominally obese men, the inverse relationship between sodium excretion and aldosterone concentration is less than that in lean men but does not translate into higher aldosterone levels. The absolute aldosterone level does not explain differences in microvascular and metabolic insulin sensitivity and blood pressure between lean and moderately abdominally obese men

  3. Abdominal obesity in older women: potential role for disrupted fatty acid reesterification in insulin resistance.

    PubMed

    Yeckel, Catherine W; Dziura, James; DiPietro, Loretta

    2008-04-01

    Excess abdominal adiposity is a primary factor for insulin resistance in older age. Our objectives were to examine the role of abdominal obesity on adipose tissue, hepatic, and peripheral insulin resistance in aging, and to examine impaired free fatty acid metabolism as a mechanism in these relations. This was a cross-sectional study. The study was performed at a General Clinical Research Center. Healthy, inactive older (>60 yr) women (n = 25) who were not on hormone replacement therapy or glucose-lowering medication were included in the study. Women with abdominal circumference values above the median (>97.5 cm) were considered abdominally obese. Whole-body peripheral glucose utilization, adipose tissue lipolysis, and hepatic glucose production were measured using in vivo techniques according to a priori hypotheses. In the simple analysis, glucose utilization at the 40 mU insulin dose (6.3 +/- 2.8 vs. 9.1 +/- 3.4; P < 0.05), the index of the insulin resistance of basal hepatic glucose production (23.6 +/- 13.0 vs. 15.1 +/- 6.0; P < 0.05), and insulin-stimulated suppression of lipolysis (35 vs. 54%; P < 0.05) were significantly different between women with and without abdominal obesity, respectively. Using the glycerol appearance rate to free fatty acid ratio as an index of fatty acid reesterification revealed markedly blunted reesterification in the women with abdominal adiposity under all conditions: basal (0.95 +/- 0.29 vs. 1.35 +/- 0.47; P < 0.02); low- (2.58 +/- 2.76 vs. 6.95 +/- 5.56; P < 0.02); and high-dose (4.46 +/- 3.70 vs. 12.22 +/- 7.13; P < 0.01) hyperinsulinemia. Importantly, fatty acid reesterification was significantly (P < 0.01) associated with abdominal circumference and hepatic and peripheral insulin resistance, regardless of total body fat. These findings support the premise of dysregulated fatty acid reesterification with abdominal obesity as a pathophysiological link to perturbed glucose metabolism across multiple tissues in aging.

  4. Bicycling but not walking is independently associated with fasting insulin in abdominally obese women.

    PubMed

    Hemmingsson, Erik; Ekelund, Ulf; Udden, Joanna

    2011-08-01

    The impact of walking and bicycling on insulin resistance (IR) in women with abdominal obesity is unclear. Pooled analysis of data from a randomized trial on physically active commuting (bicycling + walking vs walking only) in women with abdominal obesity [n = 98; age:47.3 ± 7.6 yrs; waist circumference (WC):103.1 ± 7.8 cm]. Bicycling and walking data were collected during 7 consecutive days by trip meters (Trelock FC-410) and pedometers (Yamax digiwalker SW-200) at baseline, 2, 4, and 6 months. Owing to a skew distribution we analyzed bicycling as a binary dummy variable with a 10 km/week cut-off. Fasting serum insulin and homeostatic model assessment - insulin resistance (HOMA-IR) were assessed at baseline and 6 months, as were body mass index (BMI), WC, and dual x-ray absorptiometry (DXA)-assessed % whole-body fat. Increased bicycling by 10 km/wk was associated with reductions in fasting serum insulin at follow-up independent of age, treatment allocation, baseline phenotype, Δ walking, and Δ % body fat (β = -10.9, P = .042), but not HOMA-IR (β = -2.0, P = .13). Increased walking was not associated with fasting serum insulin (P = .33) or HOMA-IR (P = .44) at follow-up, after adjustment for the same covariates and Δ bicycling. Increased bicycling but not walking was associated with reduced insulin levels at follow-up. Bicycling may be more effective than walking for reducing insulin levels in abdominally obese women.

  5. Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

    PubMed

    Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

    2017-07-01

    Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (P<.05) in AO-HPIR than that in AO-LPIR and controls. Postprandial triglycerides AUC was higher (P<.05), whereas high-density lipoprotein cholesterol AUC was lower (P<.05), in AO-HPIR than those in AO-LPIR and controls. Postprandial AUCs for total cholesterol and apolipoprotein B were similar in abdominally obese subjects with different degrees of postprandial insulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with polycystic ovary syndrome.

    PubMed

    Chen, Li; Xu, Wen Ming; Zhang, Dan

    2014-10-01

    To study the expression of insulin signaling-related genes and oxidative stress markers in the visceral adipose tissue obtained from polycystic ovary syndrome (PCOS) patients and healthy control subjects and to investigate the relationships among abdominal obesity, insulin resistance, and oxidative stress at the tissue level. Case-control study. University teaching hospital. In total, 30 PCOS patients and 30 healthy control subjects, who underwent laparoscopic surgery, were included in the study. Abdominal obesity was defined based on waist circumference (WC). The homeostasis model index was used to assess insulin resistance (HOMA-IR). Gene expression of glucose transporter 4 (GLUT4) and insulin receptor substrate 1 (IRS1) in visceral adipose tissue (VAT) and the parameters of oxidative stress, such as superoxide dismutase, enzyme glutathione reductase, and dimethylarginine, were measured, and the expression of protein oxidative damage product 3-nitro-tyrosine residues (nitrotyrosine) in VAT was identified with the use of immunohistochemistry. PCOS was associated with lower expression of GLUT4 and IRS1 and a higher level of oxidative stress in VAT, which was strongly correlated with WC and HOMA-IR. Presence of abdominal obesity further intensified the correlations observed in our measurements. The nitrotyrosine expression in VAT was stronger in PCOS patients. The strong correlation of insulin resistance with oxidative stress at the VAT level suggests that local oxidative stress and abnormalities of insulin signaling in adipose tissue play critical roles in the pathogenesis of PCOS. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. The severity of nocturnal hypoxia but not abdominal adiposity is associated with insulin resistance in non-obese men with sleep apnea.

    PubMed

    Borel, Anne-Laure; Monneret, Denis; Tamisier, Renaud; Baguet, Jean-Philippe; Faure, Patrice; Levy, Patrick; Halimi, Serge; Pépin, Jean-Louis

    2013-01-01

    Beyond obesity, sleep apnea syndrome is frequently associated with excess abdominal adiposity that could contribute to the deteriorated cardiometabolic risk profile of apneic patients. The present study addressed the respective contribution of the severity of sleep apnea syndrome and excess abdominal adiposity to the cardiometabolic risk profile of 38 non obese men with polysomnography-diagnosed sleep apnea syndrome (apnea-hypopnea index >15 events/hour). These otherwise healthy men performed a 75g-oral glucose tolerance test (OGTT) with plasma lipid/inflammatory and redox profiles. Twenty-one apneic men with high-waist circumference (>94 cm) were compared to 17 apneic men with low-waist circumference. Apneic men with high-waist circumference had higher AUC glucose and AUC insulin than apneic men with low-waist circumference. Accordingly, apneic men with high-waist circumference had higher hepatic insulin resistance as reflected by higher HOMA-resistance index, and lower global insulin sensitivity as reflected by lower insulin sensitivity index of Matsuda (derived from OGTT). The sleep structure and the apnea-hypopnea index were not different between the two groups. However, apneic men with high-waist circumference presented with lower mean nocturnal oxyhemoglobin (SpO2). In the 38 men, waist circumference and mean nocturnal SpO2 were inversely correlated (r = -0.43, p = 0.011) and were both associated with plasma glucose/insulin homeostasis indices: the higher the waist circumference, the lower the mean nocturnal SpO2, the lower the insulin-sensitivity. Finally, in multivariable regression model, mean nocturnal SpO2 and not waist circumference was associated with insulin-resistance. Thus, excess abdominal adiposity in non obese apneic men was associated with a deteriorated insulin-sensitivity that could be driven by a more severe nocturnal hypoxemia.

  8. The Severity of Nocturnal Hypoxia but Not Abdominal Adiposity Is Associated with Insulin Resistance in Non-Obese Men with Sleep Apnea

    PubMed Central

    Borel, Anne-Laure; Monneret, Denis; Tamisier, Renaud; Baguet, Jean-Philippe; Faure, Patrice; Levy, Patrick; Halimi, Serge; Pépin, Jean-Louis

    2013-01-01

    Background Beyond obesity, sleep apnea syndrome is frequently associated with excess abdominal adiposity that could contribute to the deteriorated cardiometabolic risk profile of apneic patients. Methods The present study addressed the respective contribution of the severity of sleep apnea syndrome and excess abdominal adiposity to the cardiometabolic risk profile of 38 non obese men with polysomnography-diagnosed sleep apnea syndrome (apnea-hypopnea index >15 events/hour). These otherwise healthy men performed a 75g-oral glucose tolerance test (OGTT) with plasma lipid/inflammatory and redox profiles. Twenty-one apneic men with high-waist circumference (>94 cm) were compared to 17 apneic men with low-waist circumference. Results Apneic men with high-waist circumference had higher AUC glucose and AUC insulin than apneic men with low-waist circumference. Accordingly, apneic men with high-waist circumference had higher hepatic insulin resistance as reflected by higher HOMA-resistance index, and lower global insulin sensitivity as reflected by lower insulin sensitivity index of Matsuda (derived from OGTT). The sleep structure and the apnea-hypopnea index were not different between the two groups. However, apneic men with high-waist circumference presented with lower mean nocturnal oxyhemoglobin (SpO2). In the 38 men, waist circumference and mean nocturnal SpO2 were inversely correlated (r = −0.43, p = 0.011) and were both associated with plasma glucose/insulin homeostasis indices: the higher the waist circumference, the lower the mean nocturnal SpO2, the lower the insulin-sensitivity. Finally, in multivariable regression model, mean nocturnal SpO2 and not waist circumference was associated with insulin-resistance. Conclusion Thus, excess abdominal adiposity in non obese apneic men was associated with a deteriorated insulin-sensitivity that could be driven by a more severe nocturnal hypoxemia. PMID:23951064

  9. Association of Oxidative Stress and Obesity with Insulin Resistance in Type 2 Diabetes Mellitus.

    PubMed

    Das, P; Biswas, S; Mukherjee, S; Bandyopadhyay, S K

    2016-01-01

    Oxidative stress occurs due to delicate imbalance between pro-oxidant and anti oxidant forces in our system. It has been found to be associated with many morbidities but its association with obesity and insulin resistance is still controversial. Here in our study we examined 167 patients of recent onset type 2 diabetes mellitus and 60 age sex matched non-diabetic control. Body Mass Index (BMI), abdominal circumference, fasting blood glucose, serum insulin and plasma Malondealdehyde (MDA, marker for oxidative stress) were measured in them. On the basis of BMI, subjects were divided into obese (BMI≥25) and non obese (BMI<25) groups. Insulin resistance scores were calculated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) method. Physical parameters (BMI, abdominal circumference) as well as levels of insulin and MDA were found to be significantly higher in subjects with diabetes than their non diabetic controls. The said parameters also showed significant difference in obese and non-obese sub groups. Insulin resistance score showed positive correlation with BMI, abdominal circumference, and plasma MDA, strength of association being highest with abdominal circumference. Plasma MDA was found to have positive correlation with physical parameters. Study concludes that, obesity mainly central type may predispose to insulin resistance and oxidative stress may be a crucial factor in its pathogenesis. Thus, oxidative stress may be the connecting link between obesity and type 2 diabetes mellitus, two on going global epidemics.

  10. Impact of weight loss with or without exercise on abdominal fat and insulin resistance in obese individuals: a randomised clinical trial.

    PubMed

    Trussardi Fayh, Ana Paula; Lopes, André Luiz; Fernandes, Pablo Rober; Reischak-Oliveira, Alvaro; Friedman, Rogério

    2013-08-28

    Evidence supports an important contribution of abdominal obesity and inflammation to the development of insulin resistance (IR) and CVD. Weight loss in obese individuals can reduce inflammation and, consequently, IR, but the role of training remains unclear. The aim of this study was to evaluate the effects of body weight reduction with and without exercise over abdominal fat tissue (primary outcome) and IR. In this randomised clinical trial, forty-eight obese individuals (age 31·8 (SD 6·0) years, BMI 34·8 (SD 2·7) kg/m2) were randomised to either a diet-only group (DI) or a diet and exercise group (DI þ EXE). Treatment was maintained until 5% of the initial body weight was lost. At baseline and upon completion, the following parameters were analysed: biochemical parameters such as glycaemia and insulin for the determination of homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP) and abdominal computed tomography for the determination of visceral and subcutaneous adipose tissue. A total of thirteen individuals dropped out before completing the weight-loss intervention and did not repeat the tests. In both the DI (n 18) and DI þ EXE (n 17) groups, we observed significant and similar decreases of visceral adipose tissue (difference between means: 7·9 (95% CI 29·5, 25·2) cm2, P¼0·36), hs-CRP (difference between means: 20·06 (95% CI 20·19, 0·03) mg/l, P¼0·39) and HOMA (difference between means: 20·04 (95% CI 20·17, 0·08), P¼0·53). In the present study, 5% weight loss reduced abdominal fat and IR in obese individuals and exercise did not add to the effect of weight loss on the outcome variables.

  11. Metabolic syndrome and insulin resistance in obese adolescents.

    PubMed

    Gobato, Amanda Oliva; Vasques, Ana Carolina J; Zambon, Mariana Porto; Barros Filho, Antonio de Azevedo; Hessel, Gabriel

    2014-03-01

    To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI), body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032) and with metabolic syndrome (p=0.006). All body composition indicators were correlated with insulin resistance (p<0.01). In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.

  12. Metabolic syndrome and insulin resistance in obese adolescents

    PubMed Central

    Gobato, Amanda Oliva; Vasques, Ana Carolina J.; Zambon, Mariana Porto; Barros, Antonio de Azevedo; Hessel, Gabriel

    2014-01-01

    Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI), body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032) and with metabolic syndrome (p=0.006). All body composition indicators were correlated with insulin resistance (p<0.01). In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance. PMID:24676191

  13. Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys: a randomized, controlled trial

    USDA-ARS?s Scientific Manuscript database

    The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown. We examined the effects of aerobic exercise (AE) versus resistance exercise (RE) without caloric restriction on abdominal adiposity, ectopic fat, and insulin sensitivity and se...

  14. Abdominal obesity as a mediator of the influence of physical activity on insulin resistance in Spanish adults.

    PubMed

    García-Hermoso, Antonio; Martínez-Vizcaíno, Vicente; Recio-Rodriguez, Jose I; Díez-Fernández, Ana; Gómez-Marcos, Manuel A; García-Ortiz, Luis

    2016-01-01

    The aim of the study was to analyze the relationship between moderate-to-vigorous physical activity (MVPA) and insulin resistance (IR) in Spanish adults and to examine whether this relationship is mediated by abdominal obesity (waist circumference - WC). The cross-sectional study included 1162 healthy subjects belonging to the EVIDENT study (mean age 55.0±13.3years; 61.8% women) from six different Spanish provinces. Moderate-to-vigorous physical activity (MVPA) was measured objectively over 7days using Actigraph accelerometers, collecting data in 60-second epochs, and retaining respondents with ≥4 valid days for the analysis. The homeostasis model of assessment (HOMA-IR) was used to determine IR, and its individual components - fasting glucose and insulin - were determined using standard protocols. Linear regression models were fitted according to Baron and Kenny's procedures for mediation analysis. Fasting insulin and HOMA-IR levels were significantly worse in adults who spent fewer minutes in MVPA (first quartile≤30.1 and 22.7min/day in men and women, respectively) after adjusting for age, sex, smoking habits, drinking habits, accelerometer wear time, sedentary time, and Mediterranean diet adherence. However, when WC was added to the ANCOVA models as a covariate, the effects disappeared. Mediation analysis reported that WC acts as a full mediator in the relationship between MVPA and IR (HOMA-IR and fasting insulin). These findings show that WC plays a pivotal role in the relationship between MVPA and IR, and therefore highlights that decreasing abdominal obesity might be considered as an intermediate outcome for evaluating interventions aimed at preventing diabetes mellitus. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Modified High-Sucrose Diet-Induced Abdominally Obese and Normal-Weight Rats Developed High Plasma Free Fatty Acid and Insulin Resistance

    PubMed Central

    Cao, Li; Liu, Xuehui; Cao, Hongyi; Lv, Qingguo; Tong, Nanwei

    2012-01-01

    Introduction. Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. Methods and Results. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. Conclusion. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle. PMID:23320128

  16. Modified high-sucrose diet-induced abdominally obese and normal-weight rats developed high plasma free fatty acid and insulin resistance.

    PubMed

    Cao, Li; Liu, Xuehui; Cao, Hongyi; Lv, Qingguo; Tong, Nanwei

    2012-01-01

    Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle.

  17. Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010

    PubMed Central

    Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K.; Kramer, Holly; Rosas, Sylvia E.; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L.

    2016-01-01

    Objective Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. Methods We analyzed data from the NHANES 1999–2010 for 6918 young adults ages 20–40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Results Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6–12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Conclusion Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease. PMID:27224643

  18. Preserved insulin sensitivity predicts metabolically healthy obese phenotype in children and adolescents.

    PubMed

    Vukovic, Rade; Milenkovic, Tatjana; Mitrovic, Katarina; Todorovic, Sladjana; Plavsic, Ljiljana; Vukovic, Ana; Zdravkovic, Dragan

    2015-12-01

    Available data on metabolically healthy obese (MHO) phenotype in children suggest that gender, puberty, waist circumference, insulin sensitivity, and other laboratory predictors have a role in distinguishing these children from metabolically unhealthy obese (MUO) youth. The goal of this study was to identify predictors of MHO phenotype and to analyze glucose and insulin metabolism during oral glucose tolerance test (OGTT) in MHO children. OGTT was performed in 244 obese children and adolescents aged 4.6-18.9 years. Subjects were classified as MHO in case of no fulfilled criterion of metabolic syndrome except anthropometry or as MUO (≥2 fulfilled criteria). Among the subjects, 21.7 % had MHO phenotype, and they were more likely to be female, younger, and in earlier stages of pubertal development, with lower degree of abdominal obesity. Insulin resistance was the only independent laboratory predictor of MUO phenotype (OR 1.59, CI 1.13-2.25), with 82 % sensitivity and 60 % specificity for diagnosing MUO using HOMA-IR cutoff point of ≥2.85. Although no significant differences were observed in glucose regulation, MUO children had higher insulin demand throughout OGTT, with 1.53 times higher total insulin secretion. Further research is needed to investigate the possibility of targeted treatment of insulin resistance to minimize pubertal cross-over to MUO in obese children. • Substantial proportion of the obese youth (21-68 %) displays a metabolically healthy (MHO) phenotype. • Gender, puberty, waist circumference, insulin sensitivity, and lower levels of uric acid and transaminases have a possible role in distinguishing MHO from metabolically unhealthy obese (MUO) children. • Insulin resistance was found to be the only significant laboratory predictor of MUO when adjusted for gender, puberty, and the degree of abdominal obesity. • Besides basal insulin resistance, MUO children were found to have a significantly higher insulin secretion throughout OGTT in

  19. Insulin resistance in obese children and adolescents.

    PubMed

    Romualdo, Monica Cristina dos Santos; Nóbrega, Fernando José de; Escrivão, Maria Arlete Meil Schimith

    2014-01-01

    To evaluate the presence of insulin resistance and its association with other metabolic abnormalities in obese children and adolescents. Retrospective study of 220 children and adolescents aged 5-14 years. Anthropometric measurements were performed (weight, height, and waist circumference) and clinical (gender, age, pubertal stage, and degree of obesity) and biochemical (glucose, insulin, total cholesterol, and fractions, triglycerides) data were analyzed. Insulin resistance was identified by the homeostasis model assessment for insulin resistance (HOMA-IR) index. The analysis of the differences between the variables of interest and the HOMA-IR quartiles was performed by ANOVA or Kruskal-Wallis tests. Insulin resistance was diagnosed in 33.20% of the sample. It was associated with low levels of high-density lipoprotein cholesterol (HDL-C; p=0.044), waist circumference measurement (p=0.030), and the set of clinical and metabolic (p=0.000) alterations. Insulin-resistant individuals had higher mean age (p=0.000), body mass index (BMI; p=0.000), abdominal circumference (p=0.000), median triglycerides (p=0.001), total cholesterol (p≤0.042), and low-density lipoprotein cholesterol (LDL-C; p≤0.027); and lower HDL-C levels (p=0.005). There was an increase in mean BMI (p=0.000), abdominal circumference (p=0.000), and median triglycerides (p=0.002) as the values of HOMA -IR increased, with the exception of HDL-C, which decreased (p=0.001). Those with the highest number of simultaneous alterations were between the second and third quartiles of the HOMA-IR index (p=0.000). The results confirmed that insulin resistance is present in many obese children and adolescents, and that this condition is associated with alterations that represent an increased risk for developing metabolic disorders in adulthood. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  20. [BO's abdominal acupuncture for obese type-2 diabetes mellitus].

    PubMed

    Yang, Yuan; Liu, Yunxia

    2015-04-01

    To observe the clinical efficacy of BO's abdominal acupuncture for obese type-2 diabetes mellitus (T2DM). Sixty patients of obese T2DM were randomly divided into an acupuncture group and a medication group, 30 cases in each one. Patients in the medication group were treated with basic treatment combined with oral administration of regular antidiabetics, three weeks as one session. Patients in the acupuncture group, based on the medication group, were treated with abdominal acupuncture at Yinqiguiyuan [Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6), Guanguan (CV 4)], Fusiguan [Huaroumen (ST 24), Wailing (TE 5)], Tianshu (ST 25), Daheng (SP 15), Qixue (KI 13), etc.; the treatment was given three times per week, 3 weeks as one session. The systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight, waist circumference (WC), hip circumference, body mass index (BI) were observed before and after treatment in the two groups, and fasting plasma glucose (FPG), fasting insulin (FINS), 2-hours postprandial blood glucose by oral glucose tolerance test (OGTT) and insulin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), HOMA-IR of insulin resistance index were calculated and adverge events were recorded. Compared before the treatment, SBP, WC, body weight, BMI, FPG, OG-TT2hBG, FINS, GTT2h insulin, HOMA-IR, TC and LDL-C in the acupuncture group were all significantly reduced (all P <0. 05), while FPG, OGTT2H insulin and TG were increased in the medication group (all P<0. 05)'. The differences of reducing SBP, WC, FPG, OGTT2H insulin, HOMA-IR, TC, TG and LDL-C were statistically significant between the two groups (all P<0. 05). The total effective rate was 93. 3% (28/30) in the acupuncture group, which was significantly superior to 23. 3% (7/30) in the medication group (P<0. 01). BO's abdominal acupuncture has obvious clinical efficacy for obese type-2 diabetes mellitus

  1. Short stature, abdominal obesity, insulin resistance and alterations in lipid profile in very low-income women living in Maceió, north-eastern Brazil.

    PubMed

    Florêncio, Telma T; Ferreira, Haroldo S; Cavalcante, Jairo C; Stux, Gabriela R; Sawaya, Ana L

    2007-04-01

    To test the hypothesis that short stature is associated with abdominal obesity, insulin resistance and lipid profile changes. Anthropometric data were collected from 237 women (18-60 years old), residents of a shantytown in Maceió. Biochemical profiles of 60 individuals drawn from this population were determined. Total and low-density lipoprotein (LDL) cholesterol levels and insulin resistance rose with increasing waist : hip circumference ratio, particularly in women. Short, overweight individuals exhibited larger biochemical alterations than overweight individuals of average stature. Short stature, when associated with overweight, is a risk factor for increased insulin resistance and alterations in lipid profile.

  2. Abdominal fat and insulin resistance in normal and overweight women: Direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM.

    PubMed

    Carey, D G; Jenkins, A B; Campbell, L V; Freund, J; Chisholm, D J

    1996-05-01

    Insulin resistance appears to be central to obesity, NIDDM, hyperlipidemia, and cardiovascular disease. While obese women with abdominal (android) fat distribution are more insulin resistant than those with peripheral (gynecoid) obesity, in nonobese women, the relationship between abdominal fat and insulin resistance is unknown. By measuring regional adiposity with dual-energy X-ray absorptiometry and insulin sensitivity by euglycemic-hyperinsulinemic clamp in 22 healthy women, with a mean +/- SE body BMI of 26.7 +/- 0.9 kg/m2 and differing risk factors for NIDDM, we found a strong negative relationship between central abdominal (intra-abdominal plus abdominal subcutaneous) fat and whole-body insulin sensitivity (r = -0.89, P < 0.0001) and nonoxidative glucose disposal (r = -0.77, P < 0.001), independent of total adiposity, family history of NIDDM, and past gestational diabetes. There was a large variation in insulin sensitivity, with a similar variation in central fat, even in those whose BMI was <25 kg/m2. Abdominal fat had a significantly stronger relationship with insulin sensitivity than peripheral nonabdominal fat (r2 = 0.79 vs. 0.44), and higher levels were associated with increased fasting nonesterified fatty acids, lipid oxidation, and hepatic glucose output. Because 79% of the variance in insulin sensitivity in this heterogeneous population was accounted for by central fat, abdominal adiposity appears to be a strong marker and may be a major determinant of insulin resistance in women.

  3. Insulin resistance, body composition, and fat distribution in obese children with nonalcoholic fatty liver disease.

    PubMed

    Yang, Hye Ran; Chang, Eun Jae

    2016-01-01

    The aim of this study was to evaluate the influence of body composition, especially distribution of body fat, and insulin resistance on nonalcoholic fatty liver disease (NAFLD) in obese children. One hundred obese children (66 boys, 34 girls) with (n=60) and without NAFLD (n=40) were assessed. Anthropometry, laboratory tests, abdominal ultrasonography, and dual energy x-ray absorption metry (DXA) were evaluated in all subjects. Subject age and measurements of liver enzymes, γ- glutamyl transpeptidase (γGT), uric acid, high-density lipoprotein cholesterol, and insulin resistance were significantly different between the non-NAFLD group and NAFLD group. Body fat and trunk fat percentage were significantly different between the two groups (p<0.001 and p=0.003), whereas extremity fat percentage was not (p=0.683). Insulin resistance correlated significantly with body fat and trunk fat percentages, age, liver enzymes, γGT, and uric acid in obese children. Multiple logistic regression analysis indicated that insulin resistance and trunk fat percentage significantly affected the development of NAFLD in obese children. Body fat, especially abdominal fat, influences the development of insulin resistance and subsequent NAFLD in obese children. Therefore, body composition measurement using DXA, in conjunction with biochemical tests, may be beneficial in evaluating obese children with NAFLD.

  4. Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns

    PubMed Central

    Papakyriakou, Panagiotis; Panagiotou, Themistoklis N.

    2015-01-01

    The prevalence of type 2 diabetes (T2D) is rapidly increasing. This is strongly related to the contemporary lifestyle changes that have resulted in increased rates of overweight individuals and obesity. Central (intra-abdominal) obesity is observed in the majority of patients with T2D. It is associated with insulin resistance, mainly at the level of skeletal muscle, adipose tissue and liver. The discovery of macrophage infiltration in the abdominal adipose tissue and the unbalanced production of adipocyte cytokines (adipokines) was an essential step towards novel research perspectives for a better understanding of the molecular mechanisms governing the development of insulin resistance. Furthermore, in an obese state, the increased cellular uptake of non-esterified fatty acids is exacerbated without any subsequent β-oxidation. This in turn contributes to the accumulation of intermediate lipid metabolites that cause defects in the insulin signaling pathway. This paper examines the possible cellular mechanisms that connect central obesity with defects in the insulin pathway. It discusses the discrepancies observed from studies organized in cell cultures, animal models and humans. Finally, it emphasizes the need for therapeutic strategies in order to achieve weight reduction in overweight and obese patients with T2D. PMID:26170839

  5. Adipose tissue oxygenation is associated with insulin sensitivity independently of adiposity in obese men and women.

    PubMed

    Goossens, Gijs H; Vogel, Max A A; Vink, Roel G; Mariman, Edwin C; van Baak, Marleen A; Blaak, Ellen E

    2018-04-23

    Adipose tissue (AT) dysfunction contributes to the pathophysiology of insulin resistance and type 2 diabetes. Previous studies have shown that altered AT oxygenation affects adipocyte functionality, but it remains to be elucidated whether altered AT oxygenation is more strongly related to obesity or insulin sensitivity. In the present study, we tested the hypothesis that AT oxygenation is associated with insulin sensitivity rather than adiposity in humans. Thirty-five lean and obese individuals (21 men and 14 women, aged 40-65 years) with either normal or impaired glucose metabolism participated in a cross-sectional single-centre study. We measured abdominal subcutaneous AT oxygenation, body composition and insulin sensitivity. AT oxygenation was higher in obese insulin resistant as compared to obese insulin sensitive (IS) individuals with similar age, body mass index and body fat percentage, both in men and women. No significant differences in AT oxygenation were found between obese IS and lean IS men. Moreover, AT oxygenation was positively associated with insulin resistance (r = 0.465; P = .005), even after adjustment for age, sex and body fat percentage (standardized β = 0.479; P = .005). In conclusion, abdominal subcutaneous AT oxygenation is associated with insulin sensitivity both in men and women, independently of adiposity. AT oxygenation may therefore be a promising target to improve insulin sensitivity. © 2018 John Wiley & Sons Ltd.

  6. Liver attenuation, pericardial adipose tissue, obesity, and insulin resistance: the Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    McAuley, Paul A; Hsu, Fang-Chi; Loman, Kurt K; Carr, J Jeffrey; Budoff, Matthew J; Szklo, Moyses; Sharrett, A Richey; Ding, Jingzhong

    2011-09-01

    Insulin resistance is linked to general and abdominal obesity, but its relation to hepatic lipid content and pericardial adipose tissue is less clear. The purpose of this study was to examine cross-sectional associations of liver attenuation, pericardial adipose tissue, BMI, and waist circumference with insulin resistance. We measured liver attenuation and pericardial adipose tissue using the existing cardiac computed tomography scans in 5,291 individuals free of clinical cardiovascular disease and diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA) during the study's baseline visit (2000-2002). Low liver attenuation was defined as the lowest quartile and high pericardial adipose tissue as the upper quartile of volume (cm(3)). We used standard clinical definitions for obesity and abdominal obesity. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA(IR)) index. In multivariate linear regression with all adiposity measures in the model simultaneously, all adiposity measures were significantly (P < 0.0001) associated with insulin resistance: regression coefficients (±s.e.) were 0.31 (±0.02) for low liver attenuation, 0.27 (±0.02) for high pericardial adipose tissue, 0.27 (±0.02) for obesity, and 0.32 (±0.02) for abdominal obesity. We found significant differences (P = 0.003) between standardized liver attenuation and insulin resistance by ethnicity: regression coefficients per 1 s.d. increment were 0.10 ± 0.01 for whites, 0.11 ± 0.02 for Chinese, 0.08 ± 0.2 for blacks, and 0.14 ± 0.01 for Hispanics. Liver attenuation and pericardial adipose tissue were associated with insulin resistance, independent of BMI and waist circumference.

  7. Abdominal obesity and metabolic syndrome: exercise as medicine?

    PubMed

    Paley, Carole A; Johnson, Mark I

    2018-01-01

    Metabolic syndrome is defined as a cluster of at least three out of five clinical risk factors: abdominal (visceral) obesity, hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) and insulin resistance. It is estimated to affect over 20% of the global adult population. Abdominal (visceral) obesity is thought to be the predominant risk factor for metabolic syndrome and as predictions estimate that 50% of adults will be classified as obese by 2030 it is likely that metabolic syndrome will be a significant problem for health services and a drain on health economies.Evidence shows that regular and consistent exercise reduces abdominal obesity and results in favourable changes in body composition. It has therefore been suggested that exercise is a medicine in its own right and should be prescribed as such. This review provides a summary of the current evidence on the pathophysiology of dysfunctional adipose tissue (adiposopathy). It describes the relationship of adiposopathy to metabolic syndrome and how exercise may mediate these processes, and evaluates current evidence on the clinical efficacy of exercise in the management of abdominal obesity. The review also discusses the type and dose of exercise needed for optimal improvements in health status in relation to the available evidence and considers the difficulty in achieving adherence to exercise programmes. There is moderate evidence supporting the use of programmes of exercise to reverse metabolic syndrome although at present the optimal dose and type of exercise is unknown. The main challenge for health care professionals is how to motivate individuals to participate and adherence to programmes of exercise used prophylactically and as a treatment for metabolic syndrome.

  8. [Abdominal obesity and coronary heart disease. Pathophysiology and clinical significance].

    PubMed

    Hauner, H

    1995-02-01

    The relationship between overweight and cardiovascular disease was a matter of debate for many years. Recent studies have demonstrated that obesity defined as body mass index of 30 kg/m2 or higher is associated with an exponential increase of cardiovascular complications. This effect is largely mediated by the induction of established risk factors such as dyslipidemia, hypertension and type 2 diabetes mellitus. Recently, there is growing evidence that the occurrence of most complications of obesity depends not only on the degree of overweight but also on the pattern of body fat distribution. Many data suggest that the anatomical localization of body fat is more important for the risk of developing complications than the adipose tissue mass per se. An abdominal, upper-body type of fat distribution, which can be easily determined by the measurement of waist and hip circumferences (waist/hip ratio = WHR), is also a confirmed risk factor for metabolic disturbances, hypertension and atherosclerosis, independent of body weight. However, the clinical appearance of these disturbances is frequently associated with the development of obesity. This network of metabolic disorders and their vascular complications is termed "metabolic syndrome" or "syndrome X" (Table 2). Abdominal obesity is now known to be closely associated with the metabolic syndrome and is regarded to represent its readily recognizable phenotypic feature. The components of the metabolic syndrome are characterized by varying forms and degrees of insulin resistance. It is assumed that insulin resistance, defined as diminished biological response to the action of insulin, represents the primary defect or at least the common pathogenetic link between these disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults

    PubMed Central

    Marina, Anna; Song, Xiaoling; Callahan, Holly S.; Kratz, Mario; Utzschneider, Kristina M.

    2017-01-01

    Purpose We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. Methods Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10: 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10: 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography. Results The rate of glucose disposal (Rd) during low-and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low: LFD: 0.12 ± 0.11 vs. HFD: −0.37 ± 0.15 mmol/min, mean ± SE, p < 0.01; Rdhigh: LFD: 0.11 ± 0.37 vs. HFD: −0.71 ± 0.26 mmol/ min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p < 0.01) with a trend on the HFD (r = 0.60, p = 0.07), whereas there was no association with intra-abdominal fat. The LFD led to an increase in VLDL palmitic (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) were strongly associated with changes in insulin sensitivity on both diets (LFD: r = −0.77; p < 0.01; HFD: r = −0.71; p = 0.02). Conclusions A diet very high in fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes. PMID:26615402

  10. Left ventricular function impairment in patients with normal-weight obesity: contribution of abdominal fat deposition, profibrotic state, reduced insulin sensitivity, and proinflammatory activation.

    PubMed

    Kosmala, Wojciech; Jedrzejuk, Diana; Derzhko, Roksolana; Przewlocka-Kosmala, Monika; Mysiak, Andrzej; Bednarek-Tupikowska, Grazyna

    2012-05-01

    Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. One hundred sixty-eight subjects (age, 38±7 years) with BMI <25kg/m(2) and no history of any disease affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (β=-0.17, P<0.006), C-reactive protein (β=-0.20, P<0.002) and abdominal fat deposit (β=-0.20, P<0.003); for tissue S velocity, PICP (β=-0.21, P<0.002) and abdominal fat deposit (β=-0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (β=-0.30, P<0.0001), PICP (β=-0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; β=-0.20, P<0.002); and for E/e'-PICP, IL-18 (both β=0.18, P<0.01) and HOMA IR (β=0.16, P<0.04). In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

  11. Endocannabinoid antagonism: blocking the excess in the treatment of high-risk abdominal obesity.

    PubMed

    Duffy, Danielle; Rader, Daniel

    2007-02-01

    Abdominal obesity is a prevalent, worldwide problem linked to cardiometabolic comorbidities and an increased risk of coronary heart disease. First-line therapy to reduce such risk revolves around diet and exercise; however, such changes are often difficult to implement and unsuccessful. Understanding the underlying pathophysiology of underlying metabolic derangements could provide new targets for pharmacologic therapy. One system that has gained recent attention is the endocannabinoid system. The endocannabinoid system has a significant role in central appetite control and peripheral lipogenesis and is up-regulated in diet-induced obesity. Rimonabant is a selective cannabinoid-1 receptor antagonist and is the first compound of its type to test the hypothesis that down-regulating an overactive endocannabinoid system could have therapeutic benefit not only for weight loss but also for the atherogenic dyslipidemia and insulin resistance that cluster with abdominal obesity in particular. Animal models have been critical for elucidating the role of the endocannabinoid system in obesity and in demonstrating that antagonism with rimonabant can induce loss of visceral fat and improve insulin sensitivity. Early human trials with rimonabant have confirmed significant reductions in weight, as well as favorable changes in atherogenic dyslipidemia, insulin resistance, and markers of inflammation. Interestingly, some of these beneficial metabolic effects are partially weight-loss-independent, confirming the importance of peripheral endocannabinoid system effects in addition to central effects.

  12. A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults.

    PubMed

    von Frankenberg, Anize D; Marina, Anna; Song, Xiaoling; Callahan, Holly S; Kratz, Mario; Utzschneider, Kristina M

    2017-02-01

    We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10: 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10: 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography. The rate of glucose disposal (Rd) during low- and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low: LFD: 0.12 ± 0.11 vs. HFD: -0.37 ± 0.15 mmol/min, mean ± SE, p < 0.01; Rd-high: LFD: 0.11 ± 0.37 vs. HFD: -0.71 ± 0.26 mmol/min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p < 0.01) with a trend on the HFD (r = 0.60, p = 0.07), whereas there was no association with intra-abdominal fat. The LFD led to an increase in VLDL palmitic (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) were strongly associated with changes in insulin sensitivity on both diets (LFD: r = -0.77; p < 0.01; HFD: r = -0.71; p = 0.02). A diet very high in fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes. CLINICALTRIALS. NCT00930371.

  13. Fatty Acid Content of Plasma Triglycerides May Contribute to the Heterogeneity in the Relationship Between Abdominal Obesity and the Metabolic Syndrome.

    PubMed

    Aristizabal, Juan C; Barona, Jacqueline; Gonzalez-Zapata, Laura I; Deossa, Gloria C; Estrada, Alejandro

    2016-08-01

    About one-third of the people with abdominal obesity do not exhibit the metabolic syndrome (MetS). Fatty acids in plasma triglycerides (TGs) may help to explain part of this heterogeneity. This study compared TG fatty acid profile of adults with and without abdominal obesity and examined the associations of these fatty acids with MetS components. Fifty-four abdominally obese subjects were matched by age and sex with 54 adults without abdominal obesity. People were classified with MetS according to the harmonizing criteria for MetS. Fatty acids in plasma TGs were analyzed by gas chromatography. There were no differences in fatty acids of plasma TGs between people with and without abdominal obesity. However, there were differences between abdominally obese people with and without MetS. The abdominally obese group with MetS had higher palmitic (+2.9%; P = 0.012) and oleic (+4.0%; P = 0.001) acids and lower linoleic (-6.4%; P = 0.018) and arachidonic (-1.2%; P = 0.004) acids. After adjustment for abdominal obesity, age, and sex, a stepwise regression analysis showed that palmitic acid positively contributed to the variance in insulin (β = +1.08 ± 1.01; P = 0.000) and homeostasis model assessment of insulin resistance (HOMA-IR) index (β = +1.09 ± 1.01; P = 0.000) and myristic acid positively contributed to the variance in systolic blood pressure (β = +1.09 ± 1.03; P = 0.006). In contrast, linoleic acid negatively contributed to the variance in glucose (β = -0.321 ± 0.09; P = 0.001) and high-sensitivity C-reactive protein (hsCRP; β = -1.05 ± 1.01; P = 0.000). There were no differences in the plasma TG fatty acid profile between people with and without abdominal obesity. Likewise, fatty acids in plasma TGs associated with many of the MetS variables independently of abdominal obesity. These results suggest that the plasma TG fatty acid profile may help to explain part of the heterogeneity

  14. Stress, abdominal obesity and intrarenal resistive index in essential hypertension.

    PubMed

    Trovato, G M; Pace, P; Martines, G F; Trovato, F M; Pirri, C; Catalano, D

    2012-07-01

    Although it is commonly believed that a strong causal link exists between psychological stress and hypertension, as well with other factors, such as obesity, just what kind of empirical evidence supports this assumption is still controversial. The aim of the study is to investigate if perceived stress have any interference with intrarenal resistance and hence with mechanisms related to Essential Hypertension (EH) and if Anxiety, Depression, Self efficacy and Illness Perception can account for perceived stress. Obesity, insulin resistance (HOMA), Doppler Renal Resistive Index (RRI) and glomerular filtration rate (GFR) are studied along with Psychological Stress Measure (PSM), Illness Perception Questionnaire (IPQ-R), Generalized Self-Efficacy scale (GSE) and Hospital Anxiety and Depression Scale (HADS) in 119 hypertensive patients referred for stable lasting EH, and 150 normal controls. Lower salt/lower calories Mediterranean diet, physical activity increase and smoking withdrawal counseling were provided. By Odds Ratios, higher risk of EH is associated with greater perceived stress, older age, lower GFR, obesity, greater RRI and insulin resistance. By Multiple Linear Regression the most significant variable that accounts for higher RRI are abdominal obesity and arterial pulse pressure; the only significant independent psychological variable that accounts for abdominal obesity are PSM and identity IPQ subscale. Self-Efficacy anxiety and Illness perception subscales (IPQr), accounts significantly for 62.0% of the variance to PSM, with possible effects on RRI and on the pathophysiological hypertension cascade. Worst identity and treatment control perceptions of EH, and a lower self-efficacy are the main psychological factors accounting for a greater stress. Interventions aimed to reduce perceived stress can be warranted in EH.

  15. Relationship of obesity and insulin resistance with the cerebrovascular reactivity: a case control study

    PubMed Central

    2014-01-01

    Background Obesity is associated with increased risk for stroke. The breath-holding index (BHI) is a measure of vasomotor reactivity of the brain which can be measured with the transcranial Doppler (TCD). We aim to evaluate obesity as an independent factor for altered cerebrovascular reactivity. Methods Cerebrovascular hemodynamics (mean flow velocities MFV, pulsatility index, PI, resistance index, RI, and BHI) was determined in 85 non-obese (Body Mass Index, BMI ≤27 kg/m2) and 85 obese subjects (BMI ≥35 kg/m2) without diabetes mellitus and hypertension. Anthropometric and metabolic variables, and scores to detect risk for obstructive sleep apnea (OSA) were analyzed for their association with the cerebrovascular reactivity. Results The BHI was significantly lower in subjects with obesity according to BMI and in subjects with abdominal obesity, but the PI and RI were not different between groups. There was a linear association between the BMI, the HOMA-IR, the Matsuda index, the waist circumference, and the neck circumference, with the cerebrovascular reactivity. After adjusting for insulin resistance, neck circumference, and abdominal circumference, obesity according to BMI was negatively correlated with the cerebrovascular reactivity. Conclusions We found a diminished vasomotor reactivity in individuals with obesity which was not explained by the presence of insulin resistance. PMID:24383894

  16. Abdominal obesity and hyperglycemia mask the effect of a common APOC3 haplotype on the risk of myocardial infarction.

    PubMed

    Ruiz-Narváez, Edward A; Sacks, Frank M; Campos, Hannia

    2008-06-01

    Plasma apolipoprotein (apo) C-III strongly predicts myocardial infarction (MI) and directly activates atherogenic processes in vascular cells. Genetic variation in the insulin response element of the APOC3 promoter is associated with an increased risk of MI. The objective was to determine whether the APOC3 promoter variation affects plasma apo C-III concentrations and MI only when insulin sensitivity is normal. The APOC3*222 haplotype, defined by the minor alleles of the single nucleotide polymorphisms 3238C-->G, -455T-->C, and -482C-->T, was studied in 1703 matched nonfatal case-control pairs with MI in the Central Valley of Costa Rica. We used fasting hyperglycemia and abdominal obesity as surrogates for insulin sensitivity. The APOC3*222 haplotype was associated with higher apo C-III concentrations only in those with the lowest waist circumference or fasting glucose concentration. The association between the APOC3*222 haplotype and nonfatal MI, previously reported in this population, was strongly influenced by fasting hyperglycemia and abdominal obesity. The odds ratios for MI for the APOC3*222 haplotype were 1.72 (95% CI: 1.16, 2.54) and 1.84 (1.31, 2.59) in subjects in the lowest quintiles of abdominal obesity and fasting hyperglycemia, respectively, and were 0.75 (0.54, 1.05) and 1.16 (0.85, 1.59) in subjects in the highest quintiles, respectively (P for interaction <0.05). The results support the concept that mutations in the APOC3 promoter inhibit the down-regulation of APOC3 expression by insulin. This cardioprotective system becomes dysfunctional in abdominal obesity and hyperglycemia.

  17. Determinants and definition of abdominal obesity as related to risk of diabetes, metabolic syndrome and coronary disease in Turkish men: a prospective cohort study.

    PubMed

    Onat, Altan; Uyarel, Hüseyin; Hergenç, Gülay; Karabulut, Ahmet; Albayrak, Sinan; Can, Günay

    2007-03-01

    We aimed to investigate determinants of abdominal obesity and its clinical impact on metabolic syndrome (MS), diabetes (DM) and coronary heart disease (CHD) in men. Prospective evaluation of 1638 male participants (aged 48.5+/-12.3), representative of Turkey's men who have a high prevalence of MS. For components of MS, criteria of NCEP guidelines were adopted, modified for abdominal obesity. Follow-up constituted 9650 person-years. Insulin level (relative risk [RR] 1.40 for doubling), C-reactive protein (CRP) and heavy smoking (protective) were independent predictors of newly developing abdominal obesity. High triglyceride and low HDL-cholesterol were significantly associated already with waist girth quartile II, apolipoprotein B with quartile III. Waist girth significantly predicted future MS from quartile II on, independent of insulin resistance (IR) by homeostatic model assessment, whereby its hazard ratio (HR, 2.6) exceeded double that of HOMA. CRP independently predicted MS. Age-adjusted HR of waist girth (1.59) was significant in predicting DM. Age- and smoking-adjusted top waist quartile conferred significant risk for incident CHD (RR 1.71) but not for overall mortality. As judged by sensitivity and specificity rates for future CHD, DM and MS, abdominal obesity was most appropriately defined with a waist girth of >or=95 cm, and an action level 1 of >or=87 cm was proposed for MS in this population. Serum insulin, CRP levels and (inversely) heavy smoking are predictors for abdominal obesity in Turkish men. Atherogenic dyslipidemia and elevated blood pressure are associated significantly already with modest rises in waist girth adjusted for age and smoking. Abdominal obesity shows substantial independence of IR in the development of MS. Increasing waist girth was predictive of MS, more strongly than of DM. Risk for CHD imparted by abdominal obesity is essentially mediated by risk factors it induces.

  18. Normal Weight but Low Muscle Mass and Abdominally Obese: Implications for the Cardiometabolic Risk Profile in Chronic Obstructive Pulmonary Disease.

    PubMed

    Beijers, Rosanne J H C G; van de Bool, Coby; van den Borst, Bram; Franssen, Frits M E; Wouters, Emiel F M; Schols, Annemie M W J

    2017-06-01

    It is well established that low muscle mass affects physical performance in chronic obstructive pulmonary disease (COPD). We hypothesize that combined low muscle mass and abdominal obesity may also adversely influence the cardiometabolic risk profile in COPD, even in those with normal weight. The cardiometabolic risk profile and the responsiveness to 4 months high-intensity exercise training was assessed in normal-weight patients with COPD with low muscle mass stratified by abdominal obesity. This is a cross-sectional study including 81 clinically stable patients with COPD (age 62.5 ± 8.2 years; 50.6% males; forced expiratory volume in 1 second 55.1 ± 19.5 percentage predicted) with fat-free mass index <25th percentile eligible for outpatient pulmonary rehabilitation. Body composition, blood biomarkers, blood pressure, physical activity level, dietary intake, and physical performance were assessed at baseline and in a subgroup after 4 months of exercise training. Mean body mass index was 22.7 ± 2.7 kg/m 2 , and 75% of patients had abdominal obesity. Abdominally obese patients had higher glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), branched chain amino acids and a higher prevalence of metabolic syndrome compared with those without abdominal obesity. Exercise training improved cycling endurance time and quadriceps strength, but did not yield a clinically meaningful improvement of the cardiometabolic risk profile. Triglycerides showed a significant decrease, while the HOMA-IR increased. Abdominal obesity is highly prevalent in normal-weight patients with COPD with low muscle mass who showed an increased cardiometabolic risk compared with patients without abdominal obesity. This cardiometabolic risk profile was not altered after 4 months of exercise training. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  19. IL-34 is associated with obesity, chronic inflammation, and insulin resistance.

    PubMed

    Chang, Eun-Ju; Lee, Seul Ki; Song, Young Sook; Jang, Yeon Jin; Park, Hye Soon; Hong, Joon Pio; Ko, A Ra; Kim, Dae Yeon; Kim, Jong-Hyeok; Lee, Yeon Ji; Heo, Yoon-Suk

    2014-07-01

    IL-34 is a recently identified alternative ligand for colony-stimulating factor-1 (CSF-1) receptor. IL-34 and CSF-1 are regulators of differentiation, proliferation, and survival in mononuclear phagocytes. Here, we investigated the IL-34 serum concentration and expression in human adipose tissues and any associations with insulin resistance. We recruited 19 nondiabetic obese women, 9 type 2 diabetic women, and 27 normal-weight women. Metabolic parameters, abdominal fat distribution, serum IL-34 concentration, and IL-34 mRNA expression were measured in abdominal sc adipose tissue (SAT) and visceral adipose tissue (VAT). In addition, the expression/secretion and putative effects of IL-34 were assessed in human differentiated adipocytes. Serum IL-34 concentration was measured before and 5 to 9 months after laparoscopic Roux-en-Y gastric bypass surgery was performed on the 20 obese patients. Regardless of diabetes status, obese patients demonstrated significantly higher serum IL-34 concentrations than controls. Serum IL-34 was significantly and positively correlated with insulin resistance-related metabolic parameters. IL-34 mRNA was significantly higher in VAT than SAT. IL-34 was expressed in adipocytes as well as nonadipocytes, and expression was significantly higher during adipogenesis. In differentiated adipocytes, the expression/secretion of IL-34 was enhanced by TNFα and IL-1β. In addition, IL-34 augmented fat accumulation and inhibited the stimulatory effects of insulin on glucose transport. Moreover, serum IL-34 was significantly decreased after Roux-en-Y gastric bypass-induced weight loss. The present study demonstrates, for the first time, that IL-34 is expressed in human adipose tissues and the circulating concentration is significantly elevated in obese patients. This suggests that IL-34 is associated with insulin resistance.

  20. Effects of clenbuterol on insulin resistance in conscious obese Zucker rats.

    PubMed

    Pan, S J; Hancock, J; Ding, Z; Fogt, D; Lee, M; Ivy, J L

    2001-04-01

    The present study was conducted to determine the effect of chronic administration of the long-acting beta(2)-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin. kg(-1). min(-1)) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.

  1. Abdominal obesity and circulating metabolites: A twin study approach.

    PubMed

    Bogl, Leonie H; Kaye, Sanna M; Rämö, Joel T; Kangas, Antti J; Soininen, Pasi; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Ortega-Alonso, Alfredo; Rissanen, Aila; Ala-Korpela, Mika; Kaprio, Jaakko; Pietiläinen, Kirsi H

    2016-03-01

    To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (rg) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference ≥3 kg/m(2)). Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (rg=0.40), glycoprotein (rg=0.37), serum triglycerides (rg=0.36), BCAAs (rg=0.30-0.40), HDL particle diameter (rg=-0.33) and HDL cholesterol (rg=-0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

    PubMed

    ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

    2015-12-01

    Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd <37.3 μmol kg(-1) min(-1) did not differ from insulin-sensitive obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), P<0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) (4.5±2.2 vs 2.7±1.4, P=0.004). Insulin-resistant obese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

  3. A Prospective Observational Study of Obesity, Body Composition, and Insulin Resistance in 18 Women With Bipolar Disorder and 17 Matched Control Subjects

    PubMed Central

    Fleet-Michaliszyn, Sara B.; Soreca, Isabella; Otto, Amy D.; Jakicic, John M.; Fagiolini, Andrea; Kupfer, David J.; Goodpaster, Bret H.

    2012-01-01

    Objective Patients with bipolar disorder are at increased risk for diabetes and cardiovascular diseases, possibly because of more severe insulin resistance. The primary purpose of this study was to determine whether insulin resistance is characteristic of bipolar disorder. Method The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was performed in 18 women with DSM-IV bipolar I disorder, and results were compared to those of 17 matched controls. Other risk factors were compared, including blood pressure, blood lipids, and abdominal obesity by computed tomography (CT). Additionally, substrate utilization was measured by indirect calorimetry, and free-living energy expenditure was estimated using wearable activity monitors. All data were collected between February 2006 and December 2007. Results Patients with bipolar disorder were no more insulin resistant than controls after accounting for generalized obesity (mean ± SEM HOMA-IR = 2.7 ± 0.7 vs. 2.5 ± 0.7, for patients and controls, respectively; p = .79). Although blood lipid profiles were generally similar in patients and controls, obese patients had higher blood pressure than controls. Obese patients had more mean ± SEM total abdominal fat (718.1 ± 35.1 cm2 vs. 607.4 ± 33.6 cm2: p = .04), and tended (p = .06) to have more visceral abdominal fat. Patients oxidized 13% less fat during resting conditions, although their resting metabolic rate was similar to that of controls. Conclusion Women with bipolar I disorder were no more insulin resistant than matched controls after accounting for their level of obesity. However, they were more hypertensive, had higher amounts of abdominal obesity, and had reduced rates of fat oxidation. Therefore, women with bipolar I disorder may be at a heightened risk for future weight gain and concomitant risk for diabetes and cardiovascular disease. PMID:19026257

  4. Prevalence of overweight, obesity, abdominal obesity and obesity-related risk factors in southern China.

    PubMed

    Hu, Lihua; Huang, Xiao; You, Chunjiao; Li, Juxiang; Hong, Kui; Li, Ping; Wu, Yanqing; Wu, Qinhua; Wang, Zengwu; Gao, Runlin; Bao, Huihui; Cheng, Xiaoshu

    2017-01-01

    The purpose of this study is to assess the prevalence of overweight/obesity, abdominal obesity and obesity-related risk factors in southern China. A cross-sectional survey of 15,364 participants aged 15 years and older was conducted from November 2013 to August 2014 in Jiangxi Province, China, using questionnaire forms and physical measurements. The physical measurements included body height, weight, waist circumference (WC), body fat percentage (BFP) and visceral adipose index (VAI). Multivariate logistic regression analysis was performed to evaluate the risk factors for overweight/obesity and abdominal obesity. The prevalence of overweight was 25.8% (25.9% in males and 25.7% in females), while that of obesity was 7.9% (8.4% in males and 7.6% in females). The prevalence of abdominal obesity was 10.2% (8.6% in males and 11.3% in females). The prevalence of overweight/obesity was 37.1% in urban residents and 30.2% in rural residents, and this difference was significant (P < 0.001). Urban residents had a significantly higher prevalence of abdominal obesity than rural residents (11.6% vs 8.7%, P < 0.001). Among the participants with an underweight/normal body mass index (BMI), 1.3% still had abdominal obesity, 16.1% had a high BFP and 1.0% had a high VAI. Moreover, among obese participants, 9.7% had a low /normal WC, 0.8% had a normal BFP and 15.9% had a normal VAI. Meanwhile, the partial correlation analysis indicated that the correlation coefficients between VAI and BMI, VAI and WC, and BMI and WC were 0.700, 0.666, and 0.721, respectively. A multivariate logistic regression analysis indicated that being female and having a high BFP and a high VAI were significantly associated with an increased risk of overweight/obesity and abdominal obesity. In addition, living in an urban area and older age correlated with overweight/obesity. This study revealed that obesity and abdominal obesity, which differed by gender and age, are epidemic in southern China. Moreover, there

  5. Abdominal obesity and hyperglycemia mask the effect of a common APOC3 haplotype on the risk of myocardial infarction123

    PubMed Central

    Ruiz-Narváez, Edward A; Sacks, Frank M; Campos, Hannia

    2013-01-01

    Background Plasma apolipoprotein (apo) C-III strongly predicts myocardial infarction (MI) and directly activates atherogenic processes invascularcells.Geneticvariationintheinsulinresponseelementofthe APOC3 promoter is associated with an increased risk of MI. Objective The objective was to determine whether the APOC3 promoter variation affects plasma apo C-III concentrations and MI only when insulin sensitivity is normal. Design TheAPOC3*222haplotype,definedbytheminorallelesofthe single nucleotide polymorphisms 3238C→G, –455T→C, and –482C→T, was studied in 1703 matched nonfatal case-control pairs with MI in the Central Valley of Costa Rica. We used fasting hyper-glycemia and abdominal obesity as surrogates for insulin sensitivity. Results The APOC3*222 haplotype was associated with higher apo C-III concentrations only in those with the lowest waist circumference or fasting glucose concentration. The association between the APOC3*222 haplotype and nonfatal MI, previously reported in this population, was strongly influenced by fasting hyperglycemia and abdominal obesity. The odds ratios for MI for the APOC3*222 haplotype were 1.72 (95% CI: 1.16, 2.54) and 1.84 (1.31, 2.59) in subjects in the lowest quintiles of abdominal obesity and fasting hyperglycemia, respectively, and were 0.75 (0.54, 1.05) and 1.16 (0.85, 1.59) in subjects in the highest quintiles, respectively (P for interaction <0.05). Conclusion The results support the concept that mutations in the APOC3 promoter inhibit the down-regulation of APOC3 expression by insulin. This cardioprotective system becomes dysfunctional in abdominal obesity and hyperglycemia. PMID:18541587

  6. Skeletal muscle ceramide species in men with abdominal obesity.

    PubMed

    de la Maza, M P; Rodriguez, J M; Hirsch, S; Leiva, L; Barrera, G; Bunout, D

    2015-04-01

    Obesity is a risk factor for diabetes and its consequences, including accelerated ageing and mortality. The underlying factor could be accumulation of certain lipid moieties, such as ceramides (CER) and diacylgycerol (DAG) within muscle tissue, which are known to promote insulin resistance (IR), induce inflammation and oxidative injury, ultimately altering muscle function. First, to study the relationship between body composition and age (independent variables) with skeletal muscle accumulation of lipid species, oxidative injury and strength. Second, to analyze the relationship between muscle tissue metabolites and insulin resistance, inflammation and lymphocyte telomere length, the latter as an indicator of ageing. The sample included 56 healthy sedentary males, scheduled for inguinal hernia surgery, aged 27 to 80 y. Each individual was subject to anthropometric measurements, body composition assessment through radiologic densitometry (DEXA), measurement of handgrip and quadriceps strength, serum biochemical parameters (lipoproteins, creatinine, high sensitivity C reactive protein [hsCRP], fasting and post glucose insulin and glucose concentrations for calculation of IR through the Matsuda and HOMA-IR indexes), and extraction of peripheral leukocytes for measurement of telomere length. During the surgical procedure, a sample of muscle tissue was obtained (anterior abdominal oblique) in order to measure CER and DAG (and sub species according to chain length and saturation) by mass spectrometry, 4 hydroxy-2-nonenal adducts (4-HNE) using electron microscopy immunohistochemistry, and carboxymethyl-lisine (CML) by immunohistochemistry, the latter as indicators of oxidative stress (OS). Body mass index (BMI) of twenty six individuals was > 25 k/m2, while BMI of 7 was > 30 k/m2. Overweight/obese individuals, did not exhibit differences in skeletal muscle lipid metabolites, however total CER and specific long chain CER sub-species (20 and 22 carbon) increased

  7. Prevalence of overweight, obesity, abdominal obesity and obesity-related risk factors in southern China

    PubMed Central

    Hu, Lihua; Huang, Xiao; You, Chunjiao; Li, Juxiang; Hong, Kui; Li, Ping; Wu, Yanqing; Wu, Qinhua; Wang, Zengwu; Gao, Runlin; Bao, Huihui

    2017-01-01

    Objectives The purpose of this study is to assess the prevalence of overweight/obesity, abdominal obesity and obesity-related risk factors in southern China. Methods A cross-sectional survey of 15,364 participants aged 15 years and older was conducted from November 2013 to August 2014 in Jiangxi Province, China, using questionnaire forms and physical measurements. The physical measurements included body height, weight, waist circumference (WC), body fat percentage (BFP) and visceral adipose index (VAI). Multivariate logistic regression analysis was performed to evaluate the risk factors for overweight/obesity and abdominal obesity. Results The prevalence of overweight was 25.8% (25.9% in males and 25.7% in females), while that of obesity was 7.9% (8.4% in males and 7.6% in females). The prevalence of abdominal obesity was 10.2% (8.6% in males and 11.3% in females). The prevalence of overweight/obesity was 37.1% in urban residents and 30.2% in rural residents, and this difference was significant (P < 0.001). Urban residents had a significantly higher prevalence of abdominal obesity than rural residents (11.6% vs 8.7%, P < 0.001). Among the participants with an underweight/normal body mass index (BMI), 1.3% still had abdominal obesity, 16.1% had a high BFP and 1.0% had a high VAI. Moreover, among obese participants, 9.7% had a low /normal WC, 0.8% had a normal BFP and 15.9% had a normal VAI. Meanwhile, the partial correlation analysis indicated that the correlation coefficients between VAI and BMI, VAI and WC, and BMI and WC were 0.700, 0.666, and 0.721, respectively. A multivariate logistic regression analysis indicated that being female and having a high BFP and a high VAI were significantly associated with an increased risk of overweight/obesity and abdominal obesity. In addition, living in an urban area and older age correlated with overweight/obesity. Conclusion This study revealed that obesity and abdominal obesity, which differed by gender and age, are

  8. Factors associated with abdominal obesity in children

    PubMed Central

    Melzer, Matheus Ribeiro Theodósio Fernandes; Magrini, Isabella Mastrangi; Domene, Semíramis Martins Álvares; Martins, Paula Andrea

    2015-01-01

    Objective: To identify the association of dietary, socioeconomic factors, sedentary behaviors and maternal nutritional status with abdominal obesity in children. Methods: A cross-sectional study with household-based survey, in 36 randomly selected census tracts in the city of Santos, SP. 357 families were interviewed and questionnaires and anthropometric measurements were applied in mothers and their 3-10 years-old children. Assessment of abdominal obesity was made by maternal and child's waist circumference measurement; for classification used cut-off points proposed by World Health Organization (1998) and Taylor et al. (2000) were applied. The association between variables was performed by multiple logistic regression analysis. Results: 30.5% of children had abdominal obesity. Associations with children's and maternal nutritional status and high socioeconomic status were shown in the univariate analysis. In the regression model, children's body mass index for age (OR=93.7; 95%CI 39.3-223.3), female gender (OR=4.1; 95%CI 1.8-9.3) and maternal abdominal obesity (OR=2.7; 95%CI 1.2-6.0) were significantly associated with children's abdominal obesity, regardless of the socioeconomic status. Conclusions: Abdominal obesity in children seems to be associated with maternal nutritional status, other indicators of their own nutritional status and female gender. Intervention programs for control of childhood obesity and prevention of metabolic syndrome should consider the interaction of the nutritional status of mothers and their children. PMID:26298655

  9. [Factors associated with abdominal obesity in children].

    PubMed

    Melzer, Matheus Ribeiro Theodósio Fernandes; Magrini, Isabella Mastrangi; Domene, Semíramis Martins Álvares; Martins, Paula Andrea

    2015-12-01

    To identify the association of dietary, socioeconomic factors, sedentary behaviors and maternal nutritional status with abdominal obesity in children. A cross-sectional study with household-based survey, in 36 randomly selected census tracts in the city of Santos/SP. 357 families were interviewed and questionnaires and anthropometric measurements were applied in mothers and their 3-0 years-old children. Assessment of abdominal obesity was made by maternal and child's waist circumference measurement; for classification used cut-off points proposed by World Health Organization (1998) and Taylor et al. (2000) were applied. The association between variables was performed by multiple logistic regression analysis. 30.5% of children had abdominal obesity. Associations with children's and maternal nutritional status and high socioeconomic status were shown in the univariate analysis. In the regression model, children's body mass index for age (OR=93.7; 95%CI 39.3-223.3), female gender (OR=4.1; 95%CI 1.8-9.3) and maternal abdominal obesity (OR=2.7; 95%CI 1.2-6.0) were significantly associated with children's abdominal obesity, regardless of the socioeconomic status. Abdominal obesity in children seems to be associated with maternal nutritional status, other indicators of their own nutritional status and female gender. Intervention programs for control of childhood obesity and prevention of metabolic syndrome should consider the interaction of the nutritional status of mothers and their children. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. The effect of abdominal obesity in patients with polycystic ovary syndrome on metabolic parameters.

    PubMed

    Franik, G; Bizoń, A; Włoch, S; Pluta, D; Blukacz, Ł; Milnerowicz, H; Madej, P

    2017-11-01

    Polycystic ovarian syndrome and obesity contribute to the metabolic complications for women of reproductive age. The aim of present study was to analyze the effect of abdominal obesity expressed using waist/hip ratio (WHR) in patients with polycystic ovary syndrome on metabolic parameters. The study included 659 women with PCOS with WHR <0.8 and ≥0.8 aged between 17 and 44 years. Patients were tested for follicular stimulating hormone, luteinizing hormone, 17-beta-estradiol, dehydroepiandrosterone sulfate, androstenedione, sex hormone binding globulin, and total lipid profile during the follicular phase (within 3 and 5 days of their menstrual cycle). Also, fasting glucose and insulin concentrations, and after, oral-glucose glucose administration, were determinate. De Ritis and Castelli index I and II were calculated. Women with WHR ≥0.8 had higher concentration of glucose and  insulin (both fasting and after 120 min of oral administration of 75 g glucose), as well as HOMA-IR value, than women with WHR value < 0.8. Also, abdominal obesity disorders hormonal parameters. Higher free androgen index and lower concentration of sex hormone binding globulin and dehydroepiandrosterone sulfate were found in female with WHR ≥ 0.8. Follicular stimulating hormone, luteinizing hormone, androstenedione, and 17-beta-estradiol, were on similar level in both groups. Elevation in triglycerides, total cholesterol, and low-density lipoprotein levels, as well as decrease in high density lipoprotein level in serum of women with WHR value ≥ 0.8, were found when compared to women with WHR < 0.8. A statistically significant correlation was found between WHR value and glucose, insulin, sex hormone binding globulin, free androgen index and lipid profile parameters. Abdominal obesity causes additional disorders in metabolic and hormonal parameters in PCOS women, which confirmed changes in analyzed parameters between PCOS women with WHR < 0.8 and WHR ≥ 0.8 and statistically

  11. Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents.

    PubMed

    Juárez-López, Carlos; Klünder-Klünder, Miguel; Medina-Bravo, Patricia; Madrigal-Azcárate, Adrián; Mass-Díaz, Eliezer; Flores-Huerta, Samuel

    2010-06-07

    Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents. An analytical, cross-sectional and population-based study was performed in forty-four public primary schools in Campeche City, Mexico. A total of 466 obese children and adolescents between 11-13 years of age were recruited. Fasting glucose and insulin concentrations, high density lipoprotein cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressures were measured; insulin resistance and metabolic syndrome were also evaluated. Out of the total population studied, 69% presented low values of high density lipoprotein cholesterol, 49% suffered from abdominal obesity, 29% had hypertriglyceridemia, 8% presented high systolic and 13% high diastolic blood pressure, 4% showed impaired fasting glucose, 51% presented insulin resistance and 20% metabolic syndrome. In spite of being obese, 13% of the investigated population did not present any metabolic disorder. For each one of the components of the metabolic syndrome, when insulin resistance increased so did odds ratios as cardiometabolic risk factors. Regardless of age and gender an increased degree of insulin resistance is associated with a higher prevalence of disorders in each of the components of the metabolic syndrome and with a heightened risk of suffering metabolic syndrome among obese children and adolescents.

  12. Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss.

    PubMed

    Hoenig, M; Thomaseth, K; Waldron, M; Ferguson, D C

    2007-01-01

    Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.

  13. Insulin resistance in obesity as the underlying cause for the metabolic syndrome.

    PubMed

    Gallagher, Emily J; Leroith, Derek; Karnieli, Eddy

    2010-01-01

    The metabolic syndrome affects more than a third of the US population, predisposing to the development of type 2 diabetes and cardiovascular disease. The 2009 consensus statement from the International Diabetes Federation, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity, and the National Heart, Lung, and Blood Institute defines the metabolic syndrome as 3 of the following elements: abdominal obesity, elevated blood pressure, elevated triglycerides, low high-density lipoprotein cholesterol, and hyperglycemia. Many factors contribute to this syndrome, including decreased physical activity, genetic predisposition, chronic inflammation, free fatty acids, and mitochondrial dysfunction. Insulin resistance appears to be the common link between these elements, obesity and the metabolic syndrome. In normal circumstances, insulin stimulates glucose uptake into skeletal muscle, inhibits hepatic gluconeogenesis, and decreases adipose-tissue lipolysis and hepatic production of very-low-density lipoproteins. Insulin signaling in the brain decreases appetite and prevents glucose production by the liver through neuronal signals from the hypothalamus. Insulin resistance, in contrast, leads to the release of free fatty acids from adipose tissue, increased hepatic production of very-low-density lipoproteins and decreased high-density lipoproteins. Increased production of free fatty acids, inflammatory cytokines, and adipokines and mitochondrial dysfunction contribute to impaired insulin signaling, decreased skeletal muscle glucose uptake, increased hepatic gluconeogenesis, and β cell dysfunction, leading to hyperglycemia. In addition, insulin resistance leads to the development of hypertension by impairing vasodilation induced by nitric oxide. In this review, we discuss normal insulin signaling and the mechanisms by which insulin resistance contributes to the development of the metabolic

  14. Dissecting the relationship between obesity and hyperinsulinemia: Role of insulin secretion and insulin clearance.

    PubMed

    Kim, Mee Kyoung; Reaven, Gerald M; Kim, Sun H

    2017-02-01

    The aim of this study was to better delineate the complex interrelationship among insulin resistance (IR), secretion rate (ISR), and clearance rate (ICR) to increase plasma insulin concentrations in obesity. Healthy volunteers (92 nondiabetic individuals) had an insulin suppression test to measure IR and graded-glucose infusion test to measure ISR and ICR. Obesity was defined as a body mass index (BMI) ≥30 kg/m 2 , and IR was defined as steady-state plasma glucose (SSPG) ≥10 mmol/L during the insulin suppression test. Plasma glucose and insulin concentrations, ISR, and ICR were compared in three groups: insulin sensitive/overweight; insulin sensitive/obesity; and insulin resistant/obesity. Compared with the insulin-sensitive/overweight group, the insulin-sensitive/obesity had significantly higher insulin area under the curve (AUC) and ISR AUC during the graded-glucose infusion test (P < 0.001). Glucose AUC and ICR were similar. The insulin-resistant/obesity group had higher insulin AUC and ISR AUC compared with the insulin-sensitive/obesity but also had higher glucose AUC and decreased ICR (P < 0.01). In multivariate analysis, both BMI and SSPG were significantly associated with ISR. Plasma insulin concentration and ISR are increased in individuals with obesity, irrespective of degree of IR, but a decrease in ICR is confined to the subset of individuals with IR. © 2016 The Obesity Society.

  15. Physical activity and abdominal obesity in youth.

    PubMed

    Kim, YoonMyung; Lee, SoJung

    2009-08-01

    Childhood obesity continues to escalate despite considerable efforts to reverse the current trends. Childhood obesity is a leading public health concern because overweight-obese youth suffer from comorbidities such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, metabolic syndrome, and cardiovascular disease, conditions once considered limited to adults. This increasing prevalence of chronic health conditions in youth closely parallels the dramatic increase in obesity, in particular abdominal adiposity, in youth. Although mounting evidence in adults demonstrates the benefits of regular physical activity as a treatment strategy for abdominal obesity, the independent role of regular physical activity alone (e.g., without calorie restriction) on abdominal obesity, and in particular visceral fat, is largely unclear in youth. There is some evidence to suggest that, independent of sedentary activity levels (e.g., television watching or playing video games), engaging in higher-intensity physical activity is associated with a lower waist circumference and less visceral fat. Several randomized controlled studies have shown that aerobic types of exercise are protective against age-related increases in visceral adiposity in growing children and adolescents. However, evidence regarding the effect of resistance training alone as a strategy for the treatment of abdominal obesity is lacking and warrants further investigation.

  16. Fatty liver disease, glucose tolerance and insulin resistance in obese adolescents.

    PubMed

    Slyper, A H; Rosenberg, H; Kabra, A; Huang, W-M; Blech, B; Matsumura, M M

    2015-12-01

    Adult studies suggest that intra-hepatic fat predicts 2-h blood glucose levels and type 2 diabetes, and may have a role in the development of insulin resistance. Our study objective was to explore relationships between intra-hepatic fat and (i) blood glucose levels and (ii) insulin resistance determined by homeostasis model assessment (HOMA) in a group of obese adolescents. Subjects were 61 obese non-diabetic male and female volunteers aged 12-18 years inclusive with a body mass index >95th percentile for age and 2-h blood glucose <200 mg dL(-1) . Each subject underwent 2-h glucose tolerance testing and measurement of haemoglobin A1c, ultrasensitive C-reactive protein and fasting insulin. Visceral, subcutaneous abdominal and intra-hepatic fat were determined by magnetic resonance imaging. Intra-hepatic fat was measured by gradient echo chemical shift imaging. Alanine aminotransferase levels and hepatic phase difference were not significant correlates of fasting or 2-h glucose. In a multiple regression model including hepatic phase difference and visceral fat volume, visceral fat volume was the sole predictor of HOMA. This study provides no support to the notion that intra-hepatic fat has a role in the regulation of fasting blood glucose, 2-h postprandial blood glucose or systemic insulin resistance. © 2014 World Obesity.

  17. Inhibition of 11β-hydroxysteroid dehydrogenase type 1 ameliorates obesity-related insulin resistance.

    PubMed

    Shao, Shiying; Zhang, Xiaojie; Zhang, Muxun

    2016-09-09

    Excess 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be implicated in the development of obesity related metabolic disorders. The present study measured the expression level of 11β-HSD1 in visceral adipose tissues from 23 patients undergoing abdominal operation. Correlation of 11β-HSD1 expression with BMI, waist-to-hip ratio (WHR), HOMA-IR, and serum lipids was evaluated by spearman correlation analysis. High-fat diet-induced obese (DIO) rats were orally dosed with BVT.2733 for 4 weeks. Weight, plasma insulin, and lipids were detected at the end of the treatment. The effects of 11β-HSD1 inhibition on the key insulin-signaling cascade and adipocytokines were measured by western blot and ELISA respectively. 11β-HSD1 was increased in patients with central obesity, the expression level of which was closely related with WHR (r = 0.5851), BMI (r = 0.4952), and HOMA-IR (r = 0.4637). Obesity related insulin resistance in high-fat DIO rats, as reflected by a marked decrease in IRS-1, IRS-2, GLUT4, and PI3K, could be attenuated by 11β-HSD1 inhibition. Furthermore, the down-regulation of 11β-HSD1 could correct the disordered profiles of adipocytokines including adiponectin, IL-6, and TNF-α. These findings indicated that 11β-HSD1 inhibition can give a potential benefit in reducing obesity and lowering insulin resistance by modulating the insulin-signaling pathway and adipocytokine production. Copyright © 2016. Published by Elsevier Inc.

  18. Evidence in obese children: contribution of hyperlipidemia, obesity-inflammation, and insulin sensitivity.

    PubMed

    Chang, Chi-Jen; Jian, Deng-Yuan; Lin, Ming-Wei; Zhao, Jun-Zhi; Ho, Low-Tone; Juan, Chi-Chang

    2015-01-01

    Evidence shows a high incidence of insulin resistance, inflammation and dyslipidemia in adult obesity. The aim of this study was to assess the relevance of inflammatory markers, circulating lipids, and insulin sensitivity in overweight/obese children. We enrolled 45 male children (aged 6 to 13 years, lean control = 16, obese = 19, overweight = 10) in this study. The plasma total cholesterol, HDL cholesterol, triglyceride, glucose and insulin levels, the circulating levels of inflammatory factors, such as TNF-α, IL-6, and MCP-1, and the high-sensitive CRP level were determined using quantitative colorimetric sandwich ELISA kits. Compared with the lean control subjects, the obese subjects had obvious insulin resistance, abnormal lipid profiles, and low-grade inflammation. The overweight subjects only exhibited significant insulin resistance and low-grade inflammation. Both TNF-α and leptin levels were higher in the overweight/obese subjects. A concurrent correlation analysis showed that body mass index (BMI) percentile and fasting insulin were positively correlated with insulin resistance, lipid profiles, and inflammatory markers but negatively correlated with adiponectin. A factor analysis identified three domains that explained 74.08% of the total variance among the obese children (factor 1: lipid, 46.05%; factor 2: obesity-inflammation, 15.38%; factor 3: insulin sensitivity domains, 12.65%). Our findings suggest that lipid, obesity-inflammation, and insulin sensitivity domains predominantly exist among obese children. These factors might be applied to predict the outcomes of cardiovascular diseases in the future.

  19. Dietary fiber, plasma insulin, and obesity.

    PubMed

    Albrink, M J

    1978-10-01

    The relationship between obesity, insulin resistance, and hyperinsulinemia is briefly reviewed. The possibility is considered that excess insulin secretion is the cause rather than the result of insulin resistance and obesity. Glucose administration is one of the most frequently studied of those factors known to stimulate insulin secretion. Much less well documented is the fact that meals of equal protein, fat, and carbohydrate content may cause different responses of plasma glucose and insulin. An experiment is reported in which the effects of a high-carbohydrate, high-fiber meal administered to seven healthy young adults were compared with the effects of a meal equally high in carbohydrate but composed largely of glucose in liquid formula form. The high-fiber meal caused an insulin rise less than half that caused by the liquid formula meal although the plasma glucose response to the two meals was not significantly different. The hypothesis is proposed that a high-carbohydrate, fiber-depleted diet, high in simple sugars, by repeatedly stimulating an excessive insulin response, may lead to insulin resistance and obesity in susceptible individuals and may play a role in the common occurrence of obesity in industrialized societies.

  20. Prevalence of overweight, obesity, abdominal-obesity and short stature of adult population of Rosario, Argentina.

    PubMed

    Zapata, María Elisa; Bibiloni, María Del Mar; Tur, Josep A

    2016-09-20

    The aim of this work was to assess the prevalence of overweight, obesity, abdominal-obesity and short stature among Rosario (Argentina) adult population. A cross-sectional nutritional survey was carried out in Rosario (2012-2013). A random sample (n = 1194) of adult population (18-70 years old) was interviewed. Anthropometric measurements and a general questionnaire incorporating questions related to socio-demographic and lifestyle characteristics, education level and physical activity were used. The current study detected a high prevalence of overweight and obesity among adult population in Rosario. The prevalence of overweight was 32.7% (43.9% in men and 27.6% in women, p < 0.001), of obesity was 23.5% (21.6% in men and 24.3% in women), and of abdominal obesity was 57.5% (63.5% in men vs.54.8% in women, p < 0.005). Multivariate analysis showed that the prevalence of overweight/obesity and abdominal obesity increased according the age and abdominal obesity decreased with high physical activity in men. In women prevalence of overweight/obesity, and abdominal obesity increased with age, marital status (married or coupled), presence of at least one child at home and low educational level. The prevalence of short stature was higher in women (16.4% vs. 8.4%, p < 0.001) and was related with age, overweight and abdominal obesity.

  1. Effects of Endogenous Androgens and Abdominal Fat Distribution on the Interrelationship Between Insulin and Non-Insulin-Mediated Glucose Uptake in Females

    PubMed Central

    Ezeh, Uche; Pall, Marita; Mathur, Ruchi; Dey, Damini; Berman, Daniel; Chen, Ida Y.; Dumesic, Daniel A.

    2013-01-01

    Background: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance. Glucose disposal occurs via noninsulin-mediated glucose uptake (NIMGU) and insulin-mediated glucose uptake (IMGU). It is unknown whether in PCOS NIMGU increases to compensate for declining IMGU and whether androgens and fat distribution influence this relationship. Objectives: The objective of the study was to compare in women with PCOS and controls the interrelationship between NIMGU [ie, glucose effectiveness (Sg)] and IMGU [ie, the insulin sensitivity index (Si)] and the role of androgens and fat distribution. Participants: Twenty-eight PCOS (by National Institutes of Health 1990 criteria) and 28 control (age, race, and body mass index matched) women were prospectively studied. A subset of 16 PCOS subjects and 16 matched controls also underwent abdominal computed tomography. Main Outcome Measures: Glucose disposal (by a frequently sampled iv glucose tolerance test), circulating androgens, and abdominal fat distribution [by waist to hip ratio and visceral (VAT) and sc (SAT) adipose tissue content] were measured. Results: PCOS women had lower mean Si and similar Sg and abdominal fat distribution compared with controls. PCOS women with Si below the PCOS median (more insulin resistant) had a lower mean Sg than controls with Si above the control median (more insulin sensitive). In PCOS only, body mass index, free T, modified Ferriman-Gallwey score, and waist to hip ratio independently predicted Sg, whereas Si did not. In PCOS, VAT and SAT independently and negatively predicted Si and Sg, respectively. Conclusion: The decreased IMGU in PCOS is not accompanied by a compensatory increase in NIMGU or associated with excessive VAT accumulation. Increased general obesity, SAT, and hyperandrogenism are primary predictors of the deterioration of NIMGU in PCOS. PMID:23450052

  2. Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat.

    PubMed

    Goldsmith, Felicia; Guice, Justin; Page, Ryan; Welsh, David A; Taylor, Christopher M; Blanchard, Eugene E; Luo, Meng; Raggio, Anne M; Stout, Rhett W; Carvajal-Aldaz, Diana; Gaither, Amanda; Pelkman, Christine; Ye, Jianping; Martin, Roy J; Geaghan, James; Durham, Holiday A; Coulon, Diana; Keenan, Michael J

    2017-01-01

    To determine if whole-grain (WG) flour with resistant starch (RS) will produce greater fermentation than isolated RS in obese Zucker Diabetic Fatty (ZDF) rats, and whether greater fermentation results in different microbiota, reduced abdominal fat, and increased insulin sensitivity. This study utilized four groups fed diets made with either isolated digestible control starch, WG control flour (6.9% RS), isolated RS-rich corn starch (25% RS), or WG corn flour (25% RS). ZDF rats fermented RS and RS-rich WG flour to greatest extent among groups. High-RS groups had increased serum glucagon-like peptide 1 (GLP-1) active. Feeding isolated RS showed greater Bacteroidetes to Firmicutes phyla among groups, and rats consuming low RS diets possessed more bacteria in Lactobacillus genus. However, no differences in abdominal fat were observed, but rats with isolated RS had greatest insulin sensitivity among groups. Data demonstrated ZDF rats (i) possess a microbiota that fermented RS, and (ii) WG high-RS fermented better than purified RS. However, fermentation and microbiota changes did not translate into reduced abdominal fat. The defective leptin receptor may limit ZDF rats from responding to increased GLP-1 and different microbiota for reducing abdominal fat, but did not prevent improved insulin sensitivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Determinants of High Fasting Insulin and Insulin Resistance Among Overweight/Obese Adolescents.

    PubMed

    Ling, Jerri Chiu Yun; Mohamed, Mohd Nahar Azmi; Jalaludin, Muhammad Yazid; Rampal, Sanjay; Zaharan, Nur Lisa; Mohamed, Zahurin

    2016-11-08

    Hyperinsulinaemia is the earliest subclinical metabolic abnormality, which precedes insulin resistance in obese children. An investigation was conducted on the potential predictors of fasting insulin and insulin resistance among overweight/obese adolescents in a developing Asian country. A total of 173 overweight/obese (BMI > 85 th percentile) multi-ethnic Malaysian adolescents aged 13 were recruited from 23 randomly selected schools in this cross-sectional study. Waist circumference (WC), body fat percentage (BF%), physical fitness score (PFS), fasting glucose and fasting insulin were measured. Insulin resistance was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). Adjusted stepwise multiple regression analysis was performed to predict fasting insulin and HOMA-IR. Covariates included pubertal stage, socioeconomic status, nutritional and physical activity scores. One-third of our adolescents were insulin resistant, with girls having significantly higher fasting insulin and HOMA-IR than boys. Gender, pubertal stage, BMI, WC and BF% had significant, positive moderate correlations with fasting insulin and HOMA-IR while PFS was inversely correlated (p < 0.05). Fasting insulin was primarily predicted by gender-girls (Beta = 0.305, p < 0.0001), higher BMI (Beta = -0.254, p = 0.02) and greater WC (Beta = 0.242, p = 0.03). This study demonstrated that gender, BMI and WC are simple predictors of fasting insulin and insulin resistance in overweight/obese adolescents.

  4. Multiorgan insulin sensitivity in lean and obese subjects.

    PubMed

    Conte, Caterina; Fabbrini, Elisa; Kars, Marleen; Mittendorfer, Bettina; Patterson, Bruce W; Klein, Samuel

    2012-06-01

    To provide a comprehensive assessment of multiorgan insulin sensitivity in lean and obese subjects with normal glucose tolerance. The hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions was performed in 40 obese (BMI 36.2 ± 0.6 kg/m(2), mean ± SEM) and 26 lean (22.5 ± 0.3 kg/m(2)) subjects with normal glucose tolerance. Insulin was infused at different rates to achieve low, medium, and high physiological plasma concentrations. In obese subjects, palmitate and glucose R(a) in plasma decreased with increasing plasma insulin concentrations. The decrease in endogenous glucose R(a) was greater during low-, medium-, and high-dose insulin infusions (69 ± 2, 74 ± 2, and 90 ± 2%) than the suppression of palmitate R(a) (52 ± 4, 68 ± 1, and 79 ± 1%). Insulin-mediated increase in glucose disposal ranged from 24 ± 5% at low to 253 ± 19% at high physiological insulin concentrations. The suppression of palmitate R(a) and glucose R(a) were greater in lean than obese subjects during low-dose insulin infusion but were the same in both groups during high-dose insulin infusion, whereas stimulation of glucose R(d) was greater in lean than obese subjects across the entire physiological range of plasma insulin. Endogenous glucose production and adipose tissue lipolytic rate are both very sensitive to small increases in circulating insulin, whereas stimulation of muscle glucose uptake is minimal until high physiological plasma insulin concentrations are reached. Hyperinsulinemia within the normal physiological range can compensate for both liver and adipose tissue insulin resistance, but not skeletal muscle insulin resistance, in obese people who have normal glucose tolerance.

  5. Quantification of Abdominal Fat in Obese and Healthy Adolescents Using 3 Tesla Magnetic Resonance Imaging and Free Software for Image Analysis.

    PubMed

    Eloi, Juliana Cristina; Epifanio, Matias; de Gonçalves, Marília Maia; Pellicioli, Augusto; Vieira, Patricia Froelich Giora; Dias, Henrique Bregolin; Bruscato, Neide; Soder, Ricardo Bernardi; Santana, João Carlos Batista; Mouzaki, Marialena; Baldisserotto, Matteo

    2017-01-01

    Computed tomography, which uses ionizing radiation and expensive software packages for analysis of scans, can be used to quantify abdominal fat. The objective of this study is to measure abdominal fat with 3T MRI using free software for image analysis and to correlate these findings with anthropometric and laboratory parameters in adolescents. This prospective observational study included 24 overweight/obese and 33 healthy adolescents (mean age 16.55 years). All participants underwent abdominal MRI exams. Visceral and subcutaneous fat area and percentage were correlated with anthropometric parameters, lipid profile, glucose metabolism, and insulin resistance. Student's t test and Mann-Whitney's test was applied. Pearson's chi-square test was used to compare proportions. To determine associations Pearson's linear correlation or Spearman's correlation were used. In both groups, waist circumference (WC) was associated with visceral fat area (P = 0.001 and P = 0.01 respectively), and triglycerides were associated with fat percentage (P = 0.046 and P = 0.071 respectively). In obese individuals, total cholesterol/HDL ratio was associated with visceral fat area (P = 0.03) and percentage (P = 0.09), and insulin and HOMA-IR were associated with visceral fat area (P = 0.001) and percentage (P = 0.005). 3T MRI can provide reliable and good quality images for quantification of visceral and subcutaneous fat by using a free software package. The results demonstrate that WC is a good predictor of visceral fat in obese adolescents and visceral fat area is associated with total cholesterol/HDL ratio, insulin and HOMA-IR.

  6. [Excess weight and abdominal obesity in Galician children and adolescents].

    PubMed

    Pérez-Ríos, Mónica; Santiago-Pérez, María Isolina; Leis, Rosaura; Martínez, Ana; Malvar, Alberto; Hervada, Xurxo; Suanzes, Jorge

    2017-12-06

    The excess of weight, mainly obesity, during childhood and adolescence increases morbimortality risk in adulthood. The aim of this article is to estimate both the overall prevalence, as well as according to age and gender, of underweight, overweight, obesity and abdominal obesity among schoolchildren aged between 6-15-years-old in the school year 2013-2014. Data were taken from a cross-sectional community-based study carried out on a representative sample, by gender and age, of the Galician population aged between 6 and 15 years-old. The prevalence of underweight, overweight, and obese children (Cole's cut-off criteria) and abdominal obesity (Taylor's cut-off criteria) were estimated after performing objective measurements of height, weight and waist circumference at school. A total of 7,438 students were weighed and measured in 137 schools. The prevalence of overweight and obese individuals was 24.9% and 8.2%, respectively. The prevalence of abdominal obesity was 25.8%, with 4% of children with normal weight having abdominal obesity. These data highlight the need to promote primary prevention measures at early ages in order to decrease the occurrence of the premature onset of disease in the future. The prevalence of excess weight is underestimated if abdominal obesity is not taken into consideration. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  7. Predictors of urinary incontinence between abdominal obesity and non-obese male adults.

    PubMed

    Li, Dongmei; Xu, Yi; Nie, Qingbin; Li, Yan; Mao, Gengsheng

    2017-09-01

    To investigate factors that may be associated with urinary incontinence (UI) in abdominal obese and non-obese adult males. Data were analyzed for 2671 men (≥40 years of age) who participated in the National Health and Nutrition Examination Survey (2005-2008). We define abdominal obesity as a waist circumference >102 cm. Men with Incontinence Severity Index ≥3 were defined as having UI. Logistic regression analyses were used to identify factors associated with stress and urge UI. Multivariate analysis found that in abdominal obese men, stress UI was associated with enlarged prostate (odds ratio [OR] = 2.20, 95% confidence interval [CI]: 1.16-4.16), chronic respiratory tract disease (OR = 2.78, 95% CI: 1.55-4.97), and major depression (OR = 4.79, 95% CI: 1.79-12.84). In non-obese men, arthritis was associated with stress UI (odds ratio = 3.37, 95% CI: 1.06-10.73). Urge UI in abdominally obese men was associated with age ≥65 years (OR = 1.67, 95% CI: 1.05-2.67), being non-Hispanic black (OR = 1.63, 95% CI: 1.06-2.52), and with enlarged prostate (OR = 2.30, 95% CI: 1.54-3.40), arthritis (OR = 1.39, 95% CI: 1.03-1.88), and major depression (OR = 2.96, 95% CI: 1.89-4.64). Urge UI in non-obese men was associated with current smoking (OR = 1.79, 95% CI: 1.01-3.17), major depression (OR = 2.60, 95% CI: 1.33-5.09) and vitamin D deficiency (OR = 1.61, 95% CI: 1.01-2.59). Factors associated with urinary incontinence varied with abdominal obesity status and type of UI. The findings identify important contributors to urinary incontinence that clinicians should consider to help manage and effectively treat the condition.

  8. Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome.

    PubMed

    Gambineri, Alessandra; Patton, Laura; De Iasio, Rosaria; Cantelli, Barbara; Cognini, Graciela Estela; Filicori, Marco; Barreca, Antonina; Diamanti-Kandarakis, Evanthia; Pagotto, Uberto; Pasquali, Renato

    2005-07-01

    Somatostatin reduces LH, GH, and insulin, and somatostatin receptors are present at the ovarian level; somatostatin analogs are thus potential candidates for treatment of the polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate the effect of octreotide-LAR, a long-acting somatostatin analog, in anovulatory abdominal obese women with PCOS. A single-blind, placebo-controlled study was performed, lasting for 7 months. The patients were ambulatory throughout the study. Twenty PCOS subjects were enrolled. Eighteen completed the study. A low-calorie diet was given during the first month, a low-calorie diet plus octreotide-LAR (10 mg; n = 10 subjects) or placebo (n = 10 subjects) was then given, with one im injection every 28 d (for 6 months). The main outcome measures were clinical features, computerized tomography measurement of fat distribution, androgens, GH, IGF-I, IGF-binding proteins (IGFBPs), fasting and glucose-stimulated insulin, and ovulation. Octreotide had no additional effect in reducing body fat or improving fat distribution than placebo. Conversely, octreotide produced an additional decrease in fasting (P = 0.018) and glucose-stimulated (P = 0.038) insulin levels, an increase in IGFBP-2 (P = 0.042) and IGFBP-3 (P = 0.047), and an improvement in hirsutism (P = 0.004). Moreover, a trend toward greater reductions in testosterone (P = 0.061) and androstenedione (P = 0.069) was observed in women treated with octreotide-LAR compared with those given placebo. All women treated with octreotide ovulated at the end of the study compared with only one of those receiving placebo (P < 0.001). Octreotide-LAR may be usefully applied to hypocalorically dieting, abdominal obese PCOS women to improve hyperandrogenism and the insulin-IGF-I system. Restoration of ovulatory menstrual cycles appears to be another advantage of this treatment.

  9. Vegetarian diet reduces the risk of hypertension independent of abdominal obesity and inflammation: a prospective study.

    PubMed

    Chuang, Shao-Yuan; Chiu, Tina H T; Lee, Chun-Yi; Liu, Ting-Ting; Tsao, Chwen Keng; Hsiung, Chao A; Chiu, Yen-Feng

    2016-11-01

    A vegetarian diet may prevent elevation of blood pressures and lower the risk for hypertension through lower degrees of obesity, inflammation, and insulin resistance. This study investigated the association between a vegetarian diet and hypertension incidence in a cohort of Taiwanese adult nonsmokers and examined whether this association was mediated through inflammation, abdominal obesity, or insulin resistance (using fasting glucose as a proxy). This matched cohort study was from the 1994-2008 MJ Health Screening Database. Each vegetarian was matched with five nonvegetarians by age, sex, and study site. The analysis included 4109 nonsmokers (3423 nonvegetarians and 686 vegetarians), followed for a median of 1.61 years. The outcome includes hypertension incidence, as well as SBP and DBP levels. Regression analysis was performed to assess the association between vegetarian diet and hypertension incidence or future blood pressure levels in the presence/absence of potential mediators. Vegetarians had a 34% lower risk for hypertension, adjusting for age and sex (odds ratio: 0.66, 95% confidence interval: 0.50-0.87; SBP: -3.3 mmHg, P < 0.001; DBP: -1.5 mmHg, P < 0.001). The results stay statistically significant after further adjustment for C-reactive protein, waist circumference, and fasting glucose (odds ratio: 0.72, 95% confidence interval: 0.55-0.86; SBP: -2.4 mmHg, P < 0.05; DBP: -1.1 mmHg, P < 0.05). The protective association between vegetarian diet and hypertension appeared to be consistent across age groups. Taiwanese vegetarians had lower incidence of hypertension than nonvegetarians. Vegetarian diets may protect against hypertension beyond lower abdominal obesity, inflammation, and insulin resistance.

  10. Abdominal obesity and mortality risk among men in nineteenth-century North America.

    PubMed

    Kahn, H S; Williamson, D F

    1994-10-01

    The health consequences of an adverse body-fat distribution (e.g., android, upper-body, visceral) have only recently concerned the medical community. Ninety years ago, however, actuarial study demonstrated the relationship of body-fat distribution to the mortality experience of insured, North American men. Thirty-four insurance companies pooled their data on males issued life policies between 1870 and 1899. Special classes of risk were defined by weight for height at baseline or by the observation that abdominal girth exceeded the girth of the expanded chest (abdominal obesity). The mortality experience of each risk class was compared to an age-stratified, actuarial table of the period. We present new analyses of these historical data relating specifically to the mortality impact of abdominal obesity. Among 163,567 overweight men, the prevalence of abdominal obesity increased with age and with degree of overweight. Among moderately overweight men, those with abdominal obesity experienced 133% of the expected mortality rate compared to 112% of the expected mortality for those who were not abdominally obese. Severely overweight men with abdominal obesity experienced 152% of the expected mortality compared to 135% of the expected mortality for severely overweight men who were not abdominally obese. We believe this nineteenth-century, acturial study of waist and chest girths was the first demonstration that body-fat distribution can influence longevity. These early actuarial findings, taken with more recent reports, establish that abdominal enlargement, but not necessarily an 'upper-body' fat distribution, constitutes a major health hazard. Future research must establish which abdominal-obesity index best predicts disease outcomes.

  11. Partly replacing meat protein with soy protein alters insulin resistance and blood lipids in postmenopausal women with abdominal obesity.

    PubMed

    van Nielen, Monique; Feskens, Edith J M; Rietman, Annemarie; Siebelink, Els; Mensink, Marco

    2014-09-01

    Increasing protein intake and soy consumption appear to be promising approaches to prevent metabolic syndrome (MetS). However, the effect of soy consumption on insulin resistance, glucose homeostasis, and other characteristics of MetS is not frequently studied in humans. We aimed to investigate the effects of a 4-wk, strictly controlled, weight-maintaining, moderately high-protein diet rich in soy on insulin sensitivity and other cardiometabolic risk factors. We performed a randomized crossover trial of 2 4-wk diet periods in 15 postmenopausal women with abdominal obesity to test diets with 22 energy percent (En%) protein, 27 En% fat, and 50 En% carbohydrate. One diet contained protein of mixed origin (mainly meat, dairy, and bread), and the other diet partly replaced meat with soy meat analogues and soy nuts containing 30 g/d soy protein. For our primary outcome, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at the end of both periods. Plasma total, LDL, and HDL cholesterol, triglycerides, glucose, insulin, and C-reactive protein were assessed, and blood pressure, arterial stiffness, and intrahepatic lipid content were measured at the start and end of both periods. Compared with the mixed-protein diet, the soy-protein diet resulted in greater insulin sensitivity [FSIGT: insulin sensitivity, 34 ± 29 vs. 22 ± 17 (mU/L)(-1) · min(-1), P = 0.048; disposition index, 4974 ± 2543 vs. 2899 ± 1878, P = 0.038; n = 11]. Total cholesterol was 4% lower after the soy-protein diet than after the mixed-protein diet (4.9 ± 0.7 vs. 5.1 ± 0.6 mmol/L, P = 0.001), and LDL cholesterol was 9% lower (2.9 ± 0.7 vs. 3.2 ± 0.6 mmol/L, P = 0.004; n = 15). Thus, partly replacing meat with soy in a moderately high-protein diet has clear advantages regarding insulin sensitivity and total and LDL cholesterol. Therefore, partly replacing meat products with soy products could be important in preventing MetS. This trial was registered at clinicaltrials

  12. Relationships of occupational and non-occupational physical activity to abdominal obesity.

    PubMed

    Steeves, J A; Bassett, D R; Thompson, D L; Fitzhugh, E C

    2012-01-01

    Physically active occupations may protect against the risk of abdominal obesity. This study assessed the interaction between non-occupational physical activity (NOA) (leisure-time, transport and domestic activity) and occupational activity (OA) in relation to abdominal obesity. A total of 3539 adults over the age of 20, with no work limitations, employed in one of the 17 occupations classified as low OA (LOA) or high OA (HOA) were identified in the 1999-2004 National Health and Nutrition Examination Survey. Waist circumference (WC) was used to categorize individuals into either non-obese or abdominally obese (WC>88 cm in women and >102 cm in men) categories. NOA was divided into three categories based upon physical activity guidelines: (1) no NOA; (2) insufficient NOA; and (3) sufficient NOA. Logistic regression was used to examine possible associations between NOA, OA and abdominal obesity. In those who are sedentary outside of work, a high-activity occupation reduces the odds risk ratio of being categorized with abdominal obesity to 0.37 in comparison with those who work in low-activity occupations. For people working in low-activity occupations, there was a clear association with activity outside of work and the odds risk ratio of being categorized with abdominal obesity. In these adults, a reduced odds ratio was found only among those who met the physical activity guidelines through NOA (odds ratio=0.55; 95% confidence interval (CI)=0.40-0.75). HOA is associated with a reduced risk of abdominal obesity. Thus, it is important to include OA in studies seeking to understand the association between physical activity and abdominal adiposity.

  13. Obesity, abdominal obesity, physical activity, and caloric intake in US adults: 1988 to 2010.

    PubMed

    Ladabaum, Uri; Mannalithara, Ajitha; Myer, Parvathi A; Singh, Gurkirpal

    2014-08-01

    Obesity and abdominal obesity are associated independently with morbidity and mortality. Physical activity attenuates these risks. We examined trends in obesity, abdominal obesity, physical activity, and caloric intake in US adults from 1988 to 2010. Univariate and multivariate analyses were performed using National Health and Nutrition Examination Survey data. Average body mass index (BMI) increased by 0.37% (95% confidence interval [CI], 0.30-0.44) per year in both women and men. Average waist circumference increased by 0.37% (95% CI, 0.30-0.43) and 0.27% (95% CI, 0.22-0.32) per year in women and men, respectively. The prevalence of obesity and abdominal obesity increased substantially, as did the prevalence of abdominal obesity among overweight adults. Younger women experienced the greatest increases. The proportion of adults who reported no leisure-time physical activity increased from 19.1% (95% CI, 17.3-21.0) to 51.7% (95% CI, 48.9-54.5) in women, and from 11.4% (95% CI, 10.0-12.8) to 43.5% (95% CI, 40.7-46.3) in men. Average daily caloric intake did not change significantly. BMI and waist circumference trends were associated with physical activity level but not caloric intake. The associated changes in adjusted BMIs were 8.3% (95% CI, 6.9-9.6) higher among women and 1.7% (95% CI, 0.68-2.8) higher among men with no leisure-time physical activity compared with those with an ideal level of leisure-time physical activity. Our analyses highlight important dimensions of the public health problem of obesity, including trends in younger women and in abdominal obesity, and lend support to the emphasis placed on physical activity by the Institute of Medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Obesity, Abdominal Obesity, Physical Activity, and Caloric Intake in U.S. Adults: 1988-2010

    PubMed Central

    Ladabaum, Uri; Mannalithara, Ajitha; Myer, Parvathi A.; Singh, Gurkirpal

    2014-01-01

    Background Obesity and abdominal obesity are independently associated with morbidity and mortality. Physical activity attenuates these risks. We examined trends in obesity, abdominal obesity, physical activity, and caloric intake in U.S. adults from 1988 to 2010. Methods Univariate and multivariate analyses were performed using National Health and Nutrition Examination Survey (NHANES) data. Results Average body-mass index (BMI) increased by 0.37% (95% CI, 0.30-0.44%) per year in both women and men. Average waist circumference increased by 0.37% (95% CI, 0.30-0.43%) and 0.27% (95% CI, 0.22-0.32%) per year in women and men, respectively. The prevalence of obesity and abdominal obesity increased substantially, as did the prevalence of abdominal obesity among overweight adults. Younger women experienced the greatest increases. The proportion of adults who reported no leisure-time physical activity increased from 19.1% (95% CI, 17.3-21.0%) to 51.7% (95% CI, 48.9-54.5%) in women, and from 11.4% (95% CI, 10.0-12.8%) to 43.5% (95% CI, 40.7-46.3%) in men. Average daily caloric intake did not change significantly. BMI and waist circumference trends were associated with physical activity level, but not caloric intake. The associated changes in adjusted BMIs were 8.3% (95% CI, 6.9-9.6%) higher among women and 1.7% (95% CI, 0.68-2.8%) higher among men with no leisure-time physical activity compared to those with an ideal level of leisure-time physical activity. Conclusions Our analyses highlight important dimensions of the public health problem of obesity, including trends in younger women and in abdominal obesity, and lend support to the emphasis placed on physical activity by the Institute of Medicine. PMID:24631411

  15. Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance.

    PubMed

    Baranova, Ancha; Gowder, Shobha J; Schlauch, Karen; Elariny, Hazem; Collantes, Rochelle; Afendy, Arian; Ong, Janus P; Goodman, Zachary; Chandhoke, Vikas; Younossi, Zobair M

    2006-09-01

    Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.

  16. Relationship of abdominal obesity with cardiovascular disease, diabetes and hyperlipidaemia in Spain.

    PubMed

    Casanueva, Felipe F; Moreno, Basilio; Rodríguez-Azeredo, Rosario; Massien, Christine; Conthe, Pedro; Formiguera, Xavier; Barrios, Vivencio; Balkau, Beberly

    2010-07-01

    To evaluate the relevance of obesity and abdominal obesity in the prevalence of cardiovascular disease (CVD), diabetes mellitus, hyperlipidaemia and hypertension in primary care patients and to ascertain whether waist circumference (WC) measurement should be included in routine clinical practice in addition to body mass index (BMI). As part of the IDEA study, primary care physicians from Spain recruited patients aged 18-80 years. WC and BMI and the presence of CVD, diabetes mellitus, hyperlipidaemia and hypertension were recorded. Finally, 17 980 were analysed. An age-related increase in adiposity was observed. Overall 33% were obese by BMI, and 51% of subjects presented abdominal obesity by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) (WC > 102 cm for men and > 88 cm for women). Although there was a correlation between BMI and WC, they presented different distribution patterns. Women, but not men, with a high level of education, professional activity and smoking were associated with a lower WC. Abdominal obesity was significantly associated with CVD. Some subjects with abdominal obesity but lean by BMI, showed an increased prevalence of CVD and diabetes. Furthermore, abdominal obesity was strongly associated with dyslipidaemia and hypertension. Half of the primary care patients studied showed abdominal obesity as measured by WC, whereas one-third was obese by BMI. Abdominal obesity was strongly associated with CVD and diabetes, even in patients lean by BMI. WC should be included in the routine clinical practice in addition to BMI.

  17. Dietary patterns and their associations with general obesity and abdominal obesity among young Chinese women.

    PubMed

    Zhang, J G; Wang, Z H; Wang, H J; Du, W W; Su, C; Zhang, J; Jiang, H R; Zhai, F Y; Zhang, B

    2015-09-01

    Dietary patterns represent the combined effects of foods and efficaciously illustrate the impact of diet on health outcomes. This study identified the dietary patterns and determined their relationships with obesity among young Chinese women. In 2011, the China Health and Nutrition Survey included 2363 young women aged 18-44 years. Factor analysis of data from three consecutive 24-h dietary recalls identified the dietary patterns. Weight, height and waist circumstance (WC) were measured, and body mass index (BMI) was calculated. General obesity was defined as BMI ⩾28 kg/m(2) and abdominal obesity as WC ⩾85 cm. Four dietary patterns were identified: traditional south; traditional north; snack; and high protein. After adjusting for confounders and energy intake, women in the highest-score quintiles of the traditional south pattern were less likely to have general obesity (odds ratio (OR)=0.48; 95% confidence interval (CI) 0.29-0.78) and abdominal obesity (OR=0.64; 95% CI 0.46-0.90). Subjects in the highest-score quintiles of the traditional north pattern had significantly greater risk of general obesity (OR=2.28; 95% CI 1.38-3.74) and of abdominal obesity (OR=2.32; 95% CI 1.66-3.24). The traditional south pattern of rice as the major staple food with pork and vegetable dishes is associated with lower risk of general and abdominal obesity. The traditional north pattern of high intake of wheat, other cereals and tubers is positively associated with general and abdominal obesity. This provides important information for interventions and policies addressing obesity prevention among young Chinese women.

  18. Prevalence of Overweight, Obesity, and Abdominal Obesity among Urban Saudi Adolescents: Gender and Regional Variations

    PubMed Central

    Abahussain, Nada A.; Al-Sobayel, Hana I.; Qahwaji, Dina M.; Alsulaiman, Nouf A.; Musaiger, Abdulrahman O.

    2014-01-01

    ABSTRACT The nutrition transition with associated lifestyle-related non-communicable diseases has rapidly reached many developing countries, including Saudi Arabia. Therefore, the objective of this study was to examine the prevalence of overweight, obesity, and abdominal obesity among Saudi adolescents. This school-based multicentre cross-sectional study was conducted during 2009-2010 in three major cities in Saudi Arabia: Al-Khobar, Jeddah, and Riyadh. Participants included 2,908 students of secondary schools (1,401 males and 1,507 females) aged 14 to 19 years, randomly selected using a multistage stratified cluster-sampling technique. Weight, height, and waist-circumference were measured; prevalence of overweight and obesity was determined using age- and sex-specific BMI cutoff reference standards of the International Obesity Task Force (IOTF). Abdominal obesity was determined using waist-to-height ratio (WHtR) cutoffs (above 0.5). The prevalence of overweight was 19.5% in males and 20.8% in females while that of obesity was 24.1% in males and 14% in females. The prevalence of abdominal obesity in males and females was 35.9% and 30.3% respectively. Higher prevalence of obesity was observed among adolescents in private schools. Across all ages, overweight and obesity ranged from 39.9% to 45.6% in males and from 30.4% to 38.7% in females. ANCOVA, controlling for age, showed significant interaction effects (city by gender). It is concluded that the proportions of overweight, obesity, and abdominal obesity, observed among Saudi adolescents were remarkably high. Such high prevalence of overweight and obesity is a major public-health concern. PMID:25895197

  19. Gender, alexithymia and physical inactivity associated with abdominal obesity in type 1 diabetes mellitus: a cross sectional study at a secondary care hospital diabetes clinic.

    PubMed

    Melin, Eva O; Svensson, Ralph; Thunander, Maria; Hillman, Magnus; Thulesius, Hans O; Landin-Olsson, Mona

    2017-01-01

    Obesity is linked to cardiovascular diseases and increasingly common in type 1 diabetes mellitus (T1DM) since the introduction of intensified insulin therapy. Our main aim was to explore associations between obesity and depression, anxiety, alexithymia and self-image measures and to control for lifestyle variables in a sample of persons with T1DM. Secondary aims were to explore associations between abdominal and general obesity and cardiovascular complications in T1DM. Cross sectional study of 284 persons with T1DM (age 18-59 years, men 56%), consecutively recruited from one secondary care hospital diabetes clinic in Sweden. Assessments were performed with self-report instruments (Hospital Anxiety and Depression Scale, Toronto Alexithymia Scale-20 items and Structural Analysis of Social Behavior). Anthropometrics and blood samples were collected for this study and supplemented with data from the patients' medical records. Abdominal obesity was defined as waist circumference men/women (meters): ≥1.02/≥0.88, and general obesity as BMI ≥30 kg/m 2 for both genders. Abdominal obesity was chosen in the analyses due to the high association with cardiovascular complications. Different explanatory logistic regression models were elaborated for the associations and calibrated and validated for goodness of fit with the data variables. The prevalence of abdominal obesity was 49/284 (17%), men/women: 8%/29% ( P  < 0.001). Abdominal obesity was associated with women (AOR 4.9), physical inactivity (AOR 3.1), alexithymia (AOR 2.6) and age (per year) (AOR 1.04). One of the three alexithymia sub factors, "difficulty identifying feelings" (AOR 3.1), was associated with abdominal obesity. Gender analyses showed that abdominal obesity in men was associated with "difficulty identifying feelings" (AOR 7.7), and in women with use of antidepressants (AOR 4.3) and physical inactivity (AOR 3.6). Cardiovascular complications were associated with abdominal obesity (AOR 5

  20. Does abdominal obesity accelerate the effect of hypertriglyceridemia on impaired fasting glucose?

    PubMed

    Lee, Soojin; Chun, Kihong; Lee, Soonyoung; Kim, Daejung

    2010-05-01

    This study sought to determine whether abdominal obesity is a risk factor for impaired fasting glucose (IFG) and hypertriglyceridemia and to verify whether moderate effect of abdominal obesity on the relationship between IFG and hypertriglyceridemia in Korea. Data from the Korean National Health and Nutrition Examination Survey was used for the analysis. The study population included 5,938 subjects aged 20 year old drawn from non-diabetic participants in a health examination survey. The subjects were classified according to the presence of abdominal obesity based on waist circumference, IFG based on their fasting blood glucose level, and hypertriglyceridemia on their fasting triglyceride. The multivariate-adjusted odds ratios for the occurrence of hypertriglyceridemia were 2.91 in the abdominal obesity group as compared with the nonobesity group and 1.31 in subjects with IFG compared with the normoglycemia controls. Abdominal obesity was found to be positively moderated in the interaction between waist circumference and fasting blood sugar. The moderate effect between abdominal obesity and IFG contributes to the development of hypertriglyceridemia in Korea.

  1. Trends in obesity and abdominal obesity in the older adult population of Spain (2000-2010).

    PubMed

    Gutiérrez-Fisac, Juan Luis; León-Muñoz, Luz M; Regidor, Enrique; Banegas, Josér; Rodríguez-Artalejo, Fernando

    2013-01-01

    This work examines the trend in obesity and abdominal obesity in the Spanish population aged 60 years and over during the first decade of the 21st century. We analyze data from a representative study of the Spanish population aged 60 years and older conducted in 2000-2001 and from the Study on Nutrition and Cardiovascular Risk in Spain (ENRICA) conducted in 2008-2010. In men, the distribution of BMI did not vary in the period 2000-2010. In contrast, in women there was a reduction in both mean BMI--from 29.3 to 28.8 kg/m2--and the prevalence of obesity--from 40.8 to 36.3%. This decline was greatest in women aged 60-69 years. In men, no significant changes were observed in mean waist circumference (WC) or in the prevalence of abdominal obesity. In contrast, WC decreased by 3.6 cm and abdominal obesity prevalence by 12.7% in women. The decline was greatest in women aged 60-69 years, in whom mean WC decreased by 5.1 cm and abdominal obesity prevalence by 18.6%. These findings show that the frequency of obesity has begun to decline in Spanish women aged 60 and over. The causes of this decline are unclear.

  2. miRNA Signatures of Insulin Resistance in Obesity.

    PubMed

    Jones, Angela; Danielson, Kirsty M; Benton, Miles C; Ziegler, Olivia; Shah, Ravi; Stubbs, Richard S; Das, Saumya; Macartney-Coxson, Donia

    2017-10-01

    Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity. One hundred seventy-five miRNAs were analyzed in females with obesity (insulin sensitivity, n = 11; insulin resistance, n = 19; type 2 diabetes, n = 15) and without obesity (n = 12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated. One hundred six miRNAs were significantly (adjusted P ≤ 0.05) different between controls and at least one obesity phenotype, including miRNAs with the following attributes: previously reported roles in obesity and altered circulating levels (e.g., miR-122, miR-192); known roles in obesity but no reported changes in circulating levels (e.g., miR-378a); and no current reported role in, or association with, obesity (e.g., miR-28-5p, miR-374b, miR-32). The miRNAs in the latter group were found to be associated with extracellular vesicles. Forty-eight miRNAs showed significant correlations with clinical parameters; stepwise regression retained let-7b, miR-144-5p, miR-34a, and miR-532-5p in a model predictive of insulin resistance (R 2  = 0.57, P = 7.5 × 10 -8 ). Both miR-378a and miR-122 were perturbed in metabolically relevant tissues in a murine model of obesity. This study expands on the role of extracellular miRNAs in insulin-resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity. © 2017 The Obesity Society.

  3. [Project to improve abdominal obesity in day care ward psychiatric patients].

    PubMed

    Liu, Yu-Chieh; Wang, Hui-Yu; Huang, Hui-Ling; Chen, Min-Li

    2011-06-01

    Over half (57.14%) of patients in our ward suffer from abdominal obesity. This rate is on a continuing upward trend. Reasons for such obesity include lack of physical activity classes, inadequate physical activity, high calorie diets and unhealthy eating habits, chronic diseases and drug side effects, poor motivation to reduce weight, and lack of crisis awareness of abdominal obesity. This project was designed to lessen the problem of abdominal obesity among psychiatric day care inpatients. Resolution measures implemented included: (1) arranging aerobic exercise classes; (2) scheduling classes to teach patients healthy diet habits and knowledge regarding diseases and drugs; (3) holding a waistline reduction competition; (4) displaying health education bulletin boards; (5) holding a quiz contest with prizes for correct answers. The eight abdominally obese patients in the ward achieved an average waist circumference reduction of 2.9 cm and the overall abdominal obesity rate in the ward fell to 35.7%. BMI, eating habits, and awareness of weight loss importance and motivation all improved. The outcome achieved targeted project objectives. We recommend the integration of obesity prevention into routine ward activities and quality control indicators. Nurses should provide patients with weight loss concepts, regularly monitor risk factors, and encourage patient family cooperation to maintain medical care quality.

  4. Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance.

    PubMed

    Saad, M J A; Santos, A; Prada, P O

    2016-07-01

    Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities. ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

  5. Exercise rescues obese mothers' insulin sensitivity, placental hypoxia and male offspring insulin sensitivity.

    PubMed

    Fernandez-Twinn, Denise S; Gascoin, Geraldine; Musial, Barbara; Carr, Sarah; Duque-Guimaraes, Daniella; Blackmore, Heather L; Alfaradhi, Maria Z; Loche, Elena; Sferruzzi-Perri, Amanda N; Fowden, Abigail L; Ozanne, Susan E

    2017-03-14

    The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance. Maternal hyperinsulinemia (independent of maternal body weight and composition) strongly associated with offspring insulin resistance. To test causality, we implemented an exercise intervention that improved maternal insulin sensitivity without changing maternal body weight or composition. This maternal intervention prevented excess placental lipid deposition and hypoxia (independent of sex) and insulin resistance in male offspring. We conclude that hyperinsulinemia is a key programming factor and therefore an important interventional target during obese pregnancy, and propose moderate exercise as a promising strategy to improve metabolic outcome in both the obese mother and her offspring.

  6. Educational inequality in the occurrence of abdominal obesity: Pró-Saúde Study

    PubMed Central

    Alves, Ronaldo Fernandes Santos; Faerstein, Eduardo

    2015-01-01

    OBJECTIVE To estimate the degree of educational inequality in the occurrence of abdominal obesity in a population of non-faculty civil servants at university campi. METHODS In this cross-sectional study, we used data from 3,117 subjects of both genders aged 24 to 65-years old, regarding the baseline of Pró-Saúde Study, 1999-2001. Abdominal obesity was defined according to abdominal circumference thresholds of 88 cm for women and 102 cm for men. A multi-dimensional, self-administered questionnaire was used to evaluate education levels and demographic variables. Slope and relative indices of inequality, and Chi-squared test for linear trend were used in the data analysis. All analyses were stratified by genders, and the indices of inequality were standardized by age. RESULTS Abdominal obesity was the most prevalent among women (43.5%; 95%CI 41.2;45.9), as compared to men (24.3%; 95%CI 22.1;26.7), in all educational strata and age ranges. The association between education levels and abdominal obesity was an inverse one among women (p < 0.001); it was not statistically significant among men (p = 0.436). The educational inequality regarding abdominal obesity in the female population, in absolute terms (slope index of inequality), was 24.0% (95%CI 15.5;32.6). In relative terms (relative index of inequality), it was 2.8 (95%CI 1.9;4.1), after the age adjustment. CONCLUSIONS Gender inequality in the prevalence of abdominal obesity increases with older age and lower education. The slope and relative indices of inequality summarize the strictly monotonous trend between education levels and abdominal obesity, and it described educational inequality regarding abdominal obesity among women. Such indices provide relevant quantitative estimates for monitoring abdominal obesity and dealing with health inequalities. PMID:26465669

  7. Obesity, insulin resistance, and type 1 diabetes mellitus.

    PubMed

    Polsky, Sarit; Ellis, Samuel L

    2015-08-01

    To summarize recent studies about obesity, insulin resistance, and type 1 diabetes mellitus (T1DM). Overweight and obesity continue to be prevalent among individuals with T1DM. Obesity rates appear to have reached a plateau among children with T1DM in some parts of the world. The risk for development of T1DM is increased by obesity and may occur at an earlier age among obese individuals with a predisposition. Obesity increases the risk for comorbidities among individuals with T1DM, especially metabolic syndrome, and microvascular and macrovascular diseases. Metformin, glucagon-like peptide-1 agonist therapy, sodium glucose cotransporter-2 inhibitor therapy, and bariatric surgery may be beneficial therapies for glucose control, comorbidity management, and obesity among adults with T1DM. Insulin resistance may be improved among obese individuals with T1DM by biguanides (metformin) and glucagon-like peptide-1 agonists (exenatide). We review the last 18 months of literature on obesity, insulin resistance, and T1DM to highlight new epidemiologic results and treatments.

  8. FREQUENCY OF ABDOMINAL OBESITY AND ITS ASSOCIATION WITH DIABETES MELLITUS AMONG PEOPLE OF PESHAWAR.

    PubMed

    Khan, Attaullah; Faheem, Muhammad; Shah, Syed Tahir; Hadi, Abdul; Rafiullah; Ahmad, Salman; Gul, Adnan Mahmood; Shah, Sayyad Farhat Abbas; Jan, Hikmatullah; Hafizullah, Mohammad

    2015-01-01

    Increased body weight is a major risk factor for the metabolic syndrome which is a cluster of coronary heart disease risk factors, like: hypertension, diabetes mellitus and dyslipidaemia. This study was conducted to determine the frequency of abdominal obesity and diabetes mellitus in the population of Peshawar and association between them. This was a cross sectional study, performed by the Cardiology Department, Lady Reading Hospital Peshawar, in the population of Peshawar. All participants were interviewed in detail regarding known risk factors for coronary artery disease. Waist circumference (≥102 cm in male and ≥88 cm in females) was used as the surrogate marker for abdominal obesity in already diagnosed patients of type-2 diabetes mellitus. A total of 2548 individuals were included, 71.1% were male. Mean age was 37.94±12.59 years. Mean waist circumference was 90.25±13.45cm in males and 90.52±12.52cm in females. Diabetes was present in 4.4% of the participants and abdominal obesity in 56.6% Among the male, abdominal obesity was present in 39.4% and diabetes in 2.9%. Out of 39.4% males with abdominal obesity, 2% were diabetic. Out of 38.6% males with no abdominal obesity, 0.9% was diabetic. Amongst the total 559 (21.1%) female subjects, 17.2% were having abdominal obesity and 1.4% was diabetics. Among 123 (4.8%) females with no abdominal obesity, 0.1% was diabetic. A positive association was established between abdominal obesity and diabetes mellitus with a significant p-valve (<0.05). Abdominal obesity is more common in the local population of Peshawar and associated with type-2 diabetes mellitus.

  9. Prevalence of abdominal obesity among Chinese adults in 2011.

    PubMed

    Du, Pei; Wang, Hui-Jun; Zhang, Bing; Qi, Su-Fen; Mi, Ying-Jun; Liu, Dian-Wu; Tian, Qing-Bao

    2017-06-01

    The prevalence of abdominal obesity is increasing dramatically worldwide. This study aimed to estimate the current prevalence of abdominal obesity from the 2011 China Health and Nutrition Survey (CHNS) and compare the data with other countries. Waist circumference (WC) of 12,326 Chinese adults (aged 20 years or older) from the 2011 CHNS were analyzed by age group and region. Abdominal obesity was defined as a WC ≥90 cm for men and WC ≥80 cm for women based on World Health Organization (WHO) recommendations for Asians. In 2011, the age-adjusted mean WC was 85.9 cm (95% confidence interval [CI], 85.6-86.2 cm) for men and 80.7 cm (95% CI, 80.4-80.9 cm) for women. Based on the WHO recommendations, the age-adjusted prevalence of abdominal obesity was 44.0% (95% CI, 43.1%-44.8%) overall, 35.3% (95% CI, 34.1%-36.6%) in men, and 51.7% (95% CI, 50.5%-52.9%) in women. Moreover, the age-adjusted prevalence was 44.0% (95% CI, 42.7%-45.2%) in rural populations, 42.5% (95% CI, 40.7%-44.2%) in urban populations, and 45.2% (95% CI, 43.5%-46.9%) in megacity populations. The prevalence in China (35.3% for men and 51.7% for women) was lower than in Japan (50.8% for men) and the United States (43.5% for men and 64.7% for women). Similar results were observed when applying the criteria suggested by the Working Group on Obesity in China. In 2011, the age-adjusted prevalence of abdominal obesity in China was 35.3% in men and 51.7% in women. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  10. Insulin sensitivity deteriorates after short-term lifestyle intervention in the insulin sensitive phenotype of obesity.

    PubMed

    Gilardini, Luisa; Vallone, Luciana; Cottafava, Raffaella; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

    2012-01-01

    To investigate the effects of a 3-month lifestyle intervention on insulin sensitivity and its related cardiometabolic factors in obese patients. Anthropometry, body composition, oral glucose tolerance test, lipids, alanine aminotransferase, insulin sensitivity (insulinogenic index (ISI), homeostasis model assessment, β-cell performance (disposition index)) were evaluated in 263 obese women and 93 obese men before and after 3 months of hypocaloric low fat/high protein diet associated with physical activity 30 min/day. Patients were divided into 3 groups according to the intervention-induced ISI changes: group 1 (decrease), group 2 (stability) and group 3 (increase). Insulin sensitivity and the disposition index were significantly higher before the intervention in group 1 than in group 3. BMI, waist circumference, and fat mass significantly decreased in groups 1 and 3 in both sexes. β-cell performance decreased in group 1 and increased in group 3. Metabolic variables improved in group 3, whereas glucose levels increased in women of group 1. The post-intervention insulin sensitivity was lower in group 1 than in group 3. Lifestyle intervention induces changes in insulin sensitivity and metabolic factors that depend on the pre-intervention degree of insulin sensitivity. Weight loss leads to metabolic benefits in insulin-resistant, obese patients, whereas it may paradoxically worsen the metabolic conditions in the insulin-sensitive phenotype of obesity. Copyright © 2012 S. Karger GmbH, Freiburg.

  11. Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity.

    PubMed

    Bhasin, Shalender; Parker, Robert A; Sattler, Fred; Haubrich, Richard; Alston, Beverly; Umbleja, Triin; Shikuma, Cecilia M

    2007-03-01

    had greater increase in lean body mass than placebo (testosterone 1.3%, placebo -0.3, P = 0.02). Plasma insulin, fasting glucose, and total high-density lipoprotein and low-density lipoprotein cholesterol levels did not change significantly. Testosterone therapy was well tolerated. Testosterone therapy in HIV-positive men with abdominal obesity and low testosterone was associated with greater decrease in whole body, total, and sc abdominal fat mass and a greater increase in lean mass compared to placebo. However, changes in visceral fat mass were not significantly different between groups. Further studies are needed to determine testosterone effects on insulin sensitivity and cardiovascular risk.

  12. Effect of tadalafil administration on insulin secretion and insulin sensitivity in obese men.

    PubMed

    González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Hernández-Corona, Diana M; Ramírez-Rodríguez, Alejandra M

    2017-10-01

    To evaluate the effect of tadalafil administration on insulin secretion and insulin sensitivity in obese men without diabetes. A randomized, double-blind, placebo-controlled clinical trial was carried out in obese male patients between 30 and 50 years of age. Eighteen subjects were randomly assigned to two groups of nine patients each. During a 28-day period, subjects received 5 mg orally of tadalafil or placebo each night. Patients were evaluated before and after the intervention. Total insulin secretion and first phase of insulin secretion were calculated by insulinogenic index and Stumvoll index, respectively, and insulin sensitivity was calculated using the Matsuda index. Tolerability and compliance were evaluated permanently throughout the study. There were no significant differences after administration of tadalafil in total insulin secretion (0.82 ± 0.45 vs. 0.61 ± 0.27, p = 0.594), first phase of insulin secretion (1332 ± 487 vs. 1602 ± 800, p = 0.779) and insulin sensitivity (4.6 ± 1.2 vs. 4.9 ± 2.5, p = 0.779). No significant differences were shown in other measurements. Tadalafil administration for 28 days did not modify insulin secretion or insulin sensitivity in obese men.

  13. The prevalence of abdominal obesity is remarkable for underweight and normal weight adolescent girls

    PubMed

    Acar Tek, Nilüfer; Şanlıer, Nevin; Türközü, Duygu

    2017-08-23

    Background/aim: Obesity is a global public health challenge. This study was carried out in order to determine the prevalence of obesity and abdominal obesity in Turkish adolescent girls. Materials and methods: A cross-sectional study was conducted in a total of 1111 adolescent girls aged 12?18 years. The subjects were classified into four groups: underweight, normal, overweight, and obese. Abdominal obesity was defined according to waist circumference (WC) ≥ 90th percentile for Turkish adolescent population references (12-17 years) and waist-to-height ratio (WHtR) ≥ 0.5. Results: The prevalence of underweight was 17.4%, normal weight 68.5%, overweight 12.1%, and obese 2.0%. A total of 16.9% subjects were abdominal obese based on WC and 10.4% based on WHtR. When the four groups were evaluated in terms of abdominal obesity status, prevalence was 6.4% and 2.6% in the underweight, 14.6% and 5.8% in the normal, 60.0% and 37.3% in the overweight, and 88.8% and 77.3% in the obese groups according to WC and WHtR, respectively. Both WC (r: 0.332) and WHtR (r: 0.156) were positively correlated with age (P < 0.05). Conclusion: The prevalence of abdominal obesity was found at high levels for overweight and obese adolescents. It should be emphasized that abdominal obesity is a condition that should be considered for underweight and normal adolescents as well. Therefore, abdominal obesity should be regularly assessed for nonobese adolescents to prevent cardiovascular risks, metabolic syndrome, and other related disease.

  14. Common variants in SOCS7 gene predict obesity, disturbances in lipid metabolism and insulin resistance.

    PubMed

    Tellechea, M L; Steinhardt, A Penas; Rodriguez, G; Taverna, M J; Poskus, E; Frechtel, G

    2013-05-01

    Specific Suppressor of Cytokine Signaling (SOCS) members, such as SOCS7, may play a role in the development of insulin resistance (IR) owing to their ability to inhibit insulin signaling pathways. The objective was to explore the association between common variants and related haplotypes in SOCS7 gene and metabolic traits related to obesity, lipid metabolism and IR. 780 unrelated men were included in a cross-sectional study. We selected three tagged SNPs that capture 100% of SNPs with minor allele frequency ≥ 0.10. Analyses were done separately for each SNP and followed up by haplotype analysis. rs8074124C was associated with both obesity (p = 0.005) and abdominal obesity (p = 0.002) and allele C carriers showed, in comparison with TT carriers, lower BMI (p = 0.001) and waist circumference (p = 0.001). rs8074124CC- carriers showed lower fasting insulin (p = 0.017) and HOMA-IR (p = 0.018) than allele T carriers. rs12051836C was associated with hypertriglyceridemia (p = 0.009) and hypertriglyceridemic waist (p = 0.006). rs12051836CC- carriers showed lower fasting insulin (p = 0.043) and HOMA-IR (p = 0.042). Haplotype-based association analysis (rs8074124 and rs12051836 in that order) showed associations with lipid and obesity -related phenotypes, consistent with single locus analysis. Haplotype analysis also revealed association between haplotype CT and both decreased HDL-C (p = 0.026) and HDL-C (p = 0.014) as a continuous variable. We found, for the first time, significant associations between SOCS7 common variants and related haplotypes and obesity, IR and lipid metabolism disorders. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  15. [Corticotropic axis and chronic stress in abdominal obesity and metabolic syndrome].

    PubMed

    Boullu-Ciocca, S; Verger, P; Bocquier, A; Oliver, C

    2005-12-03

    Several indicators of corticotropic axis hyperactivity have been observed in common abdominal obesity, which is clinically similar to the obesity found in Cushing's syndrome. Corticotropic axis hyperactivity may be involved in the development and metabolic and cardiovascular complications of abdominal obesity. Several mechanisms may be responsible for this hormonal dysregulation: genetic, lifestyle, and nutritional factors, and chronic stress. We note the necessity of methodologically-impeccable clinical studies for an objective evaluation of the role of stress in obesity.

  16. Adolescent Obesity and Insulin Resistance: Roles of Ectopic Fat Accumulation and Adipose Inflammation.

    PubMed

    Caprio, Sonia; Perry, Rachel; Kursawe, Romy

    2017-05-01

    As a consequence of the global rise in the prevalence of adolescent obesity, an unprecedented phenomenon of type 2 diabetes has emerged in pediatrics. At the heart of the development of type 2 diabetes lies a key metabolic derangement: insulin resistance (IR). Despite the widespread occurrence of IR affecting an unmeasurable number of youths worldwide, its pathogenesis remains elusive. IR in obese youth is a complex phenomenon that defies explanation by a single pathway. In this review we first describe recent data on the prevalence, severity, and racial/ethnic differences in pediatric obesity. We follow by elucidating the initiating events associated with the onset of IR, and describe a distinct "endophenotype" in obese adolescents characterized by a thin superficial layer of abdominal subcutaneous adipose tissue, increased visceral adipose tissue, marked IR, dyslipidemia, and fatty liver. Further, we provide evidence for the cellular and molecular mechanisms associated with this peculiar endophenotype and its relations to IR in the obese adolescent. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Mechanisms of insulin resistance in obesity

    PubMed Central

    Ye, Jianping

    2014-01-01

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

  18. HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice

    USDA-ARS?s Scientific Manuscript database

    The effects of hydroxypropyl methylcellulose (HPMC), a highly viscous non-fermentable soluble dietary fiber, were evaluated on adipose tissue inflammation and insulin resistance in diet induced obese (DIO) mice fed a high fat (HF) diet supplemented with either HPMC or insoluble fiber. DIO C57BL/6J m...

  19. The effects of abdominal lipectomy in metabolic syndrome components and insulin sensitivity in females: A systematic review and meta-analysis.

    PubMed

    Seretis, Konstantinos; Goulis, Dimitrios G; Koliakos, Georgios; Demiri, Efterpi

    2015-12-01

    Adipose tissue is an endocrine organ, which is implicated in the pathogenesis of obesity, metabolic syndrome and diabetes. Lipectomy offers a unique opportunity to permanently reduce the absolute number of fat cells, though its functional role remains unclear. This systematic and meta-analysis review aims to assess the effect of abdominal lipectomy on metabolic syndrome components and insulin sensitivity in women. A predetermined protocol, established according to the Cochrane Handbook's recommendations, was used. An electronic search in MEDLINE, Scopus, the Cochrane Library and CENTRAL electronic databases was conducted from inception to May 14, 2015. This search was supplemented by a review of reference lists of potentially eligible studies and a manual search of key journals in the field of plastic surgery. Eligible studies were prospective studies with ≥1month of follow-up that included females only who underwent abdominal lipectomy and reported on parameters of metabolic syndrome and insulin sensitivity. The systematic review included 11 studies with a total of 271 individuals. Conflicting results were revealed, though most studies showed no significant metabolic effects after lipectomy. The meta-analysis included 4 studies with 140 subjects. No significant changes were revealed between lipectomy and control groups. This meta-analysis provides evidence that abdominal lipectomy in females does not affect significantly the components of metabolic syndrome and insulin sensitivity. Further high quality studies are needed to elucidate the potential metabolic effects of abdominal lipectomy. Systematic review registration PROSPERO CRD42015017564 (www.crd.york.ac.uk/PROSPERO). Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats.

    PubMed

    Wang, Zhong Q; Zhang, Xian H; Russell, James C; Hulver, Matthew; Cefalu, William T

    2006-02-01

    Chromium is one of the few trace minerals for which a specific cellular mechanism of action has not been identified. Recent in vitro studies suggest that chromium supplementation may improve insulin sensitivity by enhancing insulin receptor signaling, but this has not been demonstrated in vivo. We investigated the effect of chromium supplementation on insulin receptor signaling in an insulin-resistant rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and based on calculated water intake, rats randomized to CrPic received 80 microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis) biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin stimulation to assess insulin signaling. Obese rats treated with CrPic had significantly improved glucose disposal rates and demonstrated a significant increase in insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle compared with obese controls. The increase in cellular signaling was not associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt. However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower in obese rats administered CrPic than obese controls. When corrected for protein content, PTP1B activity was also significantly lower in obese rats administered CrPic than obese controls. Our data suggest that chromium supplementation of obese, insulin-resistant rats may improve insulin action by enhancing intracellular signaling.

  1. The prevalence of abdominal obesity among pupils with visual impairment in Poland.

    PubMed

    Wrzesińska, Magdalena; Urzędowicz, Beata; Nawarycz, Tadeusz; Motylewski, Sławomir; Pawlicki, Lucjan

    2017-10-01

    Obesity particularly affects young people with disabilities, whose ability to participate in health promotion programs is reduced. The aim of the study is to determine the prevalence of abdominal obesity among students with visual impairment in Poland according to waist-to-height ratio, including indicators such as gender, age or certain additional coexisting disabilities or disorders. A total of 238 students who were blind or partially-sighted, aged 7.35-23.35 years (mean age 15.5; ±3.9 years), were included in the study. Abdominal obesity was estimated using waist-to-height ratio; a cutoff point of ≥0.50 was determined as central obesity. Abdominal obesity was identified among 26.9% [N = 64] of the participants: 33.1% [N = 41] of male students and 20.2% [N = 23] of female students (ch2 = 5.02; p = 0.025; Phi = 0.145). Of all the students, the multivariate logistic regression showed that abdominal obesity was one and a half times more likely to be detected in the 7-9 year age group (OR = 1.56; 95% CI 0.58-4.18; P = 0.376) than the 19-23 year age group. However, among the female subjects, abdominal obesity was over six times more common in the 7-9 year group (OR = 6.48; 95% CI 1.29-32.5; P = 0.022) than in the group of early adults. Central obesity was detected almost three times more frequently among students with visual impairment and additional intellectual disability (OR = 2.99; 95% CI 0.52-17.1; P = 0.215) than those with only visual impairment. Prevention programs aimed at reducing abdominal obesity among pupils with visual impairment from special schools are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The role of dietary fat in obesity-induced insulin resistance.

    PubMed

    Lackey, Denise E; Lazaro, Raul G; Li, Pingping; Johnson, Andrew; Hernandez-Carretero, Angelina; Weber, Natalie; Vorobyova, Ivetta; Tsukomoto, Hidekazu; Osborn, Olivia

    2016-12-01

    Consumption of excess calories results in obesity and insulin resistance and has been intensively studied in mice and humans. The objective of this study was to determine the specific contribution of dietary fat rather than total caloric intake to the development of obesity-associated insulin resistance. We used an intragastric feeding method to overfeed excess calories from a low-fat diet (and an isocalorically matched high-fat diet) through a surgically implanted gastric feeding tube to generate obesity in wild-type mice followed by hyperinsulinemic-euglycemic clamp studies to assess the development of insulin resistance. We show that overfeeding a low-fat diet results in levels of obesity similar to high-fat diet feeding in mice. However, despite a similar body weight, obese high-fat diet-fed mice are more insulin resistant than mice fed an isocaloric low-fat diet. Therefore, increased proportion of calories from dietary fat further potentiates insulin resistance in the obese state. Furthermore, crossover diet studies revealed that reduction in dietary fat composition improves glucose tolerance in obesity. In the context of the current obesity and diabetes epidemic, it is particularly important to fully understand the role of dietary macronutrients in the potentiation and amelioration of disease. Copyright © 2016 the American Physiological Society.

  3. Clinical usefulness of the thickness of preperitoneal and subcutaneous fat layer in the abdomen estimated by ultrasonography for diagnosing abdominal obesity in each type of impaired glucose tolerance in man.

    PubMed

    Soyama, Akiko; Nishikawa, Tetsuo; Ishizuka, Toshiharu; Ito, Hiroko; Saito, Jun; Yagi, Kazuo; Saito, Yasushi

    2005-04-01

    For this study we enrolled 1,615 males who were admitted to our hospital for a general health check-up. Plasma glucose (PG) and insulin were measured during 75 g OGTT, and abdominal obesity was assessed by ultrasonography in all subjects. We divided them into several groups: normal glucose tolerance (NGT), high-normal glucose tolerance (h-NGT) who showed >10.0 nmol/l at 1 hr PG among those with NGT, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and DM, according to the results of 75 g OGTT. The aim of the present study was to clarify the clinical characteristics of pre-diabetic disorders relating to metabolic syndrome by comparing various parameters including body mass index (BMI), blood levels of various lipids and abdominal wall fat index (AFI) calculated from the thickness of preperitoneal (Pmax) and subcutaneous (Smin) fat layer in the abdomen estimated by ultrasonography with insulin sensitivity determined by homeostatic model assessment (HOMA-IR) in each type of abnormal glucose regulation as classified by PG changes in 75 g OGTT. We also investigated the relationship between insulin secretion capability and insulin sensitivity to delineate the characteristics of each type of abnormal glucose regulation, and compared the area under the insulin curve (AUCins) and the time axis, and the ability of early insulin secretion by glucose loading (insulinogenic index: I.I.) in each type of abnormal glucose regulation. There was a significant positive correlation between HOMA-IR and Smin or Pmax, suggesting that Smin and Pmax may reflect insulin sensitivity. Abdominal obesity, which was diagnosed from the data of AFI, was present in the h-NGT and IFG + IGT groups, suggesting that those groups belong to the clinical entity of metabolic syndrome. HOMA-IR was higher in IFG than in IGT, although I.I. was reduced and AUCins was increased in IFG as well as in IGT. h-NGT demonstrated a slightly lower I.I. and higher AUCins, compared with IGT

  4. Association between meal intake behaviour and abdominal obesity in Spanish adults.

    PubMed

    Keller, Kristin; Rodríguez López, Santiago; Carmenate Moreno, Margarita M

    2015-09-01

    The study aims to evaluate the association between abdominal obesity with meal intake behaviour such as having a forenoon meal, having an afternoon meal and snacking. This cross-sectional study includes n = 1314 participants aged 20-79 who were interviewed during the Cardiac health "Semanas del Corazon" events in four Spanish cities (Madrid, Las Palmas, Seville and Valencia) in 2008. Waist circumference, weight and height were assessed to determine abdominal obesity (waist circumference: ≥88 cm in women and ≥102 cm in men) and BMI, respectively. The intake of forenoon and afternoon meal and snacking between the participants' regular meals were assessed with a questionnaire that also included individual risk factors. The information obtained about diet was required to calculate an Unhealthy Habit Score and a score reflecting the Achievement of Dietary Guidelines. Adjusted logistic regressions were used to examine the association between abdominal obesity and the mentioned meal intake behaviour controlling for sex, age, individual risk factors, BMI and diet. Having an afternoon meal (OR 0.60; 95% CI (0.41-0.88)) was negatively associated with abdominal obesity after adjusting for all confounders, whereas the positive association of snacking (OR 1.39; 95% CI (1.05-1.85)) was not independent of BMI (OR 1.25; 95% CI (0.84-1.87)). Taking a forenoon meal did not show any associations (OR 0.92; 95% CI (0.63-1.34)) with abdominal obesity. The results obtained could be helpful in the promotion of healthy habits in nutritional education programmes and also in health programmes preventing abdominal obesity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth

    PubMed Central

    van der Heijden, Gert-Jan; Wang, Zhiyue J.; Chu, Zili; Toffolo, Gianna; Manesso, Erica; Sauer, Pieter J.J.; Sunehag, Agneta L.

    2010-01-01

    Introduction Data are limited on the metabolic effects of resistance exercise (strength training) in adolescents. Purpose The objective of this study was to determine whether a controlled resistance exercise program without dietary intervention or weight loss, reduces body fat accumulation, increases lean body mass, and improves insulin sensitivity and glucose metabolism in sedentary obese Hispanic adolescents. Methods Twelve obese adolescents (15.5±0.5y; 35.3 ±0.8kg/m2;40.8±1.5% body fat), completed a 12 wk resistance exercise program (2×1h/wk, exercising all major muscle groups). At baseline and completion of the program, body composition was measured by DXA, abdominal fat distribution by Magnetic Resonance Imaging, hepatic and intramyocellular fat by Magnetic Resonance Spectroscopy, peripheral insulin sensitivity by the Stable Labeled IV Glucose Tolerance Test and hepatic insulin sensitivity by the Hepatic Insulin Sensitivity Index =1000/(GPR*fasting insulin). Glucose production rate (GPR), gluconeogenesis and glycogenolysis were quantified using Stable Isotope-Gas Chromatography/Mass Spectrometry techniques. Results All participants were normoglycemic. The exercise program resulted in significant strength gain in both upper and lower body muscle groups. Body weight increased from 97.0±3.8 to 99.6±4.2 kg (p<0.01). The major part (~80%) was accounted for by increased lean body mass (55.7±2.8 to 57.9±3.0 kg; p≤0.01).Total, visceral, hepatic and intramyocellular fat content remained unchanged. Hepatic insulin sensitivity increased by 24±9% (p<0.05), while peripheral insulin sensitivity did not change significantly. GPR decreased by 8±1% (p<0.01) due to a 12±5% decrease in glycogenolysis (p<0.05). Conclusion We conclude that a controlled resistance exercise program without weight loss increases strength and lean body mass, improves hepatic insulin sensitivity and decreases GPR without affecting total fat mass or visceral, hepatic and intramyocellular

  6. Prevalence and geographic variation of abdominal obesity in 7- and 9-year-old children in Greece; World Health Organization Childhood Obesity Surveillance Initiative 2010.

    PubMed

    Hassapidou, Maria; Tzotzas, Themistoklis; Makri, Evangelia; Pagkalos, Ioannis; Kaklamanos, Ioannis; Kapantais, Efthymios; Abrahamian, Annet; Polymeris, Antonis; Tziomalos, Konstantinos

    2017-01-28

    In children, abdominal obesity is a better predictor of the presence of cardiovascular risk factors than body mass index (BMI)-defined obesity. We aimed to evaluate the prevalence of abdominal obesity in the Greek pediatric population and to assess the impact of residence on the prevalence of both BMI-defined and abdominal obesity. In the context of the Childhood Obesity Surveillance Initiative of the World Health Organization (WHO) Regional Office for Europe, a national representative sample of 7.0-7.9 and 9.0-9.9-year-old children was evaluated (n = 2,531 and 2,700, respectively). Overweight and obesity according to BMI were estimated using both the WHO and International Obesity Task Force cut-off points. Abdominal obesity was defined as waist circumference/height ratio >0.5. The prevalence of abdominal obesity did not differ between 7-year-old boys and girls (25.2 and 25.3%, respectively; p = NS). Among 9-year-old children, abdominal obesity was more prevalent in boys than in girls (33.2 and 28.2%, respectively; p = 0.005). Among normal weight and overweight children, the prevalence of abdominal obesity was 1.6-6.8 and 21.8-49.1%, respectively. The prevalence of abdominal and BMI-defined obesity did not differ between children living in the mainland, in Crete and in other islands except in 7-year-old girls, where the prevalence of BMI-defined obesity was highest in those living in Crete, intermediate in those living in other islands and lowest in those living in the mainland. In 9-year-old boys and in 7- and 9-year-old girls, the prevalence of abdominal obesity was highest in children living in Athens and lowest in children living in Thessaloniki, whereas children living in other cities and in villages showed intermediate rates. The prevalence of abdominal obesity in 7-year-old boys and the prevalence of BMI-defined obesity did not differ between children living in cities and villages. The prevalence of pediatric abdominal obesity in Greece is among

  7. The role of production of adipsin and leptin in the development of insulin resistance in patients with abdominal obesity.

    PubMed

    Vasilenko, M A; Kirienkova, E V; Skuratovskaia, D A; Zatolokin, P A; Mironyuk, N I; Litvinova, L S

    2017-07-01

    We investigated the tissue-specific features of the production of adipokines (leptin and adipsin) by adipose tissue in obese patients depending on the degree of obesity and the state of carbohydrate metabolism. An increase in the content of adipsin and leptin in the blood plasma was found. In patients with varying degrees of obesity with and without type 2 diabetes mellitus (DM 2), we determined the level of tissue-specific expression of LEP and CFD genes encoding leptin and adipsin, respectively. The contribution of different adipose tissue depots to the blood plasma level of adipsin and leptin in obese patients with and without DM 2 was established. The disturbance of reciprocal relationships between adipsin and leptin in obesity is associated with the development of insulin resistance.

  8. Yogurt consumption and abdominal obesity reversion in the PREDIMED study.

    PubMed

    Santiago, S; Sayón-Orea, C; Babio, N; Ruiz-Canela, M; Martí, A; Corella, D; Estruch, R; Fitó, M; Aros, F; Ros, E; Gómez-García, E; Fiol, M; Lapetra, J; Serra-Majem, Ll; Becerra-Tomás, N; Salas-Salvadó, J; Pinto, X; Schröder, H; Martínez, J A

    2016-06-01

    Evidence on the association yogurt consumption and obesity is not conclusive. The aim of this study was to prospectively evaluate the association between yogurt consumption, reversion of abdominal obesity status and waist circumference change in elderly. 4545 individuals at high cardiovascular risk were prospectively followed. Total, whole-fat and low-fat yogurt consumption were assessed using food frequency questionnaires. Generalized estimating equations were used to analyze the association between yogurt consumption and waist circumference change (measured at baseline and yearly during the follow-up). Logistic regression models were used to evaluate the odds ratios (ORs) and 95% CIs of the reversion rate of abdominal obesity for each quintile of yogurt consumption compared with the lowest quintile. After multivariable adjustment, the average yearly waist circumference change in the quintiles of whole-fat yogurt consumption was: Q1: 0.00, Q2: 0.00 (-0.23 to 0.23), Q3: -0.15 (-0.42 to 0.13), Q4: 0.10 (-0.21 to 0.42), and Q5: -0.23 (-0.46 to -0.00) cm; p for trend = 0.05. The ORs for the reversion of abdominal obesity for whole-fat yogurt consumption were Q1: 1.00, Q2: 1.40 (1.04-1.90), Q3: 1.33 (0.94-1.89), Q4: 1.21 (0.83-1.77), and Q5: 1.43 (1.06-1.93); p for trend = 0.26. Total yogurt consumption was not significantly associated with reversion of abdominal obesity status and a lower waist circumference. However, consumption of whole-fat yogurt was associated with changes in waist circumference and higher probability for reversion of abdominal obesity. Therefore, it seems that whole-fat yogurt has more beneficial effects in management of abdominal obesity in elderly population at high cardiovascular risk. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All

  9. Abdominal obesity, ethnicity and gastro‐oesophageal reflux symptoms

    PubMed Central

    Corley, Douglas A; Kubo, Ai; Zhao, Wei

    2007-01-01

    Objective To evaluate the associations between abdominal obesity and gastro‐oesophageal reflux disease (GORD), and their interactions with ethnicity and gender. Design A cross‐sectional study. Participants completed detailed symptom questionnaires and underwent a standardised examination, including anthropometric measurements. Setting A large integrated healthcare system. Patients 80 110 members of the Kaiser Permanente multiphasic health check‐up cohort. Main outcome measures Gastro‐oesophageal reflux‐type symptoms. Results Recent reflux‐type symptoms were present in 11% of the population. The multivariate OR for symptoms with an abdominal diameter (adjusted for body mass index (BMI)) of ⩾26 vs <16.3 cm was 1.85 (95% CI 1.55 to 2.21) for the white population, 0.95 (95% CI 0.61 to 1.48) for the black population and 0.64 (95% CI 0.18 to 2.30) for Asians. The mean abdominal diameter was greater in men (22.0 cm, 95% CI 21.9 to 22.0) than in women (20.1 cm, 95% CI 20.0 to 20.1, p<0.01), but the risk of symptoms for any given diameter did not differ markedly by gender. The association between increasing BMI and symptoms was also much stronger among the white population than among the black population. The association between BMI and reflux‐type symptoms was partially mediated through abdominal diameter. Conclusions There was a consistent association between abdominal diameter (independent of BMI) and reflux‐type symptoms in the white population, but no consistent associations in the black population or Asians. The BMI association was also strongest among the white population. These findings, combined with the increased prevalence of abdominal obesity in male subjects, suggest that an increased obesity may disproportionately increase GORD‐type symptoms in the white population and in male subjects. PMID:17047097

  10. 45Obesity, Insulin Resistance and Free Fatty Acids

    PubMed Central

    Boden, Guenther

    2011-01-01

    Purpose of Review to describe the role of FFA as a cause for insulin resistance in obese people. Recent Findings elevated plasma FFA levels can account for a large part of insulin resistance in obese patients with type 2 diabetes. Insulin resistance is clinically important because it is closely associated with several diseases including T2DM, hypertension, dyslipidemia and abnormalities in blood coagulation and fibrinolysis. These disorders are all independent risk factors for cardiovascular disease (heart attacks, strokes and peripheral arterial disease). The mechanism by which FFA can cause insulin resistance, although not completely known, include generation of lipid metabolites (diacylglycerol), proinflammatory cytokines (TNF-α, IL1β, IL6, MCP1) and cellular stress including oxidative and endoplasmic reticulum stress. Summary increased plasma FFA levels are an important cause of obesity associated insulin resistance and cardiovascular disease. Therapeutic application of this knowledge is hampered by the lack of readily accessible methods to measure FFA and by the lack of medications to lower plasma FFA levels. PMID:21297467

  11. Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

    PubMed

    Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

    2014-08-05

    The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Aerobic Exercise and Weight Loss Reduce Vascular Markers of Inflammation and Improve Insulin Sensitivity in Obese Women

    PubMed Central

    Ryan, Alice S.; Ge, Shealinna; Blumenthal, Jacob B.; Serra, Monica C.; Prior, Steven J.; Goldberg, Andrew P.

    2014-01-01

    Background/Objectives To examine the relationships of plasma and tissue markers of systemic and vascular inflammation to obesity and insulin resistance and determine the effects of aerobic exercise training+weight loss (AEX+WL) and weight loss (WL) on these biomarkers. Design Prospective controlled study. Participants Seventy-seven overweight and obese sedentary postmenopausal women. Interventions Six months, 3d/wk AEX+WL (n=37) or WL (n=40). Measurements Total body dual-energy x-ray absorptiometry, abdominal computed tomography scans, hyperinsulinemic-euglycemic clamps, adipose tissue biopsies (n=28), and blood for Homeostasis model assessment-insulin resistance, and soluble forms of intracellular adhesion molecule (sICAM-1) and vascular CAM-1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Results Body weight, %fat, visceral fat, triglyceride levels and systolic blood pressure decreased comparably after WL and AEX+WL (P<0.05). VO2max increased 16% after AEX+WL (P<0.001). Insulin resistance decreased in both groups (P<0.01). Glucose utilization increased 10% (P< 0.05) after AEX+WL and 8% with WL (P=0.07). AEX+WL and WL decreased CRP by 29% and 21%, (P<0.05). SAA levels decreased two-fold more after AEX+WL (−19%, P<0.05) than with WL (−9%, P=0.08). Plasma sICAM-1 and sVCAM-1 levels did not change; however, women with the greatest reduction in plasma sICAM-1 levels had the greatest reductions in fasting glucose, insulin and insulin resistance (P<0.05). Gluteal ICAM mRNA levels decreased 27% after AEX+WL (P<0.05) and did not change after WL. Conclusion Obesity and insulin resistance worsen markers of systemic and vascular inflammation. A reduction in plasma sICAM-1 is important to improve insulin sensitivity. CRP and SAA and tissue ICAM decrease with exercise and weight loss, suggesting that exercise training is a necessary component of lifestyle modification in obese postmenopausal women. PMID:24635342

  13. AMP-activated Protein Kinase (AMPK): Does This Master Regulator of Cellular Energy State Distinguish Insulin Sensitive from Insulin Resistant Obesity?

    PubMed Central

    Valentine, Rudy J.; Ruderman, Neil B.

    2014-01-01

    Although a correlation exists between obesity and insulin resistance, roughly 25 % of obese individuals are insulin sensitive. AMP-activated protein kinase (AMPK) is a cellular energy sensor that among its many actions, integrates diverse physiological signals to restore energy balance. In addition, in many situations it also increases insulin sensitivity. In this context, AMPK activity is decreased in very obese individuals undergoing bariatric surgery who are insulin resistant compared to equally obese patients who are insulin sensitive. In this review, we will both explore what distinguishes these individuals, and evaluate the evidence that diminished AMPK is associated with insulin resistance and metabolic syndrome-associated disorders in other circumstances. PMID:24891985

  14. Skeletal muscle inflammation and insulin resistance in obesity.

    PubMed

    Wu, Huaizhu; Ballantyne, Christie M

    2017-01-03

    Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance.

  15. Skeletal muscle inflammation and insulin resistance in obesity

    PubMed Central

    Wu, Huaizhu; Ballantyne, Christie M.

    2017-01-01

    Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance. PMID:28045398

  16. The effect of abdominal resistance training and energy restricted diet on lateral abdominal muscles thickness of overweight and obese women.

    PubMed

    Noormohammadpour, Pardis; Kordi, Ramin; Dehghani, Saeed; Rostami, Mohsen

    2012-07-01

    The role of transabdominal muscles (external oblique, internal oblique and transversus abdominis) on core stability has been shown previously. Energy restricted diet and abdominal resistance training are commonly used by overweight and obese people to reduce their weight. In this study we investigated the impact of 12 weeks concurrent energy restricted diet and abdominal resistance training on the thickness of the lateral abdominal muscles of 19 obese and overweight women employing ultrasonography in resting and drawing-in maneuvers. The results showed significant increase of the muscle thicknesses during drawing-in maneuver after 12 weeks intervention. Based on our findings, it can be concluded that 12 weeks concurrent abdominal resistance training and energy restricted diet in addition to weight loss lead to improvement of transabdominal muscles thickness in obese and overweight people. Considering the role of these muscles in core stability, using this therapeutic protocol in obese people, particularly in those who have weakness of these muscles might be helpful. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral Adipose Tissue of 5α-Dihydrotestosterone-Induced Animal Model of Polycystic Ovary Syndrome.

    PubMed

    Milutinović, Danijela Vojnović; Nikolić, Marina; Veličković, Nataša; Djordjevic, Ana; Bursać, Biljana; Nestorov, Jelena; Teofilović, Ana; Antić, Ivana Božić; Macut, Jelica Bjekić; Zidane, Abdulbaset Shirif; Matić, Gordana; Macut, Djuro

    2017-09-01

    Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Evaluation of beta-cell sensitivity to glucose and first-phase insulin secretion in obese dogs.

    PubMed

    Verkest, Kurt R; Fleeman, Linda M; Rand, Jacquie S; Morton, John M

    2011-03-01

    To compare beta-cell sensitivity to glucose, first-phase insulin secretion, and glucose tolerance between dogs with naturally occurring obesity of > 2 years' duration and lean dogs. 17 client-owned obese or lean dogs. Frequently sampled IV glucose tolerance tests were performed with minimal model analysis on 6 obese dogs and matched controls. Glucagon stimulation tests were performed on 5 obese dogs and matched controls. Obese dogs were half as sensitive to the effects of insulin as lean dogs. Plasma glucose concentrations after food withholding did not differ significantly between groups; plasma insulin concentrations were 3 to 4 times as great in obese as in lean dogs. Obese dogs had plasma insulin concentrations twice those of lean dogs after administration of glucose and 4 times as great after administration of glucagon. First-phase insulin secretion was greater in obese dogs. Obese dogs compensated for obesity-induced insulin resistance by secreting more insulin. First-phase insulin secretion and beta-cell glucose sensitivity were not lost despite years of obesity-induced insulin resistance and compensatory hyperinsulinemia. These findings help explain why dogs, unlike cats and humans, have not been documented to develop type 2 diabetes mellitus.

  19. Prevalence of abdominal obesity and its association with cardio metabolic risk factors among older adults in Ecuador.

    PubMed

    Orces, Carlos H; Montalvan, Martha; Tettamanti, Daniel

    2017-12-01

    To describe the prevalence of abdominal obesity and its association with cardio metabolic risk factors among older adults in Ecuador. The present study used data from the National Survey of Health, Wellbeing, and Aging survey to examine the prevalence of abdominal obesity according to certain demographic, behavioral, and health characteristics of the participants. Logistic regression models adjusted for potential confounders were used to evaluate the association of abdominal obesity with cardio metabolic risk factors. Of 2053 participants aged 60 years and older, the prevalence of abdominal obesity was 65.9% (95% CI; 62.2%, 69.4%) in women and 16.3% (95% CI; 13.8%, 19.2%) in men. Notably, a higher prevalence of abdominal obesity was seen among residents in the urban areas of the country, those who reported their race as black or mulatto, individuals with sedentary lifestyle and obesity, and older adults with greater number of comorbidities. Moreover, after adjustment for potential confounders, women with abdominal obesity were 2.0, 2.8, and 1.6 times more likely to have diabetes, the metabolic syndrome, and hypertriglyceridemia as compared with those without, respectively. Likewise, men with abdominal obesity had 51% and 22% higher rates of hypertension and diabetes than their non-obese counterparts, respectively. the prevalence of abdominal obesity is high among older adults in Ecuador. Moreover, abdominal obesity is significantly associated with cardio metabolic risk factors. Therefore, further research is needed to evaluate sociodemographic and nutritional determinants of this emerging public health burden among older Ecuadorians. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  20. Obesity decreases the oxidant stress induced by tobacco smoke in a rat model.

    PubMed

    Montaño, Martha; Pérez-Ramos, J; Esquivel, A; Rivera-Rosales, R; González-Avila, G; Becerril, C; Checa, M; Ramos, C

    2016-09-01

    Obesity and emphysema are associated with low-grade systemic inflammation and oxidant stress. Assuming that the oxidant stress induced by emphysema would be decreased by obesity, we analyzed the oxidant/antioxidant state in a rat model combining both diseases simultaneously. Obesity was induced using sucrose, while emphysema by exposure to tobacco smoke. End-points evaluated were: body weight, abdominal fat, plasma dyslipidemia and malondialdehyde (MDA), insulin and glucose AUC, activities of Mn-superoxide dismutase (Mn-SOD), glutathione reductase (GR), glutathione transferase (GST) and glutathione peroxidase (GPx); lung MnSOD and 3-nitrotyrosine (3-NT) immunostaining, and expression of αV and β6 integrin subunits. In rats with obesity, the body weight, abdominal fat, plasma triglyceride levels, glucose AUC, insulin levels, GST activity, and αV and β6 integrin expressions were amplified. The rats with emphysema had lower values of body weight, abdominal fat, plasma insulin, triglycerides and glucose AUC but higher values of plasma MDA, GPx activity, and the lung expression of the αV and β6 integrins. The combination of obesity and emphysema compared to either condition alone led to diminished body weight, abdominal fat, plasma insulin MDA levels, GPx and GST activities, and αV and β6 integrin expressions; these parameters were all previously increased by obesity. Immunostaining for MnSOD augmented in all experimental groups, but the staining for 3-NT only increased in rats treated with tobacco alone or combined with sucrose. Results showed that obesity reduces oxidant stress and integrin expression, increasing antioxidant enzyme activities; these changes seem to partly contribute to a protective mechanism of obesity against emphysema development.

  1. Effect of abdominal resistance exercise on abdominal subcutaneous fat of obese women: a randomized controlled trial using ultrasound imaging assessments.

    PubMed

    Kordi, Ramin; Dehghani, Saeed; Noormohammadpour, Pardis; Rostami, Mohsen; Mansournia, Mohammad Ali

    2015-01-01

    The aim of this study was to compare the effect of diet and an abdominal resistance training program to diet alone on abdominal subcutaneous fat thickness and waist circumference of overweight and obese women. This randomized clinical trial included 40 overweight and obese women randomly divided into 2 groups: diet only and diet combined with 12 weeks of abdominal resistance training. Waist and hip circumferences and abdominal skin folds of the subjects were measured at the beginning and 12 weeks after the interventions. In addition, abdominal subcutaneous fat thickness of the subjects was measured using ultrasonography. Percentage body fat and lean body mass of all the subjects were also measured using a bioelectric impedance device. After 12 weeks of intervention, the weight of participants in both groups decreased; but the difference between the 2 groups was not significant (P = .45). Similarly, other variables including abdominal subcutaneous fat, waist circumference, hip circumference, body mass index, body fat percentage, and skin fold thickness were reduced in both groups; but there were no significant differences between the groups. This study found that abdominal resistance training besides diet did not reduce abdominal subcutaneous fat thickness compared to diet alone in overweight or obese women. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  2. Vitamin D insufficiency and insulin resistance in obese adolescents

    PubMed Central

    Tosh, Aneesh K.; Belenchia, Anthony M.

    2014-01-01

    Obese adolescents represent a particularly vulnerable group for vitamin D deficiency which appears to have negative consequences on insulin resistance and glucose homeostasis. Poor vitamin D status is also associated with future risk of type 2 diabetes and metabolic syndrome in the obese. The biological mechanisms by which vitamin D influences glycemic control in obesity are not well understood, but are thought to involve enhancement of peripheral/hepatic uptake of glucose, attenuation of inflammation and/or regulation of insulin synthesis/secretion by pancreatic β cells. Related to the latter, recent data suggest that the active form of vitamin, 1,25-dihydroxyvitamin D, does not impact insulin release in healthy pancreatic islets; instead they require an environmental stressor such as inflammation or vitamin D deficiency to see an effect. To date, a number of observational studies exploring the relationship between the vitamin D status of obese adolescents and markers of glucose homeostasis have been published. Most, although not all, show significant associations between circulating 25-hydroxyvitamn D concentrations and insulin sensitivity/resistance indices. In interpreting the collective findings of these reports, significant considerations surface including the effects of pubertal status, vitamin D status, influence of parathyroid hormone status and the presence of nonalcoholic fatty liver disease. The few published clinical trials using vitamin D supplementation to improve insulin resistance and impaired glucose tolerance in obese adolescents have yielded beneficial effects. However, there is a need for more randomized controlled trials. Future investigations should involve larger sample sizes of obese adolescents with documented vitamin D deficiency, and careful selection of the dose, dosing regimen and achievement of target 25-hydroxyvitamn D serum concentrations. These trials should also include clamp-derived measures of in vivo sensitivity and

  3. Role of intestinal inflammation as an early event in obesity and insulin resistance

    PubMed Central

    Ding, Shengli; Lund, Pauline K.

    2013-01-01

    Purpose of review To highlight recent evidence supporting a concept that intestinal inflammation is a mediator or contributor to development of obesity and insulin resistance. Recent findings Current views suggest that obesity-associated systemic and adipose tissue inflammation promote insulin resistance, which underlies many obesity-linked health risks. Diet-induced changes in gut microbiota also contribute to obesity. Recent findings support a concept that high fat diet and bacteria interact to promote early inflammatory changes in the small intestine that contribute to development of or susceptibility to obesity and insulin resistance. This review summarizes the evidence supporting a role of intestinal inflammation in diet-induced obesity and insulin resistance and discusses mechanisms. Summary The role of diet-induced intestinal inflammation as an early biomarker and mediator of obesity, and insulin resistance warrants further study. PMID:21587067

  4. Whole-Body and Hepatic Insulin Resistance in Obese Children

    PubMed Central

    Ibarra-Reynoso, Lorena del Rocío; Pisarchyk, Liudmila; Pérez-Luque, Elva Leticia; Garay-Sevilla, Ma. Eugenia; Malacara, Juan Manuel

    2014-01-01

    Background Insulin resistance may be assessed as whole body or hepatic. Objective To study factors associated with both types of insulin resistance. Methods Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (<6.67 ng/ml). We determined metabolite and hormone levels and performed a liver ultrasound. Results The majority, 73.1%, of obese children had whole-body insulin resistance and hepatic insulin resistance, while 7% did not have either type. HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother's BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver. Conclusion In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance. PMID:25411786

  5. Aerobic exercise and weight loss reduce vascular markers of inflammation and improve insulin sensitivity in obese women.

    PubMed

    Ryan, Alice S; Ge, Shealinna; Blumenthal, Jacob B; Serra, Monica C; Prior, Steven J; Goldberg, Andrew P

    2014-04-01

    To examine the relationships between plasma and tissue markers of systemic and vascular inflammation and obesity and insulin resistance and determine the effects of aerobic exercise training plus weight loss (AEX+WL) and weight loss (WL) alone on these biomarkers. Prospective controlled study. Veterans Affairs Medical Center and University research setting. Overweight and obese sedentary postmenopausal women (N = 77). Six months, 3 d/wk AEX+WL (n = 37) or WL (n = 40). Total-body dual-energy X-ray absorptiometry, abdominal computed tomography, hyperinsulinemic-euglycemic clamps (a criterion standard method of assessing insulin sensitivity), adipose tissue biopsies (n = 28), and blood for homeostasis model assessment-insulin resistance, and soluble forms of intracellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Body weight (P < .001), percentage of fat (P < .001), visceral fat (P < .005), triglyceride levels (P < .001), and systolic blood pressure decreased comparably after WL and AEX+WL (P = .04). Maximal oxygen consumption increased 16% after AEX+WL (P < .001). Insulin resistance decreased in both groups (P = .005). Glucose utilization according to the clamp increased 10% (P = .04) with AEX+WL and 8% with WL (P = .07). AEX+WL decreased CRP by 29% (P < .001) and WL by 21% (P = .02). SAA levels decreased twice as much after AEX+WL (-19%, P = .02) as after WL (-9%, P = .08). Plasma sICAM-1 and sVCAM-1 levels did not change, but women with the greatest reduction in plasma sICAM-1 levels had the greatest reductions in fasting glucose (P = .02), insulin (P = .02), and insulin resistance (P = .004). Gluteal ICAM messenger ribonucleic acid levels decreased 27% after AEX+WL (P = .02) and did not change after WL. Obesity and insulin resistance worsen markers of systemic and vascular inflammation. A reduction in plasma sICAM-1 is important to improve insulin sensitivity. CRP, SAA, and

  6. Prevalence of overweight/obesity, abdominal obesity and metabolic syndrome and atypical cardiometabolic phenotypes in the adult Romanian population: PREDATORR study.

    PubMed

    Popa, S; Moţa, M; Popa, A; Moţa, E; Serafinceanu, C; Guja, C; Catrinoiu, D; Hâncu, N; Lichiardopol, R; Bala, C; Popa, A; Roman, G; Radulian, G; Timar, R; Mihai, B

    2016-09-01

    The objectives were to assess the prevalence of overweight/obesity, abdominal obesity and metabolic syndrome (MetS), and to evaluate the characteristics of the metabolically unhealthy lean (MUHL) and metabolically healthy overweight/obese (MHO) phenotypes in a Romanian population-based sample from the PREDATORR study. PREDATORR was an epidemiological study with a stratified, cross-sectional, cluster random sampling design. Participants were classified into four cardiometabolic phenotypes based on the BMI, the cut-off value being 25 kg/m(2), and the presence of MetS (defined according to the Harmonization definition 2009): MUHL, MHO, metabolically healthy lean (MHL) and metabolically unhealthy overweight/obese (MUHO). Overall, 2681 subjects aged 20-79 years were included in the analysis. The overall age and sex-adjusted prevalence of obesity was 31.90 %, overweight was 34.7 %, abdominal obesity was 73.90 % and MetS was 38.50 %. The age- and sex-adjusted prevalence of MHO phenotype was 31.60 %, while MUHL phenotype prevalence was 3.90 %. MUHL and MHO participants had a cardiometabolic profile, kidney function and CVD risk intermediary between MHL and MUHO. MUHL had higher odds of being associated with CVD risk (OR 5.8; p < 0.001), abdominal obesity, prediabetes, diabetes, hypertriglyceridemia and hypo-HDL cholesterolemia than MHL, while MHO phenotype was associated with hypo-HDL cholesterolemia (OR 3.1; p = 0.002), prediabetes (OR 2.9; p < 0.001) and abdominal obesity. PREDATORR study showed a high prevalence of obesity/overweight, abdominal obesity and MetS in the adult Romanian population, and their association with kidney function and several cardiometabolic factors.

  7. Sleep Architecture and Glucose and Insulin Homeostasis in Obese Adolescents

    PubMed Central

    Koren, Dorit; Levitt Katz, Lorraine E.; Brar, Preneet C.; Gallagher, Paul R.; Berkowitz, Robert I.; Brooks, Lee J.

    2011-01-01

    OBJECTIVE Sleep deprivation is associated with increased risk of adult type 2 diabetes mellitus (T2DM). It is uncertain whether sleep deprivation and/or altered sleep architecture affects glycemic regulation or insulin sensitivity or secretion. We hypothesized that in obese adolescents, sleep disturbances would associate with altered glucose and insulin homeostasis. RESEARCH DESIGN AND METHODS This cross-sectional observational study of 62 obese adolescents took place at the Clinical and Translational Research Center and Sleep Laboratory in a tertiary care children’s hospital. Subjects underwent oral glucose tolerance test (OGTT), anthropometric measurements, overnight polysomnography, and frequently sampled intravenous glucose tolerance test (FSIGT). Hemoglobin A1c (HbA1c) and serial insulin and glucose levels were obtained, indices of insulin sensitivity and secretion were calculated, and sleep architecture was assessed. Correlation and regression analyses were performed to assess the association of total sleep and sleep stages with measures of insulin and glucose homeostasis, adjusted for confounding variables. RESULTS We found significant U-shaped (quadratic) associations between sleep duration and both HbA1c and serial glucose levels on OGTT and positive associations between slow-wave sleep (N3) duration and insulin secretory measures, independent of degree of obesity, pubertal stage, sex, and obstructive sleep apnea measures. CONCLUSIONS Insufficient and excessive sleep was associated with short-term and long-term hyperglycemia in our obese adolescents. Decreased N3 was associated with decreased insulin secretion. These effects may be related, with reduced insulin secretory capacity leading to hyperglycemia. We speculate that optimizing sleep may stave off the development of T2DM in obese adolescents. PMID:21933909

  8. Differences in Cardiometabolic Risk between Insulin-Sensitive and Insulin-Resistant Overweight and Obese Children.

    PubMed

    Khan, Unab I; McGinn, Aileen P; Isasi, Carmen R; Groisman-Perelstein, Adriana; Diamantis, Pamela M; Ginsberg, Mindy; Wylie-Rosett, Judith

    2015-06-01

    It is known that 15-30% overweight/obese adults do not suffer cardiometabolic consequences. There is limited literature examining factors that can be used to assess cardiometabolic health in overweight/obese children. If such factors can be identified, they would aid in differentiating those most in need for aggressive management. Baseline data from 7- to 12-year-old, overweight, and obese children enrolled in a weight management program at an urban hospital were analyzed. Homeostatic model assessment for insulin resistance (HOMA-IR) <2.6 was used to define insulin-sensitive and HOMA-IR ≥2.6 was used to defined insulin-resistant participants. Demographics, physical activity measures, and cardiometabolic risk factors were compared between the two phenotypes. Odds ratios (ORs) examining the association between intermediate endpoints (metabolic syndrome [MetS], nonalcoholic fatty liver disease [NAFLD], systemic inflammation, and microalbuminuria) and the two metabolic phenotypes were evaluated. Of the 362 overweight/obese participants, 157 (43.5%) were insulin sensitive and 204 (56.5%) were insulin resistant. Compared to the insulin-sensitive group, the insulin-resistant group was older (8.6±1.6 vs. 9.9±1.7; p<0.001) and had a higher BMI z-score (1.89±0.42 vs. 2.04±0.42; p=0.001). After multivariable adjustment, compared to the insulin-sensitive group, the insulin-resistant group had higher odds of having MetS (OR, 5.47; 95% confidence interval [CI]: 1.72, 17.35; p=0.004) and NAFLD (OR, 8.66; 95% CI, 2.48, 30.31; p=0.001), but not systemic inflammation (OR, 1.06; 95% CI: 0.56, 2.03; p=0.86) or microalbuminuria (OR, 1.71; 95% CI, 0.49, 6.04; p=0.403). Using a HOMA-IR value of ≥2.6, clinical providers can identify prepubertal and early pubertal children most at risk. Focusing limited resources on aggressive weight interventions may lead to improvement in cardiometabolic health.

  9. Platelet activity in Chinese obese adolescents with and without insulin resistance.

    PubMed

    Lu, Huimin; Lei, Shundong; Zhao, Jiuming; Chen, Ni

    2014-01-01

    To investigate the platelet activity in Chinese obese adolescents with and without insulin resistance. A cross-sectional study was performed in 159 obese Chinese adolescents to investigate their platelet activity using anthropometrics and biochemical parameters, oral glucose tolerance test and platelet testing. An index of insulin sensitivity, homeostasis model assessment of insulin resistance (HOMA-IR), and plasma fibrinogen, prothrombin fragment 1.2 (PT 1.2), fibrinopeptide A (FPA) and the levels of aggregation to collagen 1 μg/ml, adenosine diphosphate (ADP) 10 μmol/L and arachidonic acid (AA) 0.5 mmol/L were measured. Obese adolescents with insulin resistance had significantly higher HOMA-IR, glucose response curve (AUC), insulin AUC, PT 1.2, FPA and fibrinogen and aggregation (to collagen 1 μg/ml, ADP 10 μmol/L and AA 0.5 mmol/L) comparison with obese adolescents without insulin resistance (P < 0.05). Moreover, a positive correlation was found between both aggregation (to collagen, ADP and AA) and HOMA-IR (ρ = 0.716; P < 0.01, ρ = 0.682; P < 0.01 and ρ = 0.699; P < 0.01, respectively), glucose AUC (ρ = 0.479; P < 0.01, ρ = 0.416; P < 0.01 and ρ = 0.458; P < 0.01, respectively) and insulin AUC (ρ = 0.585; P < 0.01, ρ = 0.511; P < 0.01 and ρ = 0.576; P < 0.01, respectively) in obese adolescents with insulin resistance. Insulin resistance is a major determinant of platelet activation in Chinese obese adolescents.

  10. WNT5A-JNK regulation of vascular insulin resistance in human obesity.

    PubMed

    Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

    2016-12-01

    Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m 2 ) and five metabolically normal non-obese (BMI 26±2 kg/m 2 ) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. © The Author(s) 2016.

  11. WNT5A-JNK regulation of vascular insulin resistance in human obesity

    PubMed Central

    Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

    2017-01-01

    Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m2) and five metabolically normal non-obese (BMI 26±2 kg/m2) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. PMID:27688298

  12. Deletion of Skeletal Muscle SOCS3 Prevents Insulin Resistance in Obesity

    PubMed Central

    Jorgensen, Sebastian Beck; O’Neill, Hayley M.; Sylow, Lykke; Honeyman, Jane; Hewitt, Kimberly A.; Palanivel, Rengasamy; Fullerton, Morgan D.; Öberg, Lisa; Balendran, Anudharan; Galic, Sandra; van der Poel, Chris; Trounce, Ian A.; Lynch, Gordon S.; Schertzer, Jonathan D.; Steinberg, Gregory R.

    2013-01-01

    Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver. Skeletal muscle is an important tissue for controlling energy expenditure and whole-body insulin sensitivity; however, the physiological importance of SOCS3 in this tissue has not been examined. Therefore, we generated mice that had SOCS3 specifically deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance. PMID:22961088

  13. RISK FACTORS FOR ABDOMINAL OBESITY IN CHILDREN AND ADOLESCENTS FROM CRACOW, POLAND (1983-2000).

    PubMed

    Suder, Agnieszka; Chrzanowska, Maria

    2015-03-01

    The aim of this study was to determine abdominal obesity risk factors in two successive cohorts of children and adolescents aged 4-18 from Cracow, Poland, examined during the years of political transformation. The influence of biological, socio-demographic and lifestyle factors on abdominal obesity was analysed by calculating odds ratios and 95% confidence intervals using logistic regression analysis. It was found that for girls obesity in both parents (OR=4.31; 95% CI 1.73-20.70) and high birth weight (OR=1.78; 95% CI 1.12-2.82) were significant risk factors for abdominal obesity in the 1983 cohort. In the 2000 cohort obesity in both parents for boys and girls (boys: OR=5.85; 95% CI 1.36-25.10; girls: OR=4.82; 95% CI 1.17-19.77), low level of parental education in girls (OR=2.06; 95% CI 1.15-3.69), having only one son (OR=1.96; 95% CI 1.36-3.40), parents' smoking habits in girls (OR=2.94; 95% CI 1.46-5.91) and lack of undertaking physical activity in sport clubs in boys (OR=6.11; 95% CI 1.46-25.47) were significant abdominal obesity risk factors. Higher number of hours of leisure time physical activity (OR=0.89; 95% CI 0.81-0.97) significantly lowered the risk of abdominal obesity in boys in the 2000 cohort. The greater differentiation of abdominal obesity risk factors in the 2000 cohort in comparison to the 1983 cohort may have resulted from the social and economic changes taking place in Poland at the end of the 20th century.

  14. Associations of polymorphisms in circadian genes with abdominal obesity in Chinese adult population.

    PubMed

    Ye, Ding; Cai, Shaofang; Jiang, Xiyi; Ding, Ye; Chen, Kun; Fan, Chunhong; Jin, Mingjuan

    2016-09-01

    Circadian rhythm, which is controlled by circadian genes, regulates metabolic balance including the circulating levels of glucose, fatty acids, triglycerides, various hormones and so on. The study aimed to investigate the impact of potential polymorphisms in circadian genes on abdominal obesity among Chinese Han adults. A total of 260 cases with abdominal obesity and 260 controls were recruited by individual matching. Demographic characteristics and lifestyle information were collected by a validated questionnaire, and anthropometric parameters was measured by physical examination. Twenty-three single nucleotide polymorphisms (SNPs) in three circadian genes, CLOCK, CRY1 and CRY2, were genotyped by MassArray technique. Five SNPs significantly deviated from Hardy-Weinberg equilibrium (HWE) among controls, so eighteen SNPs were taken into logistic regression analysis. Independently, CLOCK rs10002541 (CC genotype vs. TT genotype: OR: 0.45, 95% CI: 0.23-0.86), CLOCK rs6850524 (CC genotype vs. GG genotype: OR: 0.50, 95% CI: 0.25-0.99) and CRY1 rs10861688 (TT genotype vs. CC genotype: OR: 0.50, 95% CI: 0.25-0.97) were negatively associated with the risk of abdominal obesity. Haplotype analysis showed that the haplotypes of CG and TG for CLOCK rs10002541 and rs4864546 had significant associations with abdominal obesity. Compared with the carriers of TA, those of CG were observed to have a lower risk (OR: 0.74, 95% CI: 0.56-0.99) of abdominal obesity, and those of TG presented a higher risk (OR: 1.70, 95% CI: 1.03-2.81). Our findings suggest that CLOCK and CRY1 polymorphisms might be involved in individual susceptibility to abdominal obesity in Chinese Han population. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  15. Muramyl Dipeptide-Based Postbiotics Mitigate Obesity-Induced Insulin Resistance via IRF4.

    PubMed

    Cavallari, Joseph F; Fullerton, Morgan D; Duggan, Brittany M; Foley, Kevin P; Denou, Emmanuel; Smith, Brennan K; Desjardins, Eric M; Henriksbo, Brandyn D; Kim, Kalvin J; Tuinema, Brian R; Stearns, Jennifer C; Prescott, David; Rosenstiel, Philip; Coombes, Brian K; Steinberg, Gregory R; Schertzer, Jonathan D

    2017-05-02

    Intestinal dysbiosis contributes to obesity and insulin resistance, but intervening with antibiotics, prebiotics, or probiotics can be limited by specificity or sustained changes in microbial composition. Postbiotics include bacterial components such as lipopolysaccharides, which have been shown to promote insulin resistance during metabolic endotoxemia. We found that bacterial cell wall-derived muramyl dipeptide (MDP) is an insulin-sensitizing postbiotic that requires NOD2. Injecting MDP lowered adipose inflammation and reduced glucose intolerance in obese mice without causing weight loss or altering the composition of the microbiome. MDP reduced hepatic insulin resistance during obesity and low-level endotoxemia. NOD1-activating muropeptides worsened glucose tolerance. IRF4 distinguished opposing glycemic responses to different types of peptidoglycan and was required for MDP/NOD2-induced insulin sensitization and lower metabolic tissue inflammation during obesity and endotoxemia. IRF4 was dispensable for exacerbated glucose intolerance via NOD1. Mifamurtide, an MDP-based drug with orphan drug status, was an insulin sensitizer at clinically relevant doses in obese mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. REGULATION OF OBESITY AND INSULIN RESISTANCE BY NITRIC OXIDE

    PubMed Central

    Sansbury, Brian E.; Hill, Bradford G.

    2014-01-01

    Obesity is a risk factor for developing type 2 diabetes and cardiovascular disease and has quickly become a world-wide pandemic with few tangible and safe treatment options. While it is generally accepted that the primary cause of obesity is energy imbalance, i.e., the calories consumed are greater than are utilized, understanding how caloric balance is regulated has proven a challenge. Many “distal” causes of obesity, such as the structural environment, occupation, and social influences, are exceedingly difficult to change or manipulate. Hence, molecular processes and pathways more proximal to the origins of obesity—those that directly regulate energy metabolism or caloric intake—appear to be more feasible targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin resistant patients, and increasing NO output has remarkable effects on obesity and insulin resistance. This review discusses the role of NO in regulating adiposity and insulin sensitivity and places its modes of action into context with the known causes and consequences of metabolic disease. PMID:24878261

  17. Insulin resistance and endocrine-metabolic abnormalities in polycystic ovarian syndrome: Comparison between obese and non-obese PCOS patients.

    PubMed

    Layegh, Parvin; Mousavi, Zohreh; Farrokh Tehrani, Donya; Parizadeh, Seyed Mohammad Reza; Khajedaluee, Mohammad

    2016-04-01

    Insulin resistance has an important role in pathophysiology of polycystic ovarian syndrome (PCOS). Yet there are certain controversies regarding the presence of insulin resistance in non-obese patients. The aim was to compare the insulin resistance and various endocrine and metabolic abnormalities in obese and non-obese PCOS women. In this cross-sectional study which was performed from 2007-2010, 115 PCOS patients, aged 16-45 years were enrolled. Seventy patients were obese (BMI ≥25) and 45 patients were non-obese (BMI <25). Presence of insulin resistance and endocrine-metabolic abnormalities were compared between two groups. Collected data were analyzed with SPSS version 16.0 and p<0.05 was considered as statistically significant. There was no significant difference in presence of insulin resistance (HOMA-IR >2.3) between two groups (p=0.357). Waist circumference (p<0.001), waist/hip ratio (p<0.001), systolic (p<0.001) and diastolic (p<0.001) blood pressures, fasting blood sugar (p=0.003) and insulin (p=0.011), HOMA-IR (p=0.004), total cholesterol (p=0.001) and triglyceride (p<0.001) were all significantly higher in obese PCOS patients. There was no significant difference in total testosterone (p=0.634) and androstenedione (p=0.736) between groups whereas Dehydroepiandrotendione sulfate (DHEAS) was significantly higher in non-obese PCOS women (p=0.018). There was no case of fatty liver and metabolic syndrome in non-obese patients, whereas they were seen in 31.3% and 39.4% of obese PCOS women, respectively. Our study showed that metabolic abnormalities are more prevalent in obese PCOS women, but adrenal axis activity that is reflected in higher levels of DHEAS was more commonly pronounced in our non-obese PCOS patients.

  18. The high burden of obesity and abdominal obesity in urban Indian schoolchildren: a multicentric study of 38,296 children.

    PubMed

    Misra, Anoop; Shah, Priyali; Goel, Kashish; Hazra, Daya Kishore; Gupta, Rajeev; Seth, Payal; Tallikoti, Pooja; Mohan, Indu; Bhargava, Rooma; Bajaj, Sarita; Madan, Jagmeet; Gulati, Seema; Bhardwaj, Swati; Sharma, Rekha; Gupta, Nidhi; Pandey, Ravindra Mohan

    2011-01-01

    The objective of this study was to assess the prevalence of overweight, obesity and abdominal obesity and their associated factors in a large sample of urban Indian schoolchildren. This is a cross-sectional study conducted in 5 cities in India. Height and weight were measured in 38,296 children and waist circumference was measured in 29,244 children aged 8-18 years. The prevalence was compared with respect to age, gender, type of school and city of residence. The mean ± standard deviation for age was 13.3 ± 2.4 years and 18.3 ± 4.3 kg/m(2) for BMI. The prevalence of overweight and obesity in 8- to 18-year-old children, respectively, was 14.4 and 2.8% by IOTF cutoffs, 14.5 and 4.8% by CDC cutoffs and 18.5 and 5.3% by WHO cutoffs. When applying the cutoffs specific for Indian ethnicity in 14- to 18-year-old children, the prevalence was higher (21.1 and 12.3%, respectively) as compared to the IOTF, WHO and CDC cutoffs. The overall prevalence of abdominal obesity in urban Indian schoolchildren was 4.5%. The prevalence of overweight and abdominal obesity was significantly higher in females than males (p < 0.001). High socioeconomic status and residing in cities with a population greater than 4 million were independently associated with overweight and abdominal obesity (p < 0.001). On extrapolating these data, more than 15 million children would currently be overweight and 4 million abdominally obese in urban India. There is a substantial burden of childhood obesity in India, which necessitates comprehensive urban-based campaigns for its prevention and control. Copyright © 2011 S. Karger AG, Basel.

  19. Intermittent hypoxia increases insulin resistance in genetically obese mice.

    PubMed

    Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

    2003-10-01

    Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J-Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 +/- 11 mg dl-1 on day 0 to 138 +/- 10 mg dl-1 on day 5, P < 0.01), improvement in glucose tolerance without a change in serum insulin levels and an increase in serum leptin levels in comparison with control (2.6 +/- 0.3 vs. 1.7 +/- 0.2 ng ml-1, P < 0.05). Microarray mRNA analysis of adipose tissue revealed that leptin was the only upregulated gene affecting glucose uptake. In obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 +/- 136 % (P < 0.01) increase in serum insulin levels. This increase in insulin secretion after 5 days of intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 +/- 1.1 ng ml-1 at baseline to 9.8 +/- 1.8 ng ml-1 at week 12, P < 0.001) and worsening glucose tolerance, consistent with an increase in insulin resistance. We conclude that the increase in insulin resistance in response to intermittent hypoxia is dependent on the disruption of leptin pathways.

  20. Intermittent Hypoxia Increases Insulin Resistance in Genetically Obese Mice

    PubMed Central

    Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

    2003-01-01

    Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J−Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 ± 11 mg dl−1 on day 0 to 138 ± 10 mg dl−1 on day 5, P < 0.01), improvement in glucose tolerance without a change in serum insulin levels and an increase in serum leptin levels in comparison with control (2.6 ± 0.3 vs. 1.7 ± 0.2 ng ml−1, P < 0.05). Microarray mRNA analysis of adipose tissue revealed that leptin was the only upregulated gene affecting glucose uptake. In obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 ± 136 % (P < 0.01) increase in serum insulin levels. This increase in insulin secretion after 5 days of intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 ± 1.1 ng ml−1 at baseline to 9.8 ± 1.8 ng ml−1 at week 12, P < 0.001) and worsening glucose tolerance, consistent with an increase in insulin resistance. We conclude that the increase in insulin resistance in response to intermittent hypoxia is dependent on the disruption of leptin pathways. PMID:12878760

  1. Abdominal Obesity Indicators: Waist Circumference or Waist-to-hip Ratio in Malaysian Adults Population.

    PubMed

    Ahmad, Norfazilah; Adam, Samia Ibrahim Mohamed; Nawi, Azmawati Mohammed; Hassan, Mohd Rohaizat; Ghazi, Hasanain Faisal

    2016-01-01

    Waist circumference (WC) is an accurate and simple measure of abdominal obesity as compared to waist-hip ratio (WHR). The aim of this study was to determine the correlation between body mass index (BMI) with WC and WHR and suggest cutoff points for WC among Rural Malaysian adults. A cross-sectional study was conducted among 669 respondents from three villages in Tanjung Karang, located in the district of Kuala Selangor. Data collection was carried out by guided questionnaires and anthropometric measures. The prevalence of abdominal obesity for BMI was almost similar for both gender across Caucasian and Asian BMI cutoff points. Based on Caucasian cutoff points, the prevalence of abdominal obesity for WC was 23.8% (male) and 66.4% (female) while for WHR was 6.2% (male) and 54.2% (female). Asian cutoff points gave higher prevalence of abdominal obesity compared to that of WC among male respondents and WHR for both genders. WC showed strong and positive correlation with BMI compared to WHR (in male WC r = 0.78, WHR r = 0.24 and in female WC r = 0.72, WHR r = 0.19; P < 0.001). Receiver operating characteristic curve analysis suggested WC cutoff points of 92.5 cm in men and 85.5 cm in women is the optimal number for detection of abdominal obesity. WC is the best indicator as compared with WHR for abdominal obesity for Malaysian adults.

  2. Adipose extracellular matrix remodelling in obesity and insulin resistance☆

    PubMed Central

    Lin, De; Chun, Tae-Hwa; Kang, Li

    2016-01-01

    The extracellular matrix (ECM) of adipose tissues undergoes constant remodelling to allow adipocytes and their precursor cells to change cell shape and function in adaptation to nutritional cues. Abnormal accumulation of ECM components and their modifiers in adipose tissues has been recently demonstrated to cause obesity-associated insulin resistance, a hallmark of type 2 diabetes. Integrins and other ECM receptors (e.g. CD44) that are expressed in adipose tissues have been shown to regulate insulin sensitivity. It is well understood that a hypoxic response is observed in adipose tissue expansion during obesity progression and that hypoxic response accelerates fibrosis and inflammation in white adipose tissues. The expansion of adipose tissues should require angiogenesis; however, the excess deposition of ECM limits the angiogenic response of white adipose tissues in obesity. While recent studies have focused on the metabolic consequences and the mechanisms of adipose tissue expansion and remodelling, little attention has been paid to the role played by the interaction between peri-adipocyte ECM and their cognate cell surface receptors. This review will address what is currently known about the roles played by adipose ECM, their modifiers, and ECM receptors in obesity and insulin resistance. Understanding how excess ECM deposition in the adipose tissue deteriorates insulin sensitivity would provide us hints to develop a new therapeutic strategy for the treatment of insulin resistance and type 2 diabetes. PMID:27179976

  3. Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: a randomized, controlled trial1234

    PubMed Central

    Nicklas, Barbara J; Wang, Xuewen; You, Tongjian; Lyles, Mary F; Demons, Jamehl; Easter, Linda; Berry, Michael J; Lenchik, Leon; Carr, J Jeffrey

    2009-01-01

    Background: Exercise intensity may affect the selective loss of abdominal adipose tissue. Objective: This study showed whether aerobic exercise intensity affects the loss of abdominal fat and improvement in cardiovascular disease risk factors under conditions of equal energy deficit in women with abdominal obesity. Design: This was a randomized trial in 112 overweight and obese [body mass index (in kg/m2): 25–40; waist circumference >88 cm], postmenopausal women assigned to one of three 20-wk interventions of equal energy deficit: calorie restriction (CR only), CR plus moderate-intensity aerobic exercise (CR + moderate-intensity), or CR plus vigorous-intensity exercise (CR + vigorous-intensity). The diet was a controlled program of underfeeding during which meals were provided at individual calorie levels (≈400 kcal/d). Exercise (3 d/wk) involved treadmill walking at an intensity of 45–50% (moderate-intensity) or 70–75% (vigorous-intensity) of heart rate reserve. The primary outcome was abdominal visceral fat volume. Results: Average weight loss for the 95 women who completed the study was 12.1 kg (±4.5 kg) and was not significantly different across groups. Maximal oxygen uptake (O2max) increased more in the CR + vigorous-intensity group than in either of the other groups (P < 0.05). The CR-only group lost relatively more lean mass than did either exercise group (P < 0.05). All groups showed similar decreases in abdominal visceral fat (≈25%; P < 0.001 for all). However, changes in visceral fat were inversely related to increases in O2max (P < 0.01). Changes in lipids, fasting glucose or insulin, and 2-h glucose and insulin areas during the oral-glucose-tolerance test were similar across treatment groups. Conclusion: With a similar amount of total weight loss, lean mass is preserved, but there is not a preferential loss of abdominal fat when either moderate- or vigorous-intensity aerobic exercise is performed during caloric restriction. This trial was

  4. Altered insulin response to an acute bout of exercise in pediatric obesity.

    PubMed

    Tran, Brian D; Leu, Szu-Yun; Oliver, Stacy; Graf, Scott; Vigil, Diana; Galassetti, Pietro

    2014-11-01

    Pediatric obesity typically induces insulin resistance, often later evolving into type 2 diabetes. While exercise, enhancing insulin sensitivity, is broadly used to prevent this transition, it is unknown whether alterations in the exercise insulin response pattern occur in obese children. Therefore, we measured exercise insulin responses in 57 healthy weight (NW), 20 overweight (OW), and 56 obese (Ob) children. Blood samples were drawn before and after 30 min of intermittent (2 min on, 1 min off) cycling at ~80% VO2max. In a smaller group (14 NW, 6 OW, 15 Ob), a high-fat meal was ingested 45 min preexercise. Baseline glycemia was similar and increased slightly and similarly in all groups during exercise. Basal insulin (pmol/L) was significantly higher in Ob vs. other groups; postexercise, insulin increased in NW (+7± 3) and OW (+5 ± 8), but decreased in Ob (-15±5, p < .0167 vs. NW). This insulin drop in Ob was disproportionately more pronounced in the half of Ob children with higher basal insulin (Ob-H). In all groups, high-fat feeding caused a rapid rise in insulin, promptly corrected by exercise. In Ob, however, insulin rose again 30 min postexercise. Our data indicates a distinct pattern of exercise-induced insulin modulation in pediatric obesity, possibly modulated by basal insulin concentrations.

  5. Familial juvenile autoimmune hypothyroidism, pituitary enlargement, obesity, and insulin resistance.

    PubMed

    Reutrakul, Sirimon; Hathout, Eba H; Janner, Donald; Hara, Manami; Donfack, Joseph; Bass, Joseph; Refetoff, Samuel

    2004-04-01

    The proband, a 9-year-old Hispanic female, presented with hair loss, strabismus, and weight gain. On magnetic resonance imaging (MRI) she was found to have severe primary hypothyroidism and a large pituitary mass. In addition, acanthosis nigricans, obesity, and hyperinsulinism were observed. Findings were similar in three of four siblings. Thyroid peroxidase antibodies were detected in the father and three of four siblings. Although all family members were obese, and hyperinsulinemia with high proinsulin and C-peptide was found in all except one sibling, only the mother and one child had overt type 2 diabetes mellitus. Because of the unusual association of autoimmune thyroid disease, insulin resistance and obesity rather than insulin deficiency, we searched for possible genetic abnormalities. The HLA haplotypes did not cosegregate with autoimmune thyroid disease or insulin resistance. Mutational analysis of known obesity genes was done. Leptin was not deficient, and sequencing of the proband's DNA showed no mutations in the perixisome proliferator activated receptor (PPAR)-gamma, PPAR-gamma(2), PPAR-alpha or melanocortin 4 receptor genes. Maternally inherited diabetes and deafness was ruled out since no mutations were found in mitochondria DNA. Insulin receptor antibodies were not detected. In conclusion, the remarkably high incidence of childhood autoimmune hypothyroidism, pituitary enlargement, insulin resistance and obesity in this family is not linked to known HLA types or known gene defects.

  6. Excess fat in the abdomen but not general obesity is associated with poorer metabolic and cardiovascular health in premenopausal and postmenopausal Asian women.

    PubMed

    Goh, Victor Hng Hang; Hart, William George

    2018-01-01

    To examine the associations of various metabolites and hormones and hormone replacement therapy (HRT) with obesity. This is a cross-sectional study of 1326 Singaporean women. A DXA-derived percent body fat (PBF) of ≥35% and percent abdominal fat (PAbdF) of >21.8% were used, respectively, to define women with general (GOb) and abdominal (AbdOb) obesity. Higher levels of insulin and glucose, lower levels of HDL, higher levels of TC/HDL and HOMA values, and different levels of some hormones were noted only in the women with abdominal, and not general obesity. The incidence of general and abdominal obesity was higher in postmenopausal women with or without HRT, except that those who were on conjugated estradiol-only HRT had no increase in the incidence of general obesity compared with premenopausal women. Abdominal obesity is associated with insulin resistance and with higher risks of metabolic syndrome and cardiovascular diseases, whereas general obesity is not. Abdominal obesity may predispose to a higher risk of diabetes. The onset of the menopause tends to increase the incidence of general and abdominal obesity, except that postmenopausal women on conjugated estradiol HRT appear to be relatively protected from general obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Childhood obesity and insulin resistance: how should it be managed?

    PubMed

    Ho, Mandy; Garnett, Sarah P; Baur, Louise A

    2014-12-01

    Concomitant with the rise in global pediatric obesity in the past decades, there has been a significant increase in the number of children and adolescents with clinical signs of insulin resistance. Given insulin resistance is the important link between obesity and the associated metabolic abnormalities and cardiovascular risk, clinicians should be aware of high risk groups and treatment options. As there is no universally accepted biochemical definition of insulin resistance in children and adolescents, identification and diagnosis of insulin resistance usually relies on clinical features such as acanthosis nigricans, polycystic ovary syndrome, hypertension, dyslipidemia, and nonalcoholic fatty liver disease. Treatment for reducing insulin resistance and other obesity-associated comorbidities should focus on changes in health behaviors to achieve effective weight management. Lifestyle interventions incorporating dietary change, increased physical activity, and decreased sedentary behaviors, with the involvement of family and adoption of a developmentally appropriate approach, should be used as the first line treatment. Current evidence suggests that the primary objective of dietary interventions should be to reduce total energy intake and a combination of aerobic and resistance training should be encouraged. Metformin can be used in conjunction with a lifestyle intervention program in obese adolescents with clinical insulin resistance to achieve weight loss and to improve insulin sensitivity. Ongoing evaluation and research are required to explore optimal protocol and long-term effectiveness of lifestyle interventions, as well as to determine whether the improvements in insulin sensitivity induced by lifestyle interventions and weight loss will lead to a clinical benefit including reduced cardiovascular morbidity and mortality.

  8. Comparison of two physical activity questionnaires in obese subjects: the NUGENOB study.

    PubMed

    Tehard, Bertrand; Saris, Wim H M; Astrup, Arne; Martinez, J Alfredo; Taylor, Moira A; Barbe, Pierre; Richterova, Blanka; Guy-Grand, Bernard; Sørensen, Thorkild I A; Oppert, Jean-Michel

    2005-09-01

    Simple instruments are needed to assess habitual physical activity (PA) in obese subjects. In a multicenter European obesity project, we tested whether PA assessments by two questionnaires were correlated and similarly associated to selected obesity-related variables. A total of 757 obese subjects (75% female; age 37.1 [7.9] yr, BMI 35.5 [4.9] kg.m(-2), mean [SD]) completed the Baecke questionnaire (assessing work, sport, and nonsport leisure activity) and the short last 7-d version of the International Physical Activity Questionnaire (IPAQ; assessing vigorous, moderate-intensity, walking activity, and sitting). We assessed percent body fat (bioimpedance), waist circumference, and fasting plasma concentrations of glucose, insulin, leptin, and FFA. Insulin sensitivity was assessed by the HOMA index for insulin resistance (HOMAIR). Using the IPAQ, only about one third of men and women were classified as insufficiently active. Total habitual PA assessments by the Baecke and IPAQ were significantly related (Spearman rho = 0.51 in total sample, P < or = 0.0001, with adjustment for age, gender, and center). Using principal component analysis, we built two uncorrelated indices corresponding to general obesity (determined by high body fat and leptin) and abdominal obesity (determined by high waist circumference and HOMAIR). PA scores from both questionnaires were negatively related to general and abdominal obesity indices, except for abdominal obesity with the IPAQ in men. Total PA assessments by the two questionnaires were found to correlate significantly, and the general pattern of associations of PA with general obesity was similar for the two questionnaires. However, the IPAQ may capture less of the relationships between PA and abdominal obesity than the Baecke, especially in men. Reporting of habitual PA in obese subjects with the IPAQ warrants further evaluation against objective assessment methods.

  9. Insulin-sensitive obese children display a favorable metabolic profile.

    PubMed

    Vukovic, Rade; Mitrovic, Katarina; Milenkovic, Tatjana; Todorovic, Sladjana; Soldatovic, Ivan; Sipetic-Grujicic, Sandra; Zdravkovic, Dragan

    2013-02-01

    Most of what is known about the metabolically healthy obese phenomenon is derived from studies in the adult population and no standardized criteria to identify these individuals exist to date. The aim of this study was to determine if the preserved insulin sensitivity evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) index is associated with favorable metabolic profile in the obese children. We studied a group of 248 children and adolescents (150 female, 98 male), aged 5.9-18.9 years with diet-induced obesity (BMI >95th percentile). The entire cohort was divided into quartiles based on levels of insulin resistance determined by HOMA-IR index. Subjects in the lower quartile of HOMA-IR were classified as insulin-sensitive group (ISG), whereas children in the upper quartile were categorized as insulin-resistant group (IRG). The ISG subjects had values of HOMA-IR ≤2.75 while the children from the IRG group had HOMA-IR ≥6.16. Subjects from ISG group had lower basal β-cell activity and were less likely to have impaired fasting glucose or impaired glucose tolerance. Concentrations of LDL and total cholesterol, triglycerides, and transaminases were lower and HDL cholesterol levels were higher in ISG subjects. Findings obtained by the use of Matsuda index correlated well with the findings obtained by the use of HOMA-IR. Lower HOMA-IR values were significantly associated with favorable metabolic profile in studied children, which correlates with findings in the adult population and emphasizes the need for further, longitudinal studies of insulin resistance development in childhood obesity.

  10. Levels of eicosapentaenoic acid in obese schoolchildren with and without insulin resistance.

    PubMed

    Sánchez Meza, Karmina; Tene Pérez, Carlos Enrique; Sánchez Ramírez, Carmen Alicia; Muñiz Valencia, Roberto; Del Toro Equihua, Mario

    2014-09-12

    Obesity in children is now an increasing health risk worldwide in which the insulin-resistance can be present. Studies have linked a diet rich in n-3 fatty acids with a lower prevalence of insulin-resistance. To compare the levels of eicosapentaenoic acid among obese children with and without insulin-resistance. In 56 randomly school-age children with obesity, insulin-resistance was determined by the homeostasis model assessment for insulin-resistance index and the serum levels of eicosapentaenoic acid were determined by gas chromatography. Insulin-resistance was established when the index was >6.0, non- insulin- resistance when that index was within the range of 1.4-5.9. The serum levels of eicosapentaenoic acid were compared with the Kruskal-Wallis and Mann-Whitney U tests, as needed. No differences in age or sex were identified among the groups studied. The anthropometric parameters were significantly higher in the group of children with insulin-resistance than in the other two groups. The children with insulin- resistance had significantly lower levels of eicosapentaenoic acid than the non- insulin-resistance group [12.4% area under the curve vs. 37.4%, p = 0.031], respectively. Obese primary school-aged children with insulin-resistance had lower plasma levels of eicosapentaenoic acid. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  11. Dietary Aloe Improves Insulin Sensitivity via the Suppression of Obesity-induced Inflammation in Obese Mice.

    PubMed

    Shin, Eunju; Shim, Kyu-Suk; Kong, Hyunseok; Lee, Sungwon; Shin, Seulmee; Kwon, Jeunghak; Jo, Tae Hyung; Park, Young-In; Lee, Chong-Kil; Kim, Kyungjae

    2011-02-01

    Insulin resistance is an integral feature of metabolic syndromes, including obesity, hyperglycemia, and hyperlipidemia. In this study, we evaluated whether the aloe component could reduce obesity-induced inflammation and the occurrence of metabolic disorders such as blood glucose and insulin resistance. Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Aloe QDM lowered fasting blood glucose and plasma insulin compared with HFD. Obesity-induced inflammatory cytokine (IL-1β, -6, -12, TNF-α) and chemokine (CX3CL1, CCL5) mRNA and protein were decreased markedly, as was macrophage infiltration and hepatic triglycerides by Aloe QDM. At the same time, Aloe QDM decreased the mRNA and protein of PPARγ/LXRα and 11β-HSD1 both in the liver and WAT. Dietary aloe formula reduces obesity-induced glucose tolerance not only by suppressing inflammatory responses but also by inducing anti-inflammatory cytokines in the WAT and liver, both of which are important peripheral tissues affecting insulin resistance. The effect of Aloe QDM complex in the WAT and liver are related to its dual action on PPARγ and 11β-HSD1 expression and its use as a nutritional intervention against T2D and obesity-related inflammation is suggested.

  12. Insulin Resistance, Metabolic Syndrome, and Polycystic Ovary Syndrome in Obese Youth.

    PubMed

    Platt, Adrienne M

    2015-07-01

    School nurses are well aware of the childhood obesity epidemic in the United States, as one in three youth are overweight or obese. Co-morbidities found in overweight or obese adults were not commonly found in youth three decades ago but are now increasingly "normal" as the obesity epidemic continues to evolve. This article is the second of six related articles discussing the co-morbidities of childhood obesity and discusses the complex association between obesity and insulin resistance, metabolic syndrome, and polycystic ovary syndrome. Insulin resistance increases up to 50% during puberty, which may help to explain why youth are more likely to develop co-morbidities as teens. Treatment of these disorders is focused on changing lifestyle habits, as a child cannot change his or her pubertal progression, ethnicity, or family history. School nurses and other personnel can assist youth with insulin resistance, metabolic syndrome, and polycystic ovary syndrome by supporting their efforts to make changes, reinforcing that insulin resistance is not necessarily type 2 diabetes even if the child is taking medication, and intervening with negative peer pressure. © 2015 The Author(s).

  13. [Studies of diet management and insulin resistance in obese pregnant women].

    PubMed

    Takeda, S; Saitoh, M; Kinoshita, K; Sakamoto, S

    1992-02-01

    In an attempt to determine the principles of diet management in obese pregnant women, the association between maternal weight gain during pregnancy (Group I; weight reduction, Group II; +0-4 kg, Group III; +5-9 kg, Group IV; +10 kg-) and the incidence of the complications was investigated in 151 obese pregnant women. Studies on glucose tolerance and insulin binding to erythrocytes were also undertaken. 1) In Group I, the incidences of C/S, forceps delivery, prolonged labor and complication of PIH were lower than those of other groups. There were no heavy-for-dates and light-for-dates babies in Group I, differing from the other three groups. 2) Plasma levels of glucose and insulin were high in obese pregnant women on 75 g OGTT in the second trimester. The binding sites of insulin to erythrocytes were significantly decreased in obese pregnant women. In conclusion, the risks of pregnancy complicated by obesity were high. Insulin resistance was a characteristic of obese pregnant women. The results of this study suggested that the nutritional requirements for very obese pregnant women should be restricted to maintaining the same weight or losing weight during the course of pregnancy to minimize maternal and perinatal risks.

  14. A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors

    PubMed Central

    Westley, Rosalyne L.; May, Felicity E. B.

    2013-01-01

    Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented. PMID:23983688

  15. Circulating endocannabinoids in insulin sensitive vs. insulin resistant obese postmenopausal women. A MONET group study.

    PubMed

    Abdulnour, Joseph; Yasari, Siham; Rabasa-Lhoret, Rémi; Faraj, May; Petrosino, Stefania; Piscitelli, Fabiana; Prud' Homme, Denis; Di Marzo, Vincenzo

    2014-01-01

    To measure the circulating levels of endocannabinoids and related molecules at fasting, after acute hyperinsulinemia and after weight loss in insulin sensitive vs. insulin resistant obese postmenopausal women. The sample consisted of 30 obese postmenopausal women (age: 58.9 ± 5.2 yrs; BMI: 32.9 ± 3.6 kg/m(2) ). Subjects underwent a 3-hour hyperinsulinaemic-euglycaemic clamp (HEC) (glucose disposal rate (M-value): 10.7 ± 3.3 mg min(-1) kg(-1) FFM) and 6-month weight loss intervention. Participants were classified as insulin sensitive obese (ISO) or insulin resistant obese (IRO) based on a predefined cutoff. Plasma levels of the endocannabinoids, anandamide (AEA), 2-arachidonoylglycerol (2-AG), and of the AEA-related compounds, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), were measured by liquid chromatography-mass spectrometry. IRO presented higher levels of 2-AG (P < 0.05) independently of the HEC and weight loss, whereas the HEC had an independent inhibitory effect on AEA, PEA, and OEA levels (P < 0.05) in both groups. Furthermore, there was an independent stimulatory effect of weight loss only on PEA levels in both groups (P < 0.05). This study is the first to show that higher circulating levels of the endocannabinoid 2-AG are found in IRO compared to ISO postmenopausal women, and that weight loss is associated with an increase in PEA, a PPAR-α ligand. © 2013 The Obesity Society.

  16. Liver fat contents, abdominal adiposity and insulin resistance in non-diabetic prevalent hemodialysis patients.

    PubMed

    Chen, Hung-Yuan; Lin, Chien-Chu; Chiu, Yen-Ling; Hsu, Shih-Ping; Pai, Mei-Fen; Yang, Ju-Yeh; Wu, Hon-Yen; Peng, Yu-Sen

    2014-01-01

    The liver fat contents and abdominal adiposity correlate well with insulin resistance (IR) in the general population. However, the relationship between liver fat content, abdominal adiposity and IR in non-diabetic hemodialysis (HD) patients remains unclear. This study aimed to clarify the associations among these factors. This is a cross-sectional, observational study. All patients received abdominal ultrasound for liver fat content. Abdominal adiposity was quantified with the conicity index (Ci) and waist circumference (WC). We checked the homeostasis model assessment for insulin resistance index (HOMA-IR) for IR. A total of 112 patients (60 women) were analyzed. Subjects with higher liver fat contents and WC had higher IR indices. But Ci did not correlate with IR indices. In both the multi-variable linear regression model and the logistic regression model, only higher liver fat content predicted a severe IR status. Liver fat contents have a remarkable correlation with IR; however, abdominal adiposity, measured either by Ci or WC, dose not independently correlate with IR in non-diabetic prevalent HD patients. © 2014 S. Karger AG, Basel.

  17. Pro-inflammatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with obesity in Egyptian non-diabetic obese children and adolescents.

    PubMed

    Habib, Salem A; Saad, Entsar A; Elsharkawy, Ashraf A; Attia, Zeinab R

    2015-09-01

    To investigate the inter-relationships between adipocytokines, oxidative stress, insulin, Zn and Cu and obesity among Egyptian obese non-diabetic children and adolescents. 72 obese children and adolescents of both sexes (5-17 years) were recruited for the study. 40 healthy normal non-obese persons of matched ages and sexes were used as control group. Lipid profile, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and leptin levels were measured. Malondialdehyde (MDA) and reduced glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were estimated. Micronutrients (Zn and Cu) concentrations in addition to insulin and fasting blood sugar (FBS) levels were also evaluated. Estimation of insulin resistance (homeostatic model assessment (HOMA-IR)) was derived from FBS measurements. Significant elevations (P<0.001) in TNF-α, IL-6, leptin, MDA, Cu and FBS levels and significant decreases (P<0.001) in GSH, Zn levels and SOD activity were detected among obese individuals as compared with control group. Insulin and triglyceride levels were significantly increased in obese male children and HDL-cholesterol level was increased significantly in obese adolescent females compared to controls. However, total cholesterol and LDL-cholesterol levels were significantly high in all obese cases as compared with controls. Insulin resistance was detected in 100% of the patients. We concluded that obesity with pro-inflammatory adipocytokines and hypozincemia together by many mechanisms participate in excessive oxidative stress and are highly associated with inflammation and the development of obesity-related complications. Obesity represents a critical risk factor for development of insulin resistance status. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Lean mass in obese adult subjects correlates with higher levels of vitamin D, insulin sensitivity and lower inflammation.

    PubMed

    Fornari, R; Francomano, D; Greco, E A; Marocco, C; Lubrano, C; Wannenes, F; Papa, V; Bimonte, V M; Donini, L M; Lenzi, A; Aversa, A; Migliaccio, S

    2015-03-01

    Several chronic metabolic alterations are present in obese subjects. While it is well known about the detrimental effect of abdominal adipose tissue on chronic metabolic clinical condition, less is known on the role of lean mass in obese subjects. Thus, the aim of our study was to evaluate the potential correlation of muscle mass, metabolic condition and inflammation status in obese individuals. The study included 426 obese subjects (86 men and 340 female; mean age 44.8 ± 14 years; BMI: 34.9 ± 6.1 kg/m(2)). Exclusion criteria were chronic medical conditions or use of medications affecting bone metabolism, alterations of hormonal and nutritional status, vitamin D supplementation, recent weight loss and prior bariatric surgery. Patients underwent measurements of bone mineral density (lumbar and hip) and body composition (lean mass, total and trunk fat mass) by dual X-ray absorptiometry and were evaluated for hormonal and metabolic profile and inflammatory markers. Higher lean body mass (LM%) was inversely correlated with homeostasis model assessment of insulin resistance (p < 0.0091; r(2) 0.03938) and associated with lower fibrinogen levels (p < 0.0001; r(2) 0.1263). Interestingly, in obese subjects, LM% was associated with higher levels of vitamin D (p < 0.0001, r(2) 0.1140), osteocalcin (p < 0.0001, r(2) 0.2401) and insulin-like growth factor-1 (IGF-1) (p < 0.0002, r(2) 0.1367). Our results show for the first time that in obese patients, higher amounts of lean mass are directly linked to a lower inflammatory profile and to better insulin sensitivity, but also to the presence of higher level of vitamin D and IGF-1. Moreover, these data suggest that higher levels of lean mass in obese people correlate with a better metabolic profile and, thus, strongly suggest the need to develop programs to facilitate an increase in physical activity in obese people.

  19. PCOS is associated with increased CD11c expression and crown-like structures in adipose tissue and increased central abdominal fat depots independent of obesity.

    PubMed

    Huang, Zhi Hua; Manickam, Buvana; Ryvkin, Victoria; Zhou, Xiaohong Joe; Fantuzzi, Giamila; Mazzone, Theodore; Sam, Susan

    2013-01-01

    Adipose tissue macrophage (ATM) infiltration is a major pathway for obesity-induced insulin resistance but has not been studied as a mechanism for insulin resistance in PCOS. We tested whether polycystic ovary syndrome (PCOS) is associated with increased ATM infiltration, especially of inflammatory subtype identified by the CD11c marker. We conducted a case-control study at an academic medical center in the United States. Fourteen PCOS and 14 control women of similar age and body mass index (BMI) underwent a gluteal fat biopsy. Markers of ATM, integrins, TNF-α, and adiponectin, were analyzed by quantitative RT-PCR using a standard curve method. Crown-like structures (CLS) were identified by immunohistochemistry. Abdominal magnetic resonance imaging and frequently sampled i.v. glucose tolerance test were performed to assess abdominal fat and insulin sensitivity (SI). Women with PCOS were compared with control women of similar age and BMI for ATM markers, CLS density, adipose tissue expression of inflammatory cytokines and adiponectin, SI, and abdominal fat depots. Women with PCOS had an increase in CD11c expression (P = 0.03), CLS density (P = 0.001), α5 expression (P = 0.009), borderline increase in TNF-α expression (P = 0.08), and a decrease in adiponectin expression (P = 0.02) in gluteal adipose tissue. Visceral (P = 0.009) and sc abdominal fat (P = 0.005) were increased in PCOS. SI was lower in PCOS (P = 0.008). PCOS is associated with an increase in CD11c expression and CLS density and a decrease in adiponectin expression in sc adipose tissue. Additionally, PCOS is associated with higher central abdominal fat depots independent of BMI. These alterations are present among mostly nonobese women and could represent mechanisms for insulin resistance.

  20. Dietary Aloe Improves Insulin Sensitivity via the Suppression of Obesity-induced Inflammation in Obese Mice

    PubMed Central

    Shin, Eunju; Shim, Kyu-Suk; Kong, Hyunseok; Lee, Sungwon; Shin, Seulmee; Kwon, Jeunghak; Jo, Tae Hyung; Park, Young-In; Lee, Chong-Kil

    2011-01-01

    Background Insulin resistance is an integral feature of metabolic syndromes, including obesity, hyperglycemia, and hyperlipidemia. In this study, we evaluated whether the aloe component could reduce obesity-induced inflammation and the occurrence of metabolic disorders such as blood glucose and insulin resistance. Methods Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results Aloe QDM lowered fasting blood glucose and plasma insulin compared with HFD. Obesity-induced inflammatory cytokine (IL-1β, -6, -12, TNF-α) and chemokine (CX3CL1, CCL5) mRNA and protein were decreased markedly, as was macrophage infiltration and hepatic triglycerides by Aloe QDM. At the same time, Aloe QDM decreased the mRNA and protein of PPARγ/LXRα and 11β-HSD1 both in the liver and WAT. Conclusion Dietary aloe formula reduces obesity-induced glucose tolerance not only by suppressing inflammatory responses but also by inducing anti-inflammatory cytokines in the WAT and liver, both of which are important peripheral tissues affecting insulin resistance. The effect of Aloe QDM complex in the WAT and liver are related to its dual action on PPARγ and 11β-HSD1 expression and its use as a nutritional intervention against T2D and obesity-related inflammation is suggested. PMID:21494375

  1. Prevalence of abdominal obesity in Abia State, Nigeria: results of a population-based house-to-house survey.

    PubMed

    Chukwuonye, Innocent Ijezie; Chuku, Abali; Onyeonoro, Ugochukwu Uchenna; Okpechi, Ikechi Gareth; Madukwe, Okechukwu Ojoemelam; Umeizudike, Theophilus Ifeanyichukwu; Ogah, Okechukwu Samuel

    2013-01-01

    Abdominal obesity is associated with the risk of developing disorders, such as diabetes and hypertension. The objective of this study was to investigate the prevalence of abdominal obesity in Abia State, Nigeria. We carried out a cross-sectional study aimed at ascertaining the prevalence of abdominal obesity in Abia State, Nigeria. Participants in the study were recruited from communities in the three senatorial zones in the state. Screening for abdominal obesity was carried out in these subjects using waist circumference (the National Cholesterol Education Program Third Adult Treatment Panel criteria were used). The World Health Organization Stepwise Approach to Surveillance of chronic disease risk factors was used. Body mass index, anthropometric measurements, and other relevant data were also collected. Data on waist circumference were obtained from 2,807 subjects. The prevalence of obesity using body mass index in the population was 11.12%. In men and women, it was 7.73%, and 14.37%, respectively. The prevalence of abdominal obesity in the population was 21.75%. In men and women, it was 3.2% and 39.2%, respectively. The prevalence of abdominal obesity is high in Nigeria, and needs to be monitored because it is associated with increased cardiovascular risk.

  2. Prevalence of abdominal obesity in Abia State, Nigeria: results of a population-based house-to-house survey

    PubMed Central

    Ijezie, Innocent Chukwuonye; Chuku, Abali; Onyeonoro, Ugochukwu Uchenna; Okpechi, Ikechi Gareth; Madukwe, Okechukwu Ojoemelam; Umeizudike, Theophilus Ifeanyichukwu; Ogah, Okechukwu Samuel

    2013-01-01

    Background and objective Abdominal obesity is associated with the risk of developing disorders, such as diabetes and hypertension. The objective of this study was to investigate the prevalence of abdominal obesity in Abia State, Nigeria. Materials and methods We carried out a cross-sectional study aimed at ascertaining the prevalence of abdominal obesity in Abia State, Nigeria. Participants in the study were recruited from communities in the three senatorial zones in the state. Screening for abdominal obesity was carried out in these subjects using waist circumference (the National Cholesterol Education Program Third Adult Treatment Panel criteria were used). The World Health Organization Stepwise Approach to Surveillance of chronic disease risk factors was used. Body mass index, anthropometric measurements, and other relevant data were also collected. Results Data on waist circumference were obtained from 2,807 subjects. The prevalence of obesity using body mass index in the population was 11.12%. In men and women, it was 7.73%, and 14.37%, respectively. The prevalence of abdominal obesity in the population was 21.75%. In men and women, it was 3.2% and 39.2%, respectively. Conclusion The prevalence of abdominal obesity is high in Nigeria, and needs to be monitored because it is associated with increased cardiovascular risk. PMID:23946664

  3. Management of obesity in non- insulin- dependent diabetes mellitus.

    PubMed

    Cheah, J S

    1998-12-01

    Obesity is common in non-insulin-dependent diabetes mellitus (NIDDM) patients; in Singapore in a cohort of 314 diabetics, 44.3% were overweight. Management of obesity in diabetics differs from that in non-diabetics in that it is more urgent; weight maintenance is more difficult and hypoglycaemic medication may cause weight changes. However, like in the non-diabetic, management of obesity in the diabetic requires a pragmatic and realistic approach. A team approach is required: the help of a nurse educator, a dietitian, behaviour modification therapist, exercise therapist and others are required. A detailed history, careful physical examination and relevant investigations are required to assess the severity of the diabetic state and to exclude an occasional underlying cause of the obesity in the obese NIDDM patient. Weight loss is urgent in the obese NIDDM patient, especially for those with android obesity. There must be a reduction in energy intake. Weight loss leads to an improvement in glucose tolerance and in insulin sensitivity, as well as to a reduction in lipid levels and to a fall in blood pressure in the hypertensive. Exercise is of limited short-term value measured in terms of weight reduction, except in the younger obese NIDDM patient; but it does allow improvement in overall metabolic control and, long-term, is critical for preferred weight maintenance. The biguanide, Metformin, is the hypoglycaemic drug of choice as it leads to consistent weight reduction. The sulphonylureas may cause weight gain. Insulin should be avoided where possible as it causes further weight gain. Other hypoglycaemic agents include Glucobay (alpha-glucosidase inhibitor) and Troglitazone (insulin sensitizer) which do not alter the weight. Orlistat (lipase inhibitor) is promising as it causes reduction of weight, blood glucose and lipid levels. Anti-obesity drugs (noradrenergic and serotonergic agents) have modest effects on weight reduction in the obese NIDDM patient; a widely

  4. Insulin growth factor-1 correlates with higher bone mineral density and lower inflammation status in obese adult subjects.

    PubMed

    Fornari, Rachele; Marocco, Chiara; Francomano, Davide; Fittipaldi, Simona; Lubrano, Carla; Bimonte, Viviana M; Donini, Lorenzo M; Nicolai, Emanuele; Aversa, Antonio; Lenzi, Andrea; Greco, Emanuela A; Migliaccio, Silvia

    2018-06-01

    Obesity is a severe public health problem worldwide, leading to an insulin-resistant state in liver, adipose, and muscle tissue, representing a risk factor for type 2 diabetes mellitus, cardiovascular diseases, and cancer. We have shown that abdominal obesity is associated with homeostasis derangement, linked to several hormonal and paracrine factors. Data regarding potential link between GH/IGF1 axis, bone mineral density, and inflammation in obesity are lacking. Thus, aim of this study was to evaluate correlation among IGF-1, BMD, and inflammation in obese individuals. The study included 426 obese subjects, mean age 44.8 ± 14 years; BMI 34.9 ± 6.1. Exclusion criteria were chronic medical conditions, use of medications affecting bone metabolism, hormonal and nutritional status, recent weight loss, and prior bariatric surgery. Patients underwent measurements of BMD and body composition by DEXA and were evaluated for hormonal, metabolic profile, and inflammatory markers. In this population, IGF-1 was inversely correlated with abdominal FM% (p < 0.001, r 2  = 0.12) and directly correlated with osteocalcin (OSCA) (p < 0.002, r 2  = 0.14). A negative correlation was demonstrated between IGF-1 levels and nonspecific inflammatory index, such as fibrinogen (p < 0.01, r 2  = 0.04) and erythrocyte sedimentation rate (p < 0.0001, r 2  = 0.03). IGF-1 was directly correlated with higher BMD, at both lumbar (p < 0.02, r 2  = 0.03) and femoral site (p < 0.04, r 2  = 0.03). In conclusion, our results show that higher levels of serum IGF-1 in obese patients correlate with lower inflammatory pattern and better skeletal health, as demonstrated by higher BMD and osteocalcin levels. These results lead to speculate the existence of a bone-adipose-muscle interplay modulating energy homeostasis, glucose, bone metabolism, and chronic inflammation in individuals affected by abdominal obesity.

  5. Sitting Time and Obesity or Abdominal Obesity in Older South Koreans: Korean National Health and Nutrition Examination Survey 2013.

    PubMed

    Sohn, Minsung; Cho, Kyung-Hwan; Han, Kyung-Do; Choi, Mankyu; Kim, Yang-Hyun

    2017-01-01

    We examined relationships between sitting time and obesity or abdominal obesity according to sex and socioeconomic status in elderly people. We analyzed data from the Korean National Health and Nutrition Examination Survey 2013, and 1565 participants were included in the study. Multivariate logistic regression analysis was used to examine relationships between sitting time and obesity or abdominal obesity according to sex and socioeconomic status. Sitting time was positively correlated with body mass index in men and women and waist circumference in men. When considering socioeconomic factors, men who sat for 5 hours or longer and fell within the lowest income were more likely to have obesity and abdominal obesity relative to men who sat for 5 hours or shorter and earned higher incomes (odds ratio [95% confidence interval] = 1.80 [1.14-2.84] and 1.63 [1.02-2.61] respectively), and women who sat for 5 hours or longer and fell within the lowest educational level were more likely to have obesity relative to women who sat for 5 hours or less and were educated to a higher level (1.24 [1.01-1.85]). Strategies to reduce sedentary behavior would help to prevent obesity in older men who earn low incomes and women with lower levels of educational attainment.

  6. Association of General and Abdominal Obesity With Hypertension, Dyslipidemia and Prediabetes in the PREDAPS Study.

    PubMed

    Sangrós, F Javier; Torrecilla, Jesús; Giráldez-García, Carolina; Carrillo, Lourdes; Mancera, José; Mur, Teresa; Franch, Josep; Díez, Javier; Goday, Albert; Serrano, Rosario; García-Soidán, F Javier; Cuatrecasas, Gabriel; Igual, Dimas; Moreno, Ana; Millaruelo, J Manuel; Carramiñana, Francisco; Ruiz, Manuel Antonio; Pérez, Francisco Carlos; Iriarte, Yon; Lorenzo, Ángela; González, María; Álvarez, Beatriz; Barutell, Lourdes; Mayayo, M Soledad; Del Castillo, Mercedes; Navarro, Emma; Malo, Fernando; Cambra, Ainhoa; López, Riánsares; Gutiérrez, M Ángel; Gutiérrez, Luisa; Boente, Carmen; Mediavilla, J Javier; Prieto, Luis; Mendo, Luis; Mansilla, M José; Ortega, Francisco Javier; Borras, Antonia; Sánchez, L Gabriel; Obaya, J Carlos; Alonso, Margarita; García, Francisco; Gutiérrez, Ángela Trinidad; Hernández, Ana M; Suárez, Dulce; Álvarez, J Carlos; Sáenz, Isabel; Martínez, F Javier; Casorrán, Ana; Ripoll, Jazmín; Salanova, Alejandro; Marín, M Teresa; Gutiérrez, Félix; Innerárity, Jaime; Álvarez, M Del Mar; Artola, Sara; Bedoya, M Jesús; Poveda, Santiago; Álvarez, Fernando; Brito, M Jesús; Iglesias, Rosario; Paniagua, Francisca; Nogales, Pedro; Gómez, Ángel; Rubio, José Félix; Durán, M Carmen; Sagredo, Julio; Gijón, M Teresa; Rollán, M Ángeles; Pérez, Pedro P; Gamarra, Javier; Carbonell, Francisco; García-Giralda, Luis; Antón, J Joaquín; de la Flor, Manuel; Martínez, Rosario; Pardo, José Luis; Ruiz, Antonio; Plana, Raquel; Macía, Ramón; Villaró, Mercè; Babace, Carmen; Torres, José Luis; Blanco, Concepción; Jurado, Ángeles; Martín, José Luis; Navarro, Jorge; Sanz, Gloria; Colas, Rafael; Cordero, Blanca; de Castro, Cristina; Ibáñez, Mercedes; Monzón, Alicia; Porta, Nuria; Gómez, María Del Carmen; Llanes, Rafael; Rodríguez, J José; Granero, Esteban; Sánchez, Manuel; Martínez, Juan; Ezkurra, Patxi; Ávila, Luis; de la Sen, Carlos; Rodríguez, Antonio; Buil, Pilar; Gabriel, Paula; Roura, Pilar; Tarragó, Eduard; Mundet, Xavier; Bosch, Remei; González, J Carles; Bobé, M Isabel; Mata, Manel; Ruiz, Irene; López, Flora; Birules, Marti; Armengol, Oriol; de Miguel, Rosa Mar; Romera, Laura; Benito, Belén; Piulats, Neus; Bilbeny, Beatriz; Cabré, J José; Cos, Xavier; Pujol, Ramón; Seguí, Mateu; Losada, Carmen; de Santiago, A María; Muñoz, Pedro; Regidor, Enrique

    2018-03-01

    Some anthropometric measurements show a greater capacity than others to identify the presence of cardiovascular risk factors. This study estimated the magnitude of the association of different anthropometric indicators of obesity with hypertension, dyslipidemia, and prediabetes (altered fasting plasma glucose and/or glycosylated hemoglobin). Cross-sectional analysis of information collected from 2022 participants in the PREDAPS study (baseline phase). General obesity was defined as body mass index ≥ 30kg/m 2 and abdominal obesity was defined with 2 criteria: a) waist circumference (WC) ≥ 102cm in men/WC ≥ 88cm in women, and b) waist-height ratio (WHtR) ≥ 0.55. The magnitude of the association was estimated by logistic regression. Hypertension showed the strongest association with general obesity in women (OR, 3.01; 95%CI, 2.24-4.04) and with abdominal obesity based on the WHtR criterion in men (OR, 3.65; 95%CI, 2.66-5.01). Hypertriglyceridemia and low levels of high-density lipoprotein cholesterol showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.49; 95%CI, 1.68-3.67 and OR, 2.70; 95%CI, 1.89-3.86) and with general obesity in men (OR, 2.06; 95%CI, 1.56-2.73 and OR, 1.68; 95%CI, 1.21-2.33). Prediabetes showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.48; 95%CI, 1.85-3.33) and with abdominal obesity based on the WC criterion in men (OR, 2.33; 95%CI, 1.75-3.08). Abdominal obesity indicators showed the strongest association with the presence of prediabetes. The association of anthropometric indicators with hypertension and dyslipidemia showed heterogeneous results. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Recent Advances in Obesity-Induced Inflammation and Insulin Resistance

    PubMed Central

    Tateya, Sanshiro; Kim, Francis; Tamori, Yoshikazu

    2013-01-01

    It has been demonstrated in rodents and humans that chronic inflammation characterized by macrophage infiltration occurs mainly in adipose tissue or liver during obesity, in which activation of immune cells is closely associated with insulin sensitivity. Macrophages can be classified as classically activated (M1) macrophages that support microbicidal activity or alternatively activated (M2) macrophages that support allergic and antiparasitic responses. In the context of insulin action, M2 macrophages sustain insulin sensitivity by secreting IL-4 and IL-10, while M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines, such as TNFα. Polarization of M1/M2 is controlled by various dynamic functions of other immune cells. It has been demonstrated that, in a lean state, TH2 cells, Treg cells, natural killer T cells, or eosinophils contribute to the M2 activation of macrophages by secreting IL-4 or IL-10. In contrast, obesity causes alteration of the constituent immune cells, in which TH1 cells, B cells, neutrophils, or mast cells induce M1 activation of macrophages by the elevated secretion of TNFα and IFNγ. Increased secretion of TNFα and free fatty acids from hypertrophied adipocytes also contributes to the M1 activation of macrophages. Since obesity-induced insulin resistance is established by macrophage infiltration and the activation of immune cells inside tissues, identification of the factors that regulate accumulation and the intracellular signaling cascades that define polarization of M1/M2 would be indispensable. Regulation of these factors would lead to the pharmacological inhibition of obesity-induced insulin resistance. In this review, we introduce molecular mechanisms relevant to the pathophysiology and review the most recent studies of clinical applications targeting chronic inflammation. PMID:23964268

  8. Socioeconomic inequality in abdominal obesity among older people in Purworejo District, Central Java, Indonesia - a decomposition analysis approach.

    PubMed

    Pujilestari, Cahya Utamie; Nyström, Lennarth; Norberg, Margareta; Weinehall, Lars; Hakimi, Mohammad; Ng, Nawi

    2017-12-12

    Obesity has become a global health challenge as its prevalence has increased globally in recent decades. Studies in high-income countries have shown that obesity is more prevalent among the poor. In contrast, obesity is more prevalent among the rich in low- and middle-income countries, hence requiring different focal points to design public health policies in the latter contexts. We examined socioeconomic inequalities in abdominal obesity in Purworejo District, Central Java, Indonesia and identified factors contributing to the inequalities. We utilised data from the WHO-INDEPTH Study on global AGEing and adult health (WHO-INDEPTH SAGE) conducted in the Purworejo Health and Demographic Surveillance System (HDSS) in Purworejo District, Indonesia in 2010. The study included 14,235 individuals aged 50 years and older. Inequalities in abdominal obesity across wealth groups were assessed separately for men and women using concentration indexes. Decomposition analysis was conducted to assess the determinants of socioeconomic inequalities in abdominal obesity. Abdominal obesity was five-fold more prevalent among women than in men (30% vs. 6.1%; p < 0.001). The concentration index (CI) analysis showed that socioeconomic inequalities in abdominal obesity were less prominent among women (CI = 0.26, SE = 0.02, p < 0.001) compared to men (CI = 0.49, SE = 0.04, p < 0.001). Decomposition analysis showed that physical labour was the major determinant of socioeconomic inequalities in abdominal obesity among men, explaining 47% of the inequalities, followed by poor socioeconomic status (31%), ≤ 6 years of education (15%) and current smoking (11%). The three major determinants of socioeconomic inequalities in abdominal obesity among women were poor socio-economic status (48%), physical labour (17%) and no formal education (16%). Abdominal obesity was more prevalent among older women in a rural Indonesian setting. Socioeconomic inequality in

  9. Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity.

    PubMed

    Federici, M; Porzio, O; Lauro, D; Borboni, P; Giovannone, B; Zucaro, L; Hribal, M L; Sesti, G

    1998-08-01

    We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

  10. Effects of exercise amount and intensity on abdominal obesity and glucose tolerance in obese adults: a randomized trial.

    PubMed

    Ross, Robert; Hudson, Robert; Stotz, Paula J; Lam, Miu

    2015-03-03

    Exercise reduces obesity and related glucose tolerance, but whether increasing exercise intensity offers additional benefit at fixed exercise amounts is unknown. To determine the separate effects of exercise amount and intensity on abdominal obesity and glucose tolerance. 24-week, single-center, parallel-group trial from 2009 to 2013. (ClinicalTrials.gov: NCT00955071). Kingston, Ontario, Canada. 300 abdominally obese adults. Control (no exercise) (n = 75) or 5 weekly sessions of low-amount, low-intensity exercise (LALI) (180 and 300 kcal/session for women and men, respectively, at 50% of maximum oxygen consumption [V̇o2peak]) (n = 73); high-amount, low-intensity exercise (HALI) (360 and 600 kcal/session, respectively, at 50% of V̇o2peak) (n = 76); or high-amount, high-intensity exercise (HAHI) (360 and 600 kcal/session, respectively, at 75% of V̇o2peak) (n = 76). Daily unsupervised physical activity and sedentary time were measured by accelerometer. Waist circumference and 2-hour glucose level (primary outcomes) and cardiorespiratory fitness and measures of insulin action (secondary measurements). 217 participants (72.3%) completed the intervention. Mean exercise time in minutes per session was 31 (SD, 4.4) for LALI, 58 (SD, 7.6) for HALI, and 40 (SD, 6.2) for HAHI. Daily unsupervised physical activity and sedentary time did not change in any exercise group versus control (P > 0.33). After adjustment for age and sex in a linear mixed model, reductions in waist circumference were greater in the LALI (-3.9 cm [95% CI, -5.6 to -2.3 cm]; P < 0.001), HALI (-4.6 cm [CI, -6.2 to -3.0 cm]; P < 0.001), and HAHI (-4.6 cm [CI, -6.3 to -2.9 cm]; P < 0.001) groups than the control group but did not differ among the exercise groups (P > 0.43). After adjustment for covariates, reductions in 2-hour glucose level were greater in the HAHI group (-0.7 mmol/L [-12.5 mg/dL] [CI, -1.3 to -0.1 mmol/L {-23.5 to -1.5 mg/dL}]; P = 0.027) than the control group but did not differ for the

  11. Abdominal obesity: a marker of ectopic fat accumulation.

    PubMed

    Smith, Ulf

    2015-05-01

    In the early 1980s, we analyzed the metabolic profile of 930 men and women and concluded that an abdominal distribution of fat for a given BMI is associated with increased insulin resistance and risk of developing type 2 diabetes and cardiovascular disease. The correlation between abdominal fat and metabolic dysfunction has since been validated in many studies, and waist circumference is now a criterion for the diagnosis of metabolic syndrome. Several mechanisms for this relationship have been postulated; however, we now know that visceral fat is only one of many ectopic fat depots used when the subcutaneous adipose tissue cannot accommodate excess fat because of its limited expandability.

  12. Epicardial adipose tissue, hepatic steatosis and obesity.

    PubMed

    Cikim, A Sertkaya; Topal, E; Harputluoglu, M; Keskin, L; Zengin, Z; Cikim, K; Ozdemir, R; Aladag, M; Yologlu, S

    2007-06-01

    Hepatic steatosis is a common companion of obesity. Moreover, the measurement of epicardial adipose tissue (EAT) has been reported to be related with both obesity and insulin resistance. Therefore, we aimed to evaluate the relationship between hepatic steatosis, EAT and insulin resistance in obese patients. Sixty-three obese subjects were enrolled in the study. Patients were divided into 3 groups according to body mass index (BMI) as follows: 20 patients with 30 < or = BMI < 35 kg/m2 (Group 1, mean age 39.3+/-12.9 yr), 25 patients with 35 < or = BMI < 40 kg/m2 (Group 2, mean age 41.7+/-9.3 yr), and 18 patients with BMI > or = 40 kg/m2 (Group 3, mean age 36.8+/-13.9 yr). EAT and grade of hepatic steatosis were assessed sonographically. Anthropometrical measurements were assessed with the foot-to-foot bioelectrical impedance analysis. Insulin resistance was assessed according to basal insulin, quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment (HOMA) equations. Although EAT was similarly higher in both groups 2 and 3, these groups were found to be similar in terms of the grade of hepatic steatosis. Both EAT and the grade of hepatic steatosis were correlated with whole body fat mass, abdominal adiposity, insulin resistance, and triglyceridemia but waist circumference was the only factor affecting EAT thickness. Highly sensitive C-reactive protein (hsCRP) was the only metabolic parameter that was significantly higher in Group 3 than in Group 1 (p=0.02). Hepatic steatosis should be assessed as a valuable predictor that reflects the increments of whole body fat mass as well as abdominal adiposity. However, in an attempt to demonstrate marginal differences between patients with similar obesity levels, epicardial adipose tissue appears to be a more sensitive marker compared to hepatic steatosis.

  13. Potential epigenetic biomarkers of obesity-related insulin resistance in human whole-blood.

    PubMed

    Day, Samantha E; Coletta, Richard L; Kim, Joon Young; Garcia, Luis A; Campbell, Latoya E; Benjamin, Tonya R; Roust, Lori R; De Filippis, Elena A; Mandarino, Lawrence J; Coletta, Dawn K

    2017-04-03

    Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance. Whole-blood was obtained from lean (n = 10; BMI = 23.6 ± 0.7 kg/m 2 ) and obese (n = 10; BMI = 34.4 ± 1.3 kg/m 2 ) participants in combination with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing on genomic DNA isolated from the blood. We identified 49 differentially methylated cytosines (DMCs; q < 0.05) that were altered in obese compared with lean participants. We identified 2 sites (Chr.21:46,957,981 and Chr.21:46,957,915) in the 5' untranslated region of solute carrier family 19 member 1 (SLC19A1) with decreased methylation in obese participants (lean 0.73 ± 0.11 vs. obese 0.09 ± 0.05; lean 0.68 ± 0.10 vs. obese 0.09 ± 0.05, respectively). These 2 DMCs identified by obesity were also significantly predicted by insulin sensitivity (r = 0.68, P = 0.003; r = 0.66; P = 0.004). In addition, we performed a differentially methylated region (DMR) analysis and demonstrated a decrease in methylation of Chr.21:46,957,915-46,958,001 in SLC19A1 of -34.9% (70.4% lean vs. 35.5% obese). The decrease in whole-blood SLC19A1 methylation in our obese participants was similar to the change observed in skeletal muscle (Chr.21:46,957,981, lean 0.70 ± 0.09 vs. obese 0.31 ± 0.11 and Chr.21:46,957,915, lean 0.72 ± 0.11 vs. obese 0.31 ± 0.13). Pyrosequencing analysis further demonstrated a decrease in methylation at Chr.21:46,957,915 in both whole-blood (lean 0.71 ± 0

  14. Insulin Resistance and Hunger in Childhood Obesity: A Patient and Physician's Perspective.

    PubMed

    Scinta, Wendy; Bayes, Harold; Smith, Nicole

    2017-10-01

    This article is co-authored by the mother of a child with obesity and insulin resistance, who gives her perspective. It is also co-authored by the treating Obesity Medicine clinician and an investigator in obesity clinical research (both certified in Obesity Medicine), who give their perspectives. The discussion focuses upon the potential clinical use of metformin in managing young patients with obesity and insulin resistance. The article integrates what is scientifically known about the mechanisms of actions of metformin and how these mechanisms are reflected in the clinical response of young patients.

  15. Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice.

    PubMed Central

    Heydrick, S J; Jullien, D; Gautier, N; Tanti, J F; Giorgetti, S; Van Obberghen, E; Le Marchand-Brustel, Y

    1993-01-01

    Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway. Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions. Insulin did not affect total PI3K activity. Both the antiPTyr-PI3K stimulation and activation of insulin receptor tyrosine kinase were dependent on hormone concentration. In muscles from obese, insulin-resistant mice, there was a 40-60% decrease in antiPTyr-PI3K activity after 2 min of insulin that was present equally in the cytosolic and membrane fractions. A significant reduction in insulin sensitivity was also observed. The defect appears to result from alterations in both insulin receptor and postreceptor signaling. Starvation of obese mice for 48 h, which is known to reverse insulin resistance, normalized the insulin response of both PI3K and the receptor tyrosine kinase. The results demonstrate that: (a) antiPTyr-PI3K activity is responsive to insulin in mouse skeletal muscle, (b) both the insulin responsiveness and sensitivity of this activity are blunted in insulin-resistant muscles from obese mice, (c) these alterations result from a combination of insulin receptor and postreceptor defects, and (d) starvation restores normal insulin responses. Images PMID:8386184

  16. NK cells link obesity-induced adipose stress to inflammation and insulin resistance.

    PubMed

    Wensveen, Felix M; Jelenčić, Vedrana; Valentić, Sonja; Šestan, Marko; Wensveen, Tamara Turk; Theurich, Sebastian; Glasner, Ariella; Mendrila, Davor; Štimac, Davor; Wunderlich, F Thomas; Brüning, Jens C; Mandelboim, Ofer; Polić, Bojan

    2015-04-01

    An important cause of obesity-induced insulin resistance is chronic systemic inflammation originating in visceral adipose tissue (VAT). VAT inflammation is associated with the accumulation of proinflammatory macrophages in adipose tissue, but the immunological signals that trigger their accumulation remain unknown. We found that a phenotypically distinct population of tissue-resident natural killer (NK) cells represented a crucial link between obesity-induced adipose stress and VAT inflammation. Obesity drove the upregulation of ligands of the NK cell-activating receptor NCR1 on adipocytes; this stimulated NK cell proliferation and interferon-γ (IFN-γ) production, which in turn triggered the differentiation of proinflammatory macrophages and promoted insulin resistance. Deficiency of NK cells, NCR1 or IFN-γ prevented the accumulation of proinflammatory macrophages in VAT and greatly ameliorated insulin sensitivity. Thus NK cells are key regulators of macrophage polarization and insulin resistance in response to obesity-induced adipocyte stress.

  17. Expression of the central obesity and Type 2 Diabetes mellitus genes is associated with insulin resistance in young obese children.

    PubMed

    Skoczen, S; Wojcik, M; Fijorek, K; Siedlar, M; Starzyk, J B

    2015-04-01

    The assessment of the health consequences associated with obesity in young children is challenging. The aims of this study were: (1) to compare insulin resistance indices derived from OGTT in obese patients and healthy control (2) to analyze central obesity and Type 2 Diabetes genes expression in obese children, with special attention to the youngest group (< 10 years old). The study included 49 children with obesity (median age 13.5 years old), and 25 healthy peers. Biochemical blood tests and expression of 11 central obesity and 33 Type 2 Diabetes genes was assessed. A significant difference in insulin resistance between obese and non-obese adolescents was observed in all studied indices (mean values of the insulin levels: 24.9 vs. 9.71 mIU/L in T0, 128 vs. 54.7 mIU/L in T60 and 98.7 vs. 41.1 mIU/L in T120 respectively; AUC: 217 vs. 77.2 ng/ml*h, mean values of B% (state beta cell function), S% (insulin sensitivity), and IR were 255 (±97) vs. 135 (±37.8), 46.6 (±37.3) vs. 84.2 (±29.6) and 3 (±1.55) vs. 1.36 (±0,56); HIS, WBIS and ISIBel median 3.89, 44.7, 0.73 vs. 8.57, 110, 2.25. All comparisons differed significantly p<0.001). Moreover, insulin sensitivity was significantly better in the older obese group (>10 years old): median AUC 239 vs. 104 ng/ml*h, and HIS, WBIS and ISIBel 3.57, 38, 0.67 vs. 6.23, 75.6, 1.87 respectively in the obese older compared to the obese younger subgroup, p<0.05. The expression of 64% of the central obesity genes and 70% of Type 2 Diabetes genes was higher in the obese compared to control groups. The differences were more pronounced in the younger obese group. Insulin resistance may develop in early stage of childhood obesity and in very young children may be associated with higher expression of the central obesity and Type 2 Diabetes genes. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Effects of losartan on whole-body, skeletal muscle, and vascular insulin responses in obesity/insulin resistance without hypertension

    PubMed Central

    Lteif, AA; Chisholm, RL; Gilbert, K; Considine, RV; Mather, KJ

    2011-01-01

    Aims Renin-angiotensin system antagonists have been found to improve glucose metabolism in obese hypertensive and type 2 diabetic subjects. The mechanism of these effects is not well understood. We hypothesized that the angiotensin receptor antagonist losartan would improve insulin-mediated vasodilation, and thereby improve insulin-stimulated glucose uptake in skeletal muscle of insulin resistant subjects. Materials and Methods We studied subjects with obesity and insulin resistance but without hypertension, hypercholesterolemia or dysglycemia (age 39.0±9.6 yrs [mean±SD], BMI 33.2±5.9 kg/m2, BP 115.8±12.2/70.9±7.2 mmHg, LDL 2.1±0.5 mmol/L). Subjects were randomized to 12 weeks’ double-blind treatment with losartan 100 mg once daily (n=9) or matching placebo (n=8). Before and after treatment, under hyperinsulinemic euglycemic clamp conditions we measured whole-body insulin stimulated glucose disposal, insulin-mediated vasodilation, and insulin-stimulated leg glucose uptake by the limb balance technique. Results Whole-body insulin-stimulated glucose disposal was not significantly increased by losartan. Insulin-mediated vasodilation was augmented following both treatments (increase in leg vascular conductance: pre-treatment 0.7±0.3 L*min−1*mmHg−1[losartan, mean ±SEM] and 0.9±0.3 [placebo], post-treatment 1.0±0.4 [losartan] and 1.3±0.6 [placebo]) but not different between treatment groups (p=0.53). Insulin’s action to augment NO production and to augment endothelium-dependent vasodilation were also not improved. Leg glucose uptake was not significantly changed by treatments, and not different between groups (p=0.11). Conclusions These findings argue against the hypothesis that losartan might improve skeletal muscle glucose metabolism by improving insulin-mediated vasodilation in normotensive insulin resistant obese subjects. The metabolic benefits of angiotensin receptor blockers may require the presence of hypertension in addition to obesity

  19. Insulin-Like Growth Factors and Metabolic Syndrome in Obese Children.

    PubMed

    Inzaghi, Elena; Baldini Ferroli, Barbara; Fintini, Danilo; Grossi, Armando; Nobili, Valerio; Cianfarani, Stefano

    2017-01-01

    Insulin-like growth factor (IGF)-I is related to cardiometabolic risk in adults, whereas the metabolic role of IGF-II is unclear. The aim of this study was to assess IGFs in obese children and correlate them with metabolic syndrome (MetS) components. This is a retrospective study including 574 obese children (11.34 ± 3.16 years). All subjects underwent complete anthropometry and biochemical assessment. In a subgroup of 136 subjects, body composition was evaluated. IGF-I was measured in 300 obese subjects and IGF-II in 77 obese and 15 lean children. 177 subjects were divided according to the presence of 1 or more MetS criteria: group 1, subjects with 1 MetS criterion; group 2, subjects with 2 components; and group 3, subjects with MetS diagnosis. IGF-I, IGF-II, and IGF-I/insulin-like growth factor-binding protein-3 ratio were not different among subjects with an increasing number of MetS criteria and were not associated with single components of MetS as well as with body composition parameters. In children younger than 10 years, IGF-I directly correlated with high-density lipoprotein cholesterol (p < 0.005) even after controlling for confounders. IGF-II was significantly higher in obese children and correlated with parameters of insulin sensitivity (p < 0.05). IGFs were neither related to MetS nor to body composition parameters in obese children. Further studies are needed to clarify the mechanisms underlying the relationship between IGF-II and insulin sensitivity. © 2017 S. Karger AG, Basel.

  20. Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance.

    PubMed

    Ketel, Iris J G; Stehouwer, Coen D A; Serné, Erik H; Korsen, Ted J M; Hompes, Peter G A; Smulders, Yvo M; de Jongh, Renate T; Homburg, Roy; Lambalk, Cornelis B

    2008-09-01

    Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. The objective of the study was to investigate whether insulin sensitivity and insulin's effects on the microcirculation are impaired in normal-weight and obese women with PCOS. Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia. Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity). Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups. PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are

  1. Obesity-related insulin resistance in adolescents: a systematic review and meta-analysis of observational studies.

    PubMed

    Thota, P; Perez-Lopez, F R; Benites-Zapata, V A; Pasupuleti, V; Hernandez, A V

    2017-03-01

    Insulin resistance is common among obese adolescents; however, the extent of this problem is not clear. We conducted a systematic review of PubMed-Medline, CINAHL, The Web of Science, EMBASE and Scopus for observational studies evaluating components defining insulin resistance (insulin, C-peptide and homeostatic model assessment-insulin resistance [HOMA-IR]) in obese adolescents (12-18 years) versus non-obese adolescents. Our systematic review and meta-analysis followed the PRISMA guidelines. Data were combined using a random-effects model and summary statistics were calculated using the mean differences (MDs). 31 studies were included (n = 8655). In 26 studies, fasting insulin levels were higher in obese adolescents when compared to non-obese adolescents (MD = 64.11 pmol/L, 95%CI 49.48-78.75, p < 0.00001). In three studies, fasting C-peptide levels were higher in obese adolescents when compared to non-obese adolescents (MD = 0.29 nmol/L, 95%CI 0.22-0.36, p < 0.00001). In 24 studies, HOMA-IR values were higher in obese adolescents when compared to non-obese adolescents (MD = 2.22, 95%CI 1.78-2.67, p < 0.00001). Heterogeneity of effects among studies was moderate to high. Subgroup analyses showed similar results to the main analyses. Circulating insulin and C-peptide levels and HOMA-IR values were significantly higher in obese adolescents compared to those non-obese.

  2. Serum Fatty Acids, Desaturase Activities and Abdominal Obesity – A Population-Based Study of 60-Year Old Men and Women

    PubMed Central

    Alsharari, Zayed D.; Risérus, Ulf; Leander, Karin; Sjögren, Per; Carlsson, Axel C.; Vikström, Max; Laguzzi, Federica; Gigante, Bruna; Cederholm, Tommy; De Faire, Ulf; Hellénius, Mai-Lis

    2017-01-01

    Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA-desaturase and Δ6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19–1.76), 4.06 (3.27–5.05), and 3.07 (2.51–3.75), respectively. Linoleic acid, α-linolenic acid, docohexaenoic acid, and Δ5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32–0.48), 0.74 (0.61–0.89), 0.76 (0.62–0.93), and 0.40 (0.33–0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across

  3. A randomized, double blind, cross-over, placebo-controlled clinical trial to assess the effects of Candesartan on the insulin sensitivity on non diabetic, non hypertense subjects with dysglyce mia and abdominal obesity. "ARAMIA"

    PubMed Central

    López-Jaramillo, Patricio; Pradilla, Lina P; Lahera, Vicente; Sieger, Federico A Silva; Rueda-Clausen, Christian F; Márquez, Gustavo A

    2006-01-01

    Candesartan, could improve the HOMA index, the response to the oral glucose tolerance test and reduce the plasma levels of adipoquines, oxidative stress and prothrombotic markers, in non diabetic, non hypertense subjects with dysglycemia and abdominal obesity, recruited from a population at high risk of developing insulin resistance. These effects are independent of the changes in arterial blood pressure. Trial registration: NCT00319202 PMID:16959033

  4. [Diagnosis of insulin resistance by indirect methods in obese school children].

    PubMed

    Angulo, Nerkis; de Szarvas, Sobeida Barbella; Mathison, Yaira; Hadad, Erika; González, Dora; Hernández, Ana; Guevara, Harold

    2013-06-01

    Obesity leads to a deterioration of glucose tolerance and the action of insulin. The purpose of this study was to determine insulin resistance (IR) by indirect methods, and its correlation with clinical, anthropometric and biochemical variables in obese normoglycemic school children. This was a descriptive-correlational study of 72 school prepubescent children, who attended the ambulatory "El Concejo" of the University of Carabobo (UC) and at the Gastroenterology and Pediatric Nutrition service of the city hospital "Enrique Tejera" (CHET), in Valencia, Venezuela, between January-April 2011. exogenous obesity. We assessed personal and family history, presence of Acanthosis Nigricans and nutritional and biochemical status. We found a higher percentage of IR, through the use of the QUICKI method (66.7%), followed by the HOMA (55.6%) and basal insulin (45.9%). The mean (chi) indexes of body mass and waist circumference were significantly greater (p < 0.05) in patients with IR, by HOMA and QUICKI techniques. The QUICKI method detected significant differences (p < 0.05) in the values of glycemia, basal insulin and postprandial insulin, among patients with diminished and normal insulin sensitivities. While HOMA, detected these differences (p < 0.05) in the values of glycemia and basal insulin. A statistically significant relationship was observed (p < 0.05), between the presence of Acanthosis Nigricans and IR, by the HOMA, QUICKI and basal insulin methods. In conclusion, the evaluated techniques, QUICKI, HOMA and basal insulin indexes, were most effective for detecting the IR.

  5. Use of insulin sensitizers for the treatment of major depressive disorder: a pilot study of pioglitazone for major depression accompanied by abdominal obesity.

    PubMed

    Kemp, David E; Ismail-Beigi, Faramarz; Ganocy, Stephen J; Conroy, Carla; Gao, Keming; Obral, Sarah; Fein, Elizabeth; Findling, Robert L; Calabrese, Joseph R

    2012-02-01

    This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder. In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15 mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference>35 in. in women and >40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (≥25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months. Pioglitazone decreased depression symptom severity from a total IDS score of 40.3±1.8 to 19.2±1.8 at Week 12 (p<.001). Among partial responders (≥25% decrease in IDS total score), an improvement in depressive symptoms was maintained during an additional 3-month extension phase (total duration=24 weeks) according to IDS total scores (p<.001). Patients experienced a reduction in insulin resistance from baseline to Week 12 according to the log homeostasis model assessment (-0.8±0.75; p<.001) and a significant reduction in inflammation as measured by log highly- sensitive C-reactive protein (-0.87±0.72; p<.001). During the current episode, the majority of participants (74%, n=17), had already failed at least one antidepressant trial. The most common side effects were headache and dizziness; no patient discontinued due to side effects. These data are limited by a small sample size and an open-label study design with no placebo control. Although preliminary, pioglitazone appears to reduce depression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. Larger, placebo-controlled studies are indicated. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women.

    PubMed

    Stull, April J; Cash, Katherine C; Johnson, William D; Champagne, Catherine M; Cefalu, William T

    2010-10-01

    Dietary supplementation with whole blueberries in a preclinical study resulted in a reduction in glucose concentrations over time. We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women. A double-blinded, randomized, and placebo-controlled clinical study design was used. After screening to resolve study eligibility, baseline (wk 0) insulin sensitivity was measured on 32 obese, nondiabetic, and insulin-resistant subjects using a high-dose hyperinsulinemic-euglycemic clamp (insulin infusion of 120 mU(861 pmol)⋅m(-2)⋅min(-1)). Serum inflammatory biomarkers and adiposity were measured at baseline. At the end of the study, insulin sensitivity, inflammatory biomarkers, and adiposity were reassessed. Participants were randomized to consume either a smoothie containing 22.5 g blueberry bioactives (blueberry group, n = 15) or a smoothie of equal nutritional value without added blueberry bioactives (placebo group, n = 17) twice daily for 6 wk. Both groups were instructed to maintain their body weight by reducing ad libitum intake by an amount equal to the energy intake of the smoothies. Participants' body weights were evaluated weekly and 3-d food records were collected at baseline, the middle, and end of the study. The mean change in insulin sensitivity improved more in the blueberry group (1.7 ± 0.5 mg⋅kg FFM(-1)⋅min(-1)) than in the placebo group (0.4 ± 0.4 mg⋅kg FFM(-1)⋅min(-1)) (P = 0.04). Insulin sensitivity was enhanced in the blueberry group at the end of the study without significant changes in adiposity, energy intake, and inflammatory biomarkers. In conclusion, daily dietary supplementation with bioactives from whole blueberries improved insulin sensitivity in obese, nondiabetic, and insulin-resistant participants.

  7. Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance

    USDA-ARS?s Scientific Manuscript database

    Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammat...

  8. Household food insecurity is associated with abdominal but not general obesity among Iranian children.

    PubMed

    Jafari, Fateme; Ehsani, Simin; Nadjarzadeh, Azadeh; Esmaillzadeh, Ahmad; Noori-Shadkam, Mahmood; Salehi-Abargouei, Amin

    2017-04-21

    Childhood obesity is increasing all over the world. Food insecurity is mentioned as a possible risk factor; however, previous studies have led to inconsistent results in different societies while data are lacking for the Middle East. We aimed to investigate the relationship between food insecurity and general or abdominal obesity in Iranian children in a cross-sectional study. Anthropometric data including height, weight, and waist circumference were measured by trained nutritionists. General and abdominal obesity were defined based on world health organization (WHO) and Iranian reference curves for age and gender, respectively. Radimer/Cornell food security questionnaire was filled by parents. Data about the physical activity of participants, family socio-economic status, parental obesity and data about perinatal period were also gathered using self-administered questionnaires. Logistic regression was incorporated to investigate the association between food insecurity and obesity in crude and multi-variable adjusted models. A total of 587 children aged 9.30 ± 1.49 years had complete data for analysis. Food insecurity at household level was significantly associated with abdominal obesity (odds ratio (OR) = 1.54; confidence interval (CI):1.01-2.34, p <0.05) and the relationship remained significant after adjusting for all potential confounding variables (OR = 2.02; CI:1.01-4.03, p <0.05). Food insecurity was associated with general obesity neither in crude analysis and multi-variable adjusted models. The slight levels of food insecurity might increase the likelihood of abdominal obesity in Iranian children and macroeconomic policies to improve the food security are necessary. Large-scale prospective studies, particularly in the Middle East, are highly recommended to confirm our results.

  9. Insulin and leptin relations in obesity: a multimedia approach.

    PubMed

    Yokaichiya, Daniela K; Galembeck, Eduardo; Torres, Bayardo B; Da Silva, José Antônio; de Araujo, Daniele R

    2008-09-01

    Obesity has been recognized as a worldwide public health problem. It significantly increases the chances of developing several diseases, including Type II diabetes. The roles of insulin and leptin in obesity involve reactions that can be better understood when they are presented step by step. The aim of this work was to design software with data from some of the most recent publications on obesity, especially those concerning the roles of insulin and leptin in this metabolic disturbance. The most notable characteristic of this software is the use of animations representing the cellular response together with the presentation of recently discovered mechanisms on the participation of insulin and leptin in processes leading to obesity. The software was field tested in the Biochemistry of Nutrition web-based course. After using the software and discussing its contents in chatrooms, students were asked to answer an evaluation survey about the whole activity and the usefulness of the software within the learning process. The teaching assistants (TA) evaluated the software as a tool to help in the teaching process. The students' and TAs' satisfaction was very evident and encouraged us to move forward with the software development and to improve the use of this kind of educational tool in biochemistry classes.

  10. Effect of FTO rs9939609 variant on insulin resistance in obese female adolescents.

    PubMed

    Iskandar, Kristy; Patria, Suryono Yudha; Huriyati, Emy; Luglio, Harry Freitag; Julia, Madarina; Susilowati, Rina

    2018-05-15

    FTO rs9939609 variant has been shown to be associated with insulin resistance in Caucasian children. However, studies in Asia show inconsistent findings. We investigated the association between FTO rs9939609 polymorphisms and insulin resistance in obese female adolescents in Indonesia, a genetically distinct group within Asia. A total of 78 obese female adolescents participated in this study. The risk allele (A) frequency of FTO rs9939609 variant in Indonesian obese female adolescence was 44.2%. The frequency of insulin resistance was higher in the subjects with AA (54.6%) or AT (59.6%) than the subject with TT genotype (50%), but did not statistically different (p = 0.81 and p = 0.47, respectively). The insulin resistance rate was also higher in the risk allele (A) than the non-risk allele (T) subjects (0.58 vs. 0.55), but did not statistically different (p = 0.75). There was no association between FTO rs9939609 variant and body mass index, fasting glucose level, fasting insulin level, homeostatic model assessment of insulin resistance, and waist circumference (p > 0.05). In conclusion, FTO rs9939609 variant may not be associated with insulin resistance in Indonesian obese female adolescents. A multicenter study with a larger sample size is needed to clarify these findings.

  11. Prevalence of Prediabetes and Abdominal Obesity Among Healthy-Weight Adults: 18-Year Trend.

    PubMed

    Mainous, Arch G; Tanner, Rebecca J; Jo, Ara; Anton, Stephen D

    2016-07-01

    Trends in sedentary lifestyle may have influenced adult body composition and metabolic health among individuals at presumably healthy weights. This study examines the nationally representative prevalence of prediabetes and abdominal obesity among healthy-weight adults in 1988 through 2012. We analyzed the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES for the years 1999 to 2012, focusing on adults aged 20 years and older who have a body mass index (BMI) of 18.5 to 24.99 and do not have diabetes, either diagnosed or undiagnosed. We defined prediabetes using glycated hemoglobin (HbA1c) level ranges from 5.7% to 6.4%, as specified by the American Diabetes Association. Abdominal obesity was measured by waist circumference and waist-to-height ratio. The prevalence of prediabetes among healthy-weight adults, aged 20 years and older and without diagnosed or undiagnosed diabetes, increased from 10.2% in 1988-1994 to 18.5% in 2012. Among individuals aged 45 years and older, the prevalence of prediabetes increased from 22.0% to 33.1%. The percentage of adults aged 20 years and older with an unhealthy waist circumference increased from 5.6% in 1988-1994 to 7.6% in 2012. The percentage of individuals with an unhealthy waist-to-height ratio increased from 27.2% in 1988-1994 to 33.7% in 2012. Adjusted models found that measures of abdominal obesity were not independent predictors of prediabetes among adults with a healthy BMI. Among individuals within a healthy BMI range, the prevalence of prediabetes and abdominal obesity has substantially increased. Abdominal obesity does not appear to be the primary cause of the increase. © 2016 Annals of Family Medicine, Inc.

  12. Prevalence of Prediabetes and Abdominal Obesity Among Healthy-Weight Adults: 18-Year Trend

    PubMed Central

    Mainous, Arch G.; Tanner, Rebecca J.; Jo, Ara; Anton, Stephen D.

    2016-01-01

    PURPOSE Trends in sedentary lifestyle may have influenced adult body composition and metabolic health among individuals at presumably healthy weights. This study examines the nationally representative prevalence of prediabetes and abdominal obesity among healthy-weight adults in 1988 through 2012. METHODS We analyzed the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES for the years 1999 to 2012, focusing on adults aged 20 years and older who have a body mass index (BMI) of 18.5 to 24.99 and do not have diabetes, either diagnosed or undiagnosed. We defined prediabetes using glycated hemoglobin (HbA1c) level ranges from 5.7% to 6.4%, as specified by the American Diabetes Association. Abdominal obesity was measured by waist circumference and waist-to-height ratio. RESULTS The prevalence of prediabetes among healthy-weight adults, aged 20 years and older and without diagnosed or undiagnosed diabetes, increased from 10.2% in 1988–1994 to 18.5% in 2012. Among individuals aged 45 years and older, the prevalence of prediabetes increased from 22.0% to 33.1%. The percentage of adults aged 20 years and older with an unhealthy waist circumference increased from 5.6% in 1988–1994 to 7.6% in 2012. The percentage of individuals with an unhealthy waist-to-height ratio increased from 27.2% in 1988–1994 to 33.7% in 2012. Adjusted models found that measures of abdominal obesity were not independent predictors of prediabetes among adults with a healthy BMI. CONCLUSIONS Among individuals within a healthy BMI range, the prevalence of prediabetes and abdominal obesity has substantially increased. Abdominal obesity does not appear to be the primary cause of the increase. PMID:27401417

  13. Role of immune cells in obesity induced low grade inflammation and insulin resistance.

    PubMed

    Asghar, Ambreen; Sheikh, Nadeem

    2017-05-01

    The frequency of obesity is enormously growing worldwide. Obesity results when energy intake exceeds, energy expenditure. Excess adiposity is a major risk factor in the progress of various metabolic disorders accounting insulin resistance, hypertension, Type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovarian disease and several types of cancers. Obesity is characterized by pro-inflammatory condition in which hypertrophied adipose tissue along with immune cells contribute to increase the level of pro-inflammatory cytokines. Immune cells are the key players in inducing low grade chronic inflammation in obesity and are main factor responsible for pathogenesis of insulin resistance resulting Type 2 diabetes. The current review is aimed to investigate the mechanism of pro-inflammatory responses and insulin resistance involving immune cells and their products in obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Influence of insulin on beta-endorphin plasma levels in obese and normal weight subjects.

    PubMed

    Brunani, A; Pincelli, A I; Pasqualinotto, L; Tibaldi, A; Baldi, G; Scacchi, M; Fatti, L M; Cavagnini, F

    1996-08-01

    To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

  15. Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients.

    PubMed

    Jaganjac, Morana; Almuraikhy, Shamma; Al-Khelaifi, Fatima; Al-Jaber, Mashael; Bashah, Moataz; Mazloum, Nayef A; Zarkovic, Kamelija; Zarkovic, Neven; Waeg, Georg; Kafienah, Wael; Elrayess, Mohamed A

    2017-08-01

    Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery. Levels of 4-HNE protein adducts, adipocyte size and number of macrophages were determined within these tissues by immunohistochemistry. Adipogenic capacity and gene expression profiles were assessed in preadipocytes derived from these tissues in relation to insulin resistance and in response to 4-HNE, metformin or combined metformin and insulin treatment. Preadipocytes isolated from insulin resistant (IR) and T2DM individuals exhibited lower adipogenesis, marked by upregulation of anti-adipogenic genes, compared to preadipocytes derived from insulin sensitive (IS) individuals. Impaired adipogenesis was also associated with increased 4-HNE levels, smaller adipocytes and greater macrophage presence in the adipose tissues. Within the T2DM group, preadipocytes from combined metformin and insulin treated subset showed better in vitro adipogenesis compared to metformin alone, which was associated with less presence of macrophages and 4-HNE in the adipose tissues. Treatment of preadipocytes in vitro with 4-HNE reduced their adipogenesis and increased proliferation, even in the presence of metformin, which was partially rescued by the presence of insulin. This study reveals involvement of 4-HNE in the impaired OM adipogenesis-associated with insulin resistance and T2DM and provides a proof of concept that this impairment can be reversed by the synergistic action of insulin and metformin. Further studies are

  16. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.

    PubMed

    Pasquali, R; Gambineri, A; Biscotti, D; Vicennati, V; Gagliardi, L; Colitta, D; Fiorini, S; Cognigni, G E; Filicori, M; Morselli-Labate, A M

    2000-08-01

    Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was

  17. The effect of insulin resistance and exercise on the percentage of CD16(+) monocyte subset in obese individuals.

    PubMed

    de Matos, Mariana A; Duarte, Tamiris C; Ottone, Vinícius de O; Sampaio, Pâmela F da M; Costa, Karine B; de Oliveira, Marcos F Andrade; Moseley, Pope L; Schneider, Suzanne M; Coimbra, Cândido C; Brito-Melo, Gustavo E A; Magalhães, Flávio de C; Amorim, Fabiano T; Rocha-Vieira, Etel

    2016-06-01

    Obesity is a low-grade chronic inflammation condition, and macrophages, and possibly monocytes, are involved in the pathological outcomes of obesity. Physical exercise is a low-cost strategy to prevent and treat obesity, probably because of its anti-inflammatory action. We evaluated the percentage of CD16(-) and CD16(+) monocyte subsets in obese insulin-resistant individuals and the effect of an exercise bout on the percentage of these cells. Twenty-seven volunteers were divided into three experimental groups: lean insulin sensitive, obese insulin sensitive and obese insulin resistant. Venous blood samples collected before and 1 h after an aerobic exercise session on a cycle ergometer were used for determination of monocyte subsets by flow cytometry. Insulin-resistant obese individuals have a higher percentage of CD16(+) monocytes (14.8 ± 2.4%) than the lean group (10.0 ± 1.3%). A positive correlation of the percentage of CD16(+) monocytes with body mass index and fasting plasma insulin levels was found. One bout of moderate exercise reduced the percentage of CD16(+) monocytes by 10% in all the groups evaluated. Also, the absolute monocyte count, as well as all other leukocyte populations, in lean and obese individuals, increased after exercise. This fact may partially account for the observed reduction in the percentage of CD16(+) cells in response to exercise. Insulin-resistant, but not insulin-sensitive obese individuals, have an increased percentage of CD16(+) monocytes that can be slightly modulated by a single bout of moderate aerobic exercise. These findings may be clinically relevant to the population studied, considering the involvement of CD16(+) monocytes in the pathophysiology of obesity. Copyright © 2016 John Wiley & Sons, Ltd. Obesity is now considered to be an inflammatory condition associated with many pathological consequences, including insulin resistance. It is proposed that insulin resistance contributes to the aggravation of the

  18. Obese adolescent girls with polycystic ovary syndrome (PCOS) have more severe insulin resistance measured by HOMA-IR score than obese girls without PCOS.

    PubMed

    Sawathiparnich, Pairunyar; Weerakulwattana, Linda; Santiprabhob, Jeerunda; Likitmaskul, Supawadee

    2005-11-01

    The prevalence of obesity in Thai children is increasing. These individuals are at increased risks of metabolic syndrome that includes insulin resistance, type 2 diabetes mellitus (T2DM), polycystic ovary syndrome (PCOS), dyslipidemia and hypertension. PCOS has been known to be associated with insulin resistance. To compare the insulin sensitivity between obese adolescent girls with PCOS and those without PCOS. We reviewed demographic and hormonal data of 6 obese adolescent girls with PCOS and compared with 6 age, weight and BMI-matched non-PCOS controls. Each subject underwent an oral glucose tolerance test. Homeostasis model assessment of insulin resistance score (HOMA-IR score) in obese adolescent girls with PCOS was significantly higher than in girls without PCOS with median and range as follows (16.5 [3.8, 21.8] vs. 4.1 [3.3, 6.9], p = 0.04). Our study demonstrates that obese adolescent girls with PCOS have more severe insulin resistance measured by HOMA-IR score than girls without PCOS independent of the degree of obesity. Since insulin resistance is a metabolic precursor of future cardiovascular diseases, obese adolescent girls with PCOS might be at greater risk of developing cardiovascular disease in later adulthood than their non-PCOS counterparts.

  19. Association between Myeloperoxidase Levels and Risk of Insulin Resistance in Egyptian Obese Women

    PubMed Central

    Zaki, Moushira; Basha, Walaa; Reyad, Hanaa; Mohamed, Ramy; Hassan, Naglaa; Kholousi, Shams

    2018-01-01

    BACKGROUND: Myeloperoxidase (MPO) is an enzyme involved in the pathogenesis of several diseases. AIM: The current study aimed to investigate serum MPO levels in obese Egyptian women and assess its relation with insulin resistance (IR) and other biochemical risk parameters. METHODS: The study included 80 obese women and 50 age-and-sex-matched healthy controls. Insulin resistance (IR) was evaluated by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Serum MPO, fasting glucose, insulin and blood lipids and anthropometry were measured. Obese cases were divided into three groups based on MPO tertiles. ROC analysis was performed to obtain the optimal cut-off values of MPO to predicate IR in obese women. RESULTS: The mean serum MPO was significantly higher in obese cases than controls. Cases in the highest MPO tertile had higher HOMA-IR, blood lipids and pressure levels compared with those in the lower tertile. The cutoff point of MPO was > 87.8 (ng/mL) and area under curves was 0.82 (p < 0.01) for diagnosis of IR. MPO levels were higher in obese Egyptian women than healthy controls. CONCLUSION: Elevation of MPO was associated with abnormal metabolic parameters. MPO might be used as an earlier biomarker for IR and metabolic disturbance in obese women. PMID:29731928

  20. Management of obesity in NIDDM (non-insulin-dependent diabetes mellitus).

    PubMed

    Cheah, J S

    1998-08-01

    Obesity is common in NIDDM; in a cohort of 314 diabetics in Singapore, 44.3% are overweight. Management of obesity in diabetics differs from that in non-diabetics in that it is more urgent; weight maintenance is more difficult and hypoglycaemic medication may cause weight changes. Like in the non-diabetic, management of obesity in diabetic requires a pragmatic and realistic approach. A team approach is required: the help of the nurse educator, the dietitian, behaviour modification therapist, exercise therapist etc are required. A detailed history, careful physical examination and relevant investigations are required to assess the severity of the diabetic state and to exclude an occasional underlying cause of the obesity in the obese NIDDM. Weight loss is urgent in the obese NIDDM, especially those with android obesity. There must be a reduction in caloric intake. Weight loss leads to improvement in the glucose tolerance, insulin sensitivity, reduction in lipid levels and fall in blood pressure in the hypertensive. Exercise is of limited value except in the younger obese NIDDM. Metformin is the hypoglycaemic drug of choice as it leads to consistent weight reduction. The sulphonylureas may cause weight gain. Insulin should be avoided where possible as it causes further weight gain. Other hypoglycaemic agents include Glucobay (alpha-glucosidase inhibitor) and Troglitazone (insulin sensitizer) which do not alter the weight. Orlistat (lipase inhibitor) is promising as it causes reduction of weight, blood-glucose and lipid levels. Anti-obesity drugs (noradrenergic and serotonergic agents) have modest effects on weight reduction in the obese NIDDM; a widely use preparation, Dexfenfluramine (Adifax) has been withdrawn because of side effects. Surgery such as gastric plication is the last resort in treating the morbidly obese NIDDM. The discovery of leptin in 1994 has led to intense research into energy homeostasis in obesity; hopefully this will lead to better treatment of

  1. Dietary Aloe QDM Complex Reduces Obesity-Induced Insulin Resistance and Adipogenesis in Obese Mice Fed a High-Fat Diet.

    PubMed

    Shin, Seulmee; Kim, Seulah; Oh, Hee-Eun; Kong, Hyunseok; Shin, Eunju; Do, Seon-Gil; Jo, Tae Hyung; Park, Young-In; Lee, Chong-Kil; Kim, Kyungjae

    2012-06-01

    Obesity-induced disorders contribute to the development of metabolic diseases such as insulin resistance, fatty liver diseases, and type 2 diabetes (T2D). In this study, we evaluated whether the Aloe QDM complex could improve metabolic disorders related to blood glucose levels and insulin resistance. Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of Aloe QDM complex or pioglitazone (PGZ) or metformin (Met) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Dietary Aloe QDM complex lowered body weight, fasting blood glucose, plasma insulin, and leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Also, Aloe QDM complex significantly enhanced plasma adiponectin levels and insulin sensitivity via AMPK activity in muscles. At the same time, Aloe QDM decreased the mRNA and protein of PPARγ/LXRα and scavenger receptors in white adipose tissue (WAT). Dietary Aloe QDM complex reduces obesity-induced glucose tolerance not only by suppressing PPARγ/LXRα but also by enhancing AMPK activity in the WAT and muscles, both of which are important peripheral tissues affecting insulin resistance. The Aloe QDM complex could be used as a nutritional intervention against T2D.

  2. Dietary Aloe QDM Complex Reduces Obesity-Induced Insulin Resistance and Adipogenesis in Obese Mice Fed a High-Fat Diet

    PubMed Central

    Shin, Seulmee; Kim, Seulah; Oh, Hee-Eun; Kong, Hyunseok; Shin, Eunju; Do, Seon-Gil; Jo, Tae Hyung; Park, Young-In; Lee, Chong-Kil

    2012-01-01

    Obesity-induced disorders contribute to the development of metabolic diseases such as insulin resistance, fatty liver diseases, and type 2 diabetes (T2D). In this study, we evaluated whether the Aloe QDM complex could improve metabolic disorders related to blood glucose levels and insulin resistance. Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of Aloe QDM complex or pioglitazone (PGZ) or metformin (Met) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Dietary Aloe QDM complex lowered body weight, fasting blood glucose, plasma insulin, and leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Also, Aloe QDM complex significantly enhanced plasma adiponectin levels and insulin sensitivity via AMPK activity in muscles. At the same time, Aloe QDM decreased the mRNA and protein of PPARγ/LXRα and scavenger receptors in white adipose tissue (WAT). Dietary Aloe QDM complex reduces obesity-induced glucose tolerance not only by suppressing PPARγ/LXRα but also by enhancing AMPK activity in the WAT and muscles, both of which are important peripheral tissues affecting insulin resistance. The Aloe QDM complex could be used as a nutritional intervention against T2D. PMID:22916045

  3. The Definition and Prevalence of Obesity and Metabolic Syndrome.

    PubMed

    Engin, Atilla

    2017-01-01

    Increase in prevalence of obesity has become a worldwide major health problem in adults, as well as among children and adolescents. Furthermore, total adiposity and truncal subcutaneous fat accumulation during adolescence are positively and independently associated with atherosclerosis at adult ages. Centrally accumulation of body fat is associated with insulin resistance, whereas distribution of body fat in a peripheral pattern is metabolically less important. Obesity is associated with a large decrease in life expectancy. The effect of extreme obesity on mortality is greater among younger than older adults. In this respect, obesity is also associated with increased risk of several cancer types. However, up to 30% of obese patients are metabolically healthy with insulin sensitivity similar to healthy normal weight individuals, lower visceral fat content, and lower intima media thickness of the carotid artery than the majority of metabolically "unhealthy" obese patients.Abdominal obesity is the most frequently observed component of metabolic syndrome. The metabolic syndrome; clustering of abdominal obesity, dyslipidemia, hyperglycemia and hypertension, is a major public health challenge. The average prevalence of metabolic syndrome is 31%, and is associated with a two-fold increase in the risk of coronary heart disease, cerebrovascular disease, and a 1.5-fold increase in the risk of all-cause mortality.

  4. The early origins of obesity and insulin resistance: timing, programming and mechanisms.

    PubMed

    Nicholas, L M; Morrison, J L; Rattanatray, L; Zhang, S; Ozanne, S E; McMillen, I C

    2016-02-01

    Maternal obesity is associated with an increased risk of developing gestational diabetes mellitus and it also results in an increased risk of giving birth to a large baby with increased fat mass. Furthermore, it is also contributes to an increased risk of obesity and insulin resistance in the offspring in childhood, adolescence and adult life. It has been proposed that exposure to maternal obesity may therefore result in an 'intergenerational cycle' of obesity and insulin resistance. There is significant interest in whether exposure to maternal obesity around the time of conception alone contributes directly to poor metabolic outcomes in the offspring and whether dieting in the obese mother before pregnancy or around the time of conception has metabolic benefits for the offspring. This review focusses on experimental and clinical studies that have investigated the specific impact of exposure to maternal obesity during the periconceptional period alone or extending beyond conception on adipogenesis, lipogenesis and on insulin signalling pathways in the fat, liver and muscle of the offspring. Findings from these studies highlight the need for a better evidence base for the development of dietary interventions in obese women before pregnancy and around the time of conception to maximize the metabolic benefits and minimize the metabolic costs for the next generation.

  5. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity.

    PubMed

    Xiong, Xiao-Qing; Geng, Zhi; Zhou, Bing; Zhang, Feng; Han, Ying; Zhou, Ye-Bo; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2018-06-01

    Obesity-induced chronic inflammation is critical in the pathogenesis of insulin resistance, and the recruitment and proinflammatory activation of adipose tissue macrophages (ATMs) is important for the development of this process. Here, we examined the effects of fibronectin type III domain-containing 5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese mice. Male wild-type (WT) and FNDC5 -/- mice were fed with standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin resistance, macrophage accumulation and polarization and adipose tissue inflammation were determined in mice. Secondly, the macrophage polarity shift was further examined with flow cytometry in isolated stromal vascular fraction (SVF). Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced macrophage polarization, inflammation and the underlying signaling mechanism were investigated in RAW264.7 macrophages and primary mouse peritoneal cavity macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were examined in HFD-induced obese WT and FNDC5 -/- mice. FNDC5 gene deletion aggravated obesity, insulin resistance, fat accumulation and inflammation accompanied with enhanced AMPK inhibition, macrophages recruitment and M1 polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1 macrophage polarization and inflammatory cytokine production via AMPK phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and inflammatory cytokine production in adipose tissue of obese WT and FNDC5 -/- mice. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays several beneficial roles in obesity and may be used as a therapeutic regimen for preventing

  6. Dynapenic Abdominal Obesity Increases Mortality Risk among English and Brazilian Older Adults: A 10-Year Follow-Up of the ELSA and SABE Studies.

    PubMed

    da Silva Alexandre, T; Scholes, S; Ferreira Santos, J L; de Oliveira Duarte, Y A; de Oliveira, C

    2018-01-01

    There is little epidemiological evidence demonstrating that dynapenic abdominal obesity has higher mortality risk than dynapenia and abdominal obesity alone. Our main aim was to investigate whether dynapenia combined with abdominal obesity increases mortality risk among English and Brazilian older adults over ten-year follow-up. Cohort study. United Kingdom and Brazil. Data came from 4,683 individuals from the English Longitudinal Study of Ageing (ELSA) and 1,490 from the Brazilian Health, Well-being and Aging study (SABE), hence the final sample of this study was 6,173 older adults. The study population was categorized into the following groups: non-dynapenic/non-abdominal obese, abdominal obese, dynapenic, and dynapenic abdominal obese according to their handgrip strength (< 26 kg for men and < 16 kg for women) and waist circumference (> 102 cm for men and > 88 cm for women). The outcome was all-cause mortality over a ten-year follow-up. Adjusted hazard ratios by sociodemographic, behavioural and clinical characteristics were estimated using Cox proportional hazards models. The fully adjusted model showed that dynapenic abdominal obesity has a higher mortality risk among the groups. The hazard ratios (HR) were 1.37 for dynapenic abdominal obesity (95% CI = 1.12 - 1.68), 1.15 for abdominal obesity (95% CI = 0.98 - 1.35), and 1.23 for dynapenia (95% CI = 1.04 - 1.45). Dynapenia is an important risk factor for mortality but dynapenic abdominal obesity has the highest mortality risk among English and Brazilian older adults.

  7. Fatty and lean red meat consumption in China: differential association with Chinese abdominal obesity

    PubMed Central

    Wang, Z.; Zhang, B.; Zhai, F.; Wang, H.; Zhang, J.; Du, W.; Su, C.; Zhang, J.; Jiang, H.; Popkin, B. M.

    2014-01-01

    Aim We examined the longitudinal association between red meat (RM) consumption and the risk of abdominal obesity in Chinese adults. Methods and results Our data are from 16,822 adults aged 18 to 75 in the China Health and Nutrition Survey from 1993 to 2011. We assessed RM intake with three 24-hour dietary recalls. We defined abdominal obesity as a waist circumference (WC) ≥ 85 centimeters (cm) for men and ≥ 80 cm for women. Multilevel mixed-effect regression models showed that men experienced WC increases of 0.74 cm (95% confidence interval [CI]: 0.39–1.09) from a higher total intake of fresh RM and 0.59 cm (95% CI: 0.24–0. 95) from a higher intake of fatty fresh RM but 0.14 cm (95% CI: −0.39–0.66) from a higher intake of lean fresh RM in the top versus the bottom quartile when adjusted for potential confounders. In contrast, after additional adjustment for baseline WC, the odds ratios of abdominal obesity in men were attenuated for total fresh RM (1.25 [95% CI: 1.06–1.47]) and fatty fresh RM (1.22 [95% CI: 1.03–1.44]) but were still not affected by lean fresh RM (0.95 [95% CI: 0.75–1.22]). Women also showed a positive association of fatty fresh RM intake with abdominal obesity. Conclusion Greater intake of fatty fresh RM was significantly associated with higher WC (men only) and abdominal obesity risk in Chinese adults. The gender-specific differential association of fatty versus lean fresh RM warrants further study. PMID:24795160

  8. Fatty and lean red meat consumption in China: differential association with Chinese abdominal obesity.

    PubMed

    Wang, Z; Zhang, B; Zhai, F; Wang, H; Zhang, J; Du, W; Su, C; Zhang, J; Jiang, H; Popkin, B M

    2014-08-01

    We examined the longitudinal association between red meat (RM) consumption and the risk of abdominal obesity in Chinese adults. Our data are from 16,822 adults aged 18-75 in the China Health and Nutrition Survey from 1993 to 2011. We assessed RM intake with three 24-h dietary recalls. We defined abdominal obesity as a waist circumference (WC) ≥85 centimeters (cm) for men and ≥80 cm for women. Multilevel mixed-effect regression models showed that men experienced WC increases of 0.74 cm (95% confidence interval [CI]: 0.39-1.09) from a higher total intake of fresh RM and 0.59 cm (95% CI: 0.24-0. 95) from a higher intake of fatty fresh RM but 0.14 cm (95% CI: -0.39 to 0.66) from a higher intake of lean fresh RM in the top quartile versus non-consumers when adjusted for potential confounders. In contrast, after additional adjustment for baseline WC, the odds ratios of abdominal obesity in men were attenuated for total fresh RM (1.25 [95% CI: 1.06-1.47]) and fatty fresh RM (1.22 [95% CI: 1.03-1.44]) but were still not affected by lean fresh RM (0.95 [95% CI: 0.75-1.22]). Women also showed a positive association of fatty fresh RM intake with abdominal obesity. Greater intake of fatty fresh RM was significantly associated with higher WC (men only) and abdominal obesity risk in Chinese adults. The gender-specific differential association of fatty versus lean fresh RM warrants further study. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. The relationship between insulin resistance and endothelial dysfunction in obese adolescents.

    PubMed

    Brar, Preneet Cheema; Patel, Payal; Katz, Stuart

    2017-05-24

    Insulin resistance and endothelial dysfunction share a reciprocal relationship that links the metabolic and cardiovascular sequelae of obesity. We characterized the brachial artery reactivity testing (BART) and carotid artery-intima media thickness (CIMT) in adolescents categorized as obese insulin resistant (OIR) and obese not insulin resistant (ONIR). Lipoprotein particle (p) analysis and inflammatory cytokines in OIR and ONIR groups were also analyzed. Obese adolescents (n=40; mean body mass index [BMI] 35.6) were categorized as ONIR and OIR based on their homeostatic model assessment of insulin resistance (HOMA-IR) calculation (≤or> than 3.4). Ultrasound measured conduit arterial function BART, microvascular function (post-ischemic hyperemia) and conduit artery structure CIMT. BART did not differ according to IR status (mean±SD: 7.0±4.3% vs. 5.9±3.4% in ONIR and OIR, respectively, p=0.3, but post-ischemic hyperemia was significantly greater in the ONIR group (4.5±2.2 vs. 3.5±3, p=0.04). Atherogenic lipoprotein particles; large VLDL particles and small LDL particles were higher in the OIR compared to ONIR group. OIR adolescents demonstrate an inflamed atherogenic milieu compared to the ONIR adolescents. Microvascular function, but not conduit vessel structure or function, was impaired in association with IR.

  10. The combination of dynapenia and abdominal obesity as a risk factor for worse trajectories of IADL disability among older adults.

    PubMed

    Alexandre, Tiago da Silva; Scholes, Shaun; Ferreira Santos, Jair Licio; Duarte, Yeda Aparecida de Oliveira; de Oliveira, Cesar

    2017-10-02

    The concept of dynapenic obesity has been gaining great attention recently. However, there is little epidemiological evidence demonstrating that dynapenic abdominal obese individuals have worse trajectories of disability than those with dynapenia and abdominal obesity alone. Our aim was to investigate whether dynapenia combined with abdominal obesity can result in worse trajectories of instrumental activities of daily living (IADL) among English and Brazilian older adults over eight and ten years of follow-up, respectively. We used longitudinal data from 3374 participants from the English Longitudinal Study of Ageing (ELSA) and 1040 participants from the Brazilian Health, Well-being and Aging Study (SABE) who were free from disability as assessed by IADL at baseline. IADL disability was defined herein as a difficulty to perform the following: preparing meals, managing money, using transportation, shopping, using the telephone, house cleaning, washing clothes, and taking medications according to the Lawton IADL modified scale. The study population in each country was categorized into non-dynapenic/non-abdominal obese (reference group), abdominal obese, dynapenic and dynapenic abdominal obese according to their handgrip strength (<26 kg for men and <16 kg for women) and waist circumference (>102 cm for men and >88 cm for women). We used generalized linear mixed models with IADL as the outcome. The estimated change over time in IADL disability was significantly higher for participants with dynapenic abdominal obesity compared to those with neither condition in both cohorts (ELSA: +0.023, 95% CI = 0.012-0.034, p < 0.001; SABE: +0.065, 95% CI = 0.038-0.091, p < 0.001). Abdominal obesity was also associated with changes over time in IADL disability (ELSA: +0.009, 95% CI = 0.002-0.015, p < 0.05; SABE: +0.021, 95% CI = 0.002-0.041, p < 0.05), which was not observed for dynapenia. Abdominal obesity is an important risk factor for IADL decline but

  11. Bioactives in Blueberries Improve Insulin Sensitivity in Obese, Insulin-Resistant Men and Women1234

    PubMed Central

    Stull, April J.; Cash, Katherine C.; Johnson, William D.; Champagne, Catherine M.; Cefalu, William T.

    2010-01-01

    Dietary supplementation with whole blueberries in a preclinical study resulted in a reduction in glucose concentrations over time. We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women. A double-blinded, randomized, and placebo-controlled clinical study design was used. After screening to resolve study eligibility, baseline (wk 0) insulin sensitivity was measured on 32 obese, nondiabetic, and insulin-resistant subjects using a high-dose hyperinsulinemic-euglycemic clamp (insulin infusion of 120 mU(861 pmol)⋅m−2⋅min−1). Serum inflammatory biomarkers and adiposity were measured at baseline. At the end of the study, insulin sensitivity, inflammatory biomarkers, and adiposity were reassessed. Participants were randomized to consume either a smoothie containing 22.5 g blueberry bioactives (blueberry group, n = 15) or a smoothie of equal nutritional value without added blueberry bioactives (placebo group, n = 17) twice daily for 6 wk. Both groups were instructed to maintain their body weight by reducing ad libitum intake by an amount equal to the energy intake of the smoothies. Participants’ body weights were evaluated weekly and 3-d food records were collected at baseline, the middle, and end of the study. The mean change in insulin sensitivity improved more in the blueberry group (1.7 ± 0.5 mg⋅kg FFM−1⋅min−1) than in the placebo group (0.4 ± 0.4 mg⋅kg FFM−1⋅min−1) (P = 0.04). Insulin sensitivity was enhanced in the blueberry group at the end of the study without significant changes in adiposity, energy intake, and inflammatory biomarkers. In conclusion, daily dietary supplementation with bioactives from whole blueberries improved insulin sensitivity in obese, nondiabetic, and insulin-resistant participants. PMID:20724487

  12. Neural correlates of stress- and food cue-induced food craving in obesity: association with insulin levels.

    PubMed

    Jastreboff, Ania M; Sinha, Rajita; Lacadie, Cheryl; Small, Dana M; Sherwin, Robert S; Potenza, Marc N

    2013-02-01

    Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR. Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI. Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus. These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity.

  13. Gestational diabetes predicts the risk of childhood overweight and abdominal circumference independent of maternal obesity.

    PubMed

    Nehring, I; Chmitorz, A; Reulen, H; von Kries, R; Ensenauer, R

    2013-12-01

    Gestational diabetes mellitus is believed to be a risk factor for childhood overweight/obesity. We aimed to assess whether this association is either a reflection or independent of confounding by maternal BMI. Data from 7355 mother-child dyads of the German Perinatal Prevention of Obesity cohort with full anthropometric information on mothers and children, gestational diabetes and confounding factors were obtained at school entry health examination. We calculated crude and adjusted logistic regression models for the association of gestational diabetes and childhood overweight/obesity and abdominal adiposity defined by age- and sex-specific percentiles for BMI and waist circumference. Among all children (mean age 5.8 years), 8.1% were overweight, 2.6% were obese and 15.5% had abdominal adiposity. The prevalence of overweight (obesity) was 21% (8.2%) in children of mothers with gestational diabetes and 10.4% (2.4%) in children of healthy mothers. Analyses with adjustment for maternal BMI and other potential confounders yielded an odds ratio of 1.81 (95% CI 1.23-2.65) and 2.80 (95% CI 1.58-4.99) for the impact of gestational diabetes on childhood overweight and obesity, respectively. Similar results were obtained for the risk of childhood abdominal adiposity (odds ratio 1.64, 95% CI 1.16-2.33) by maternal gestational diabetes. The postulated increased risk of overweight and abdominal adiposity in offspring of mothers with gestational diabetes cannot be explained by maternal BMI alone and may be stronger for childhood obesity than for overweight. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  14. Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis

    PubMed Central

    Murray, Kevin J.; Rendahl, Aaron K.; Geor, Raymond J.; Schultz, Nichol E.; McCue, Molly E.

    2018-01-01

    Background Metabolomics, the study of small‐molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS). Objectives (1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis. Animals Twenty Welsh Ponies (mean ± SD; 13.8 ± 9.0 years) classified as non‐insulin dysregulated [CON] (n = 10, insulin < 30 mU/L) or insulin dysregulated [ID] (n = 10, insulin > 60 mU/L) at 75 minutes after administration of Karo syrup, obese (n = 6) or nonobese (n = 14), and history of laminitis (n = 9) or no history of laminitis (n = 11). Methods Case‐control study. Metabolomic analysis was performed on serum obtained at 0 minutes (baseline) and 75 minutes during the OST. Data were analyzed with multivariable mixed linear models with significance set at P ≤ .05. Results Metabolomic analysis of 646 metabolites (506 known) detected significant metabolite differences. At baseline, 55 metabolites (insulin response), 91 metabolites (obesity status), and 136 metabolites (laminitis history) were different. At 75 minutes, 51 metabolites (insulin response), 102 metabolites (obesity status), and 124 metabolites (laminitis history) were different. Conclusions and Clinical Importance Use of metabolomics could have diagnostic utility for early detection of EMS and provide new knowledge regarding the pathophysiology of metabolic perturbations associated with this condition that might lead to improved clinical management. PMID:29572947

  15. Association between general and abdominal obesity with high blood pressure: difference between genders.

    PubMed

    Silva, Alison O; Silva, Micaelly V; Pereira, Lisley K N; Feitosa, Wallacy M N; Ritti-Dias, Raphael M; Diniz, Paula R B; Oliveira, Luciano M F T

    2016-01-01

    To assess the association between general and abdominal obesity with high blood pressure in adolescents of both genders from the public school system. This was an epidemiological, descriptive, exploratory study, with a quantitative approach and local scope whose sample consisted of 481 high school students (aged 14-19), selected by using a random cluster sampling strategy. Blood pressure was measured through the use of automated monitor and was considered high when the pressure values were at or above the 95th percentile. The analyses were performed using the chi-squared test and binary logistic regression. The prevalence of high blood pressure was 6.4%, and it was higher among boys (9.0% vs. 4.7%, p<0.05). There was no significant difference between general (p=0.903) and abdominal obesity (p=0.157) when genders were compared. After adjusting for age, high blood pressure was associated with general (OR=6.4; p<0.001) and abdominal obesity (OR=7.0; p<0.001) only among boys, when comparing the fourth quartile with the first quartile of body mass index (≤ 18.6 kg/m(2)vs. ≥ 23.5 kg/m(2)) and waist circumference (≤ 69 cm vs. ≥ 80.1cm). It was observed that general and abdominal obesity are associated with high blood pressure only in boys, regardless of age. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  16. Distribution of abdominal adiposity and cardiovascular risk factors in yaquis indians from sonora, méxico.

    PubMed

    Brito-Zurita, Olga; Domínguez-Banda, Alberto; Ugalde-Aguirre, Víctor; Cortez-Valenzuela, Ana; Villanueva-Pérez, Rosa; Rodríguez-Morán, Martha; Guerrero-Romero, Fernando

    2007-12-01

    Studies on adiposity in indigenous populations from Mexico are scarce and there are not previous reports that examine the topography of abdominal fat depot and cardiovascular risk factors. Therefore, we determined the distribution of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and analyzed its relationship with cardiovascular risk factors, in Yaqui Indians. In a cross-sectional population based study, a total of 82 apparently healthy Yaqui Indians (age 44 +/- 14 years and BMI 27.9 +/- 4.2 kg/m(2)) were randomly enrolled from Vicam, Bacum, and Potam, traditional Yaqui communities from Sonora, in northwest Mexico. Anthropometric parameters, single-slice computed tomography scans at the L(2)-L(3) intervertebral space, fasting glucose, insulin, and lipid profile were assessed. A total of 49 (59.7%) individuals were obese, showing a predominant area of abdominal SAT (319.5 +/- 118.2 cm(2)) over abdominal VAT (134.6 +/- 58.4 cm(2)). Both abdominal VAT (r = 0.54, P = .001; and r = 0.36, P = .01) and SAT (r = 0.15, P = .001; r = 0.47, P = .01) were positively correlated with age and BMI. Abdominal VAT was positively correlated with insulin (r = 0.69, P = .0001) and triglycerides levels (r = 0.42, P = .01). Among Yaquis Indians, obesity with predominant abdominal SAT is common and hyperinsulinemia is the most frequent cardiovascular risk factor. Abdominal VAT, but not abdominal SAT, was related to hyperinsulinemia and hypertriglyceridemia.

  17. Tumor Progression Locus 2 (TPL2) Regulates Obesity-Associated Inflammation and Insulin Resistance

    PubMed Central

    Perfield, James W.; Lee, Yunkyoung; Shulman, Gerald I.; Samuel, Varman T.; Jurczak, Michael J.; Chang, Eugene; Xie, Chen; Tsichlis, Phillip N.; Obin, Martin S.; Greenberg, Andrew S.

    2011-01-01

    OBJECTIVE Obesity-associated low-grade systemic inflammation resulting from increased adipose mass is strongly related to the development of insulin resistance and type 2 diabetes as well as other metabolic complications. Recent studies have demonstrated that the obese metabolic state can be improved by ablating certain inflammatory signaling pathways. Tumor progression locus 2 (TPL2), a kinase that integrates signals from Toll receptors, cytokine receptors, and inhibitor of κ-B kinase-β is an important regulator of inflammatory pathways. We used TPL2 knockout (KO) mice to investigate the role of TPL2 in mediating obesity-associated inflammation and insulin resistance. RESEARCH DESIGN AND METHODS Male TPL2KO and wild-type (WT) littermates were fed a low-fat diet or a high-fat diet to investigate the effect of TPL2 deletion on obesity, inflammation, and insulin sensitivity. RESULTS We demonstrate that TPL2 deletion does not alter body weight gain or adipose depot weight. However, hyperinsulinemic euglycemic clamp studies revealed improved insulin sensitivity with enhanced glucose uptake in skeletal muscle and increased suppression of hepatic glucose output in obese TPL2KO mice compared with obese WT mice. Consistent with an improved metabolic phenotype, immune cell infiltration and inflammation was attenuated in the adipose tissue of obese TPL2KO mice coincident with reduced hepatic inflammatory gene expression and lipid accumulation. CONCLUSIONS Our results provide the first in vivo demonstration that TPL2 ablation attenuates obesity-associated metabolic dysfunction. These data suggest TPL2 is a novel target for improving the metabolic state associated with obesity. PMID:21346175

  18. Physical activity in adolescence and abdominal obesity in adulthood: a case-control study among women shift workers.

    PubMed

    Garcez, Anderson da Silva; Olinto, Maria Teresa Anselmo; Canuto, Raquel; Olinto, Beatriz Anselmo; Pattussi, Marcos Pascoal; Paniz, Vera Maria Vieira

    2015-01-01

    Physical activity may have a protective effect against abdominal obesity, an important risk factor for cardiometabolic diseases. Thus, the aim of this study was to examine the association between the practice of physical activities in adolescence and abdominal obesity in adulthood among women shift workers in Southern Brazil in 2011. This case-control study included 215 cases (waist circumference greater than or equal to 88 cm) and 326 controls. For both the case and control groups, participation in leisure-time physical activities was most frequent in adolescence and was significantly less in adulthood. After adjusting for potential confounding factors, women who participated in five or more physical activities in adolescence were 50 percent less likely to have abdominal obesity than women who participated in one activity or no physical activities (Odds Ratio = 0.50; 95% confidential interval: 0.27-0.93, p value = .029). Participation in various types of leisure-time physical activities in adolescence may protect against abdominal obesity in adulthood, even if the number of physical activities decreases over time. This finding demonstrated the importance of physical activity as well as the period of life in which these should be encouraged for the prevention of health disorders, such as abdominal obesity.

  19. Correlation of P-wave dispersion with insulin sensitivity in obese adolescents.

    PubMed

    Sert, Ahmet; Aslan, Eyup; Buyukınan, Muammer; Pirgon, Ozgur

    2017-03-01

    P-wave dispersion is a new and simple electrocardiographic marker that has been reported to be associated with inhomogeneous and discontinuous propagation of sinus impulses. In the present study, we evaluated P-wave dispersion in obese adolescents and investigated the relationship between P-wave dispersion, cardiovascular risk factors, and echocardiographic parameters. We carried out a case-control study comparing 150 obese adolescents and 50 healthy controls. Maximum and minimum P-wave durations were measured using a 12-lead surface electrocardiogram, and P-wave dispersion was calculated as the difference between these two measures. Echocardiographic examination was also performed for each subject. Multivariate linear regression analysis with stepwise variable selection was used to evaluate parameters associated with increased P-wave dispersion in obese subjects. Maximum P-wave duration and P-wave dispersion were significantly higher in obese adolescents than control subjects (143±19 ms versus 117±20 ms and 49±15 ms versus 29±9 ms, p<0.0001 for both). P-wave dispersion was positively correlated with body mass index, waist and hip circumferences, systolic and diastolic blood pressures, total cholesterol, serum levels of low-density lipoprotein cholesterol, triglycerides, glucose, and insulin, homoeostasis model assessment for insulin resistance score, left ventricular mass, and left atrial dimension. P-wave dispersion was negatively correlated with high-density lipoprotein cholesterol levels. By multiple stepwise regression analysis, left atrial dimension (β: 0.252, p=0.008) and homoeostasis model assessment for insulin resistance (β: 0.205; p=0.009) were independently associated with increased P-wave dispersion in obese adolescents. Insulin resistance is a significant, independent predictor of P-wave dispersion in obese adolescents.

  20. [The role of uric acid in the insulin resistance in children and adolescents with obesity].

    PubMed

    de Miranda, Josiane Aparecida; Almeida, Guilherme Gomide; Martins, Raissa Isabelle Leão; Cunha, Mariana Botrel; Belo, Vanessa Almeida; dos Santos, José Eduardo Tanus; Mourão-Júnior, Carlos Alberto; Lanna, Carla Márcia Moreira

    2015-12-01

    To investigate the association between serum uric acid levels and insulin resistance in children and adolescents with obesity. Cross-sectional study with 245 children and adolescents (134 obese and 111 controls), aged 8 to 18 years. The anthropometric variables (weight, height and waist circumference), blood pressure and biochemical parameters were collected. The clinical characteristics of the groups were analyzed by t-test or chi-square test. To evaluate the association between uric acid levels and insulin resistance the Pearson's test and logistic regression were applied. The prevalence of insulin resistance was 26.9%. The anthropometric variables, systolic and diastolic blood pressure and biochemical variables were significantly higher in the obese group (p<0.001), except for the high-density-lipoprotein cholesterol. There was a positive and significant correlation between anthropometric variables and uric acid with HOMA-IR in the obese and in the control groups, which was higher in the obese group and in the total sample. The logistic regression model that included age, gender and obesity, showed an odds ratio of uric acid as a variable associated with insulin resistance of 1.91 (95%CI 1.40 to 2.62; p<-0.001). The increase in serum uric acid showed a positive statistical correlation with insulin resistance and it is associated with and increased risk of insulin resistance in obese children and adolescents. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  1. Defective calcium inactivation causes long QT in obese insulin-resistant rat.

    PubMed

    Lin, Yen-Chang; Huang, Jianying; Kan, Hong; Castranova, Vincent; Frisbee, Jefferson C; Yu, Han-Gang

    2012-02-15

    The majority of diabetic patients who are overweight or obese die of heart disease. We suspect that the obesity-induced insulin resistance may lead to abnormal cardiac electrophysiology. We tested this hypothesis by studying an obese insulin-resistant rat model, the obese Zucker rat (OZR). Compared with the age-matched control, lean Zucker rat (LZR), OZR of 16-17 wk old exhibited an increase in QTc interval, action potential duration, and cell capacitance. Furthermore, the L-type calcium current (I(CaL)) in OZR exhibited defective inactivation and lost the complete inactivation back to the closed state, leading to increased Ca(2+) influx. The current density of I(CaL) was reduced in OZR, whereas the threshold activation and the current-voltage relationship of I(CaL) were not significantly altered. L-type Ba(2+) current (I(BaL)) in OZR also exhibited defective inactivation, and steady-state inactivation was not significantly altered. However, the current-voltage relationship and activation threshold of I(BaL) in OZR exhibited a depolarized shift compared with LZR. The total and membrane protein expression levels of Cav1.2 [pore-forming subunit of L-type calcium channels (LTCC)], but not the insulin receptors, were decreased in OZR. The insulin receptor was found to be associated with the Cav1.2, which was weakened in OZR. The total protein expression of calmodulin was reduced, but that of Cavβ2 subunit was not altered in OZR. Together, these results suggested that the 16- to 17-wk-old OZR has 1) developed cardiac hypertrophy, 2) exhibited altered electrophysiology manifested by the prolonged QTc interval, 3) increased duration of action potential in isolated ventricular myocytes, 4) defective inactivation of I(CaL) and I(BaL), 5) weakened the association of LTCC with the insulin receptor, and 6) decreased protein expression of Cav1.2 and calmodulin. These results also provided mechanistic insights into a remodeled cardiac electrophysiology under the condition of

  2. Abdominal Pain After Roux-En-Y Gastric Bypass for Morbid Obesity.

    PubMed

    Mala, Tom; Høgestøl, Ingvild

    2018-05-01

    Roux-en-Y gastric bypass is widely used as treatment of morbid obesity. Weight loss, effects on obesity-related co-morbidities and quality of life are well documented post Roux-en-Y gastric bypass. Other outcome measures are less well studied. This review explores aspects of prevalence, diagnostic evaluations, etiology, and treatment of abdominal pain specific to Roux-en-Y gastric bypass. The review is based on PubMed searches and clinical experience with Roux-en-Y gastric bypass. Symptoms in the early postoperative phase (<30 days) were not included. Based on limited evidence, up to about 30% of the patients may perceive recurrent abdominal pain post Roux-en-Y gastric bypass in the long term. A substantial subset of patients will need health-care evaluation for acute abdominal pain and hospital admission. The etiology of abdominal pain is heterogeneous and includes gallstone-related disease, intestinal obstruction, anastomotic ulcerations and strictures, intestinal dysmotility, dysfunctional eating, and food intolerance. Surgical treatment and guidance on diet and eating habits may allow symptom relief. The cause of pain remains undefined for a subset of patients. Impact of abdominal pain post Roux-en-Y gastric bypass on the perception of well-being, quality of life, and patient satisfaction with the procedure needs to be further evaluated and may be influenced by complex interactions between new symptoms post Roux-en-Y gastric bypass and relief of pre-existing symptoms. Abdominal pain should be part of follow-up consultations post Roux-en-Y gastric bypass. Future studies should focus on combined evaluations before and after surgery to enlighten potential casual relationships between abdominal pain and Roux-en-Y gastric bypass.

  3. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.

    PubMed

    Vandanmagsar, Bolormaa; Youm, Yun-Hee; Ravussin, Anthony; Galgani, Jose E; Stadler, Krisztian; Mynatt, Randall L; Ravussin, Eric; Stephens, Jacqueline M; Dixit, Vishwa Deep

    2011-02-01

    The emergence of chronic inflammation during obesity in the absence of overt infection or well-defined autoimmune processes is a puzzling phenomenon. The Nod-like receptor (NLR) family of innate immune cell sensors, such as the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (Nlrp3, but also known as Nalp3 or cryopyrin) inflammasome are implicated in recognizing certain nonmicrobial originated 'danger signals' leading to caspase-1 activation and subsequent interleukin-1β (IL-1β) and IL-18 secretion. We show that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity. We further found that the Nlrp3 inflammasome senses lipotoxicity-associated increases in intracellular ceramide to induce caspase-1 cleavage in macrophages and adipose tissue. Ablation of Nlrp3 in mice prevents obesity-induced inflammasome activation in fat depots and liver as well as enhances insulin signaling. Furthermore, elimination of Nlrp3 in obese mice reduces IL-18 and adipose tissue interferon-γ (IFN-γ) expression, increases naive T cell numbers and reduces effector T cell numbers in adipose tissue. Collectively, these data establish that the Nlrp3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.

  4. Obesity, Insulin Resistance and Diabetes: Sex Differences and Role of Estrogen Receptors

    PubMed Central

    Meyer, Matthias R.; Clegg, Deborah J.; Prossnitz, Eric R.; Barton, Matthias

    2010-01-01

    Obesity increases the risk of coronary artery disease through insulin resistance, diabetes, arterial hypertension, and dyslipidemia. The prevalence of obesity has increased worldwide and is particularly high among middle-aged women and men. After menopause, women are at an increased risk to develop visceral obesity due to the loss of endogenous ovarian hormone production. Effects of estrogens are classically mediated by the two nuclear estrogen receptors (ERs) α and β. In addition, more recent research has shown that the intracellular transmembrane G protein-coupled estrogen receptor, GPER, originally designated as GPR30, also mediates some of the actions attributed to estrogens. Estrogen and its receptors are important regulators of body weight and insulin sensitivity not only in women, but also in men as demonstrated by ER mutations in rodents and humans. This article reviews the role of sex hormones and estrogen receptors in the context of obesity, insulin sensitivity and diabetes as well as the related clinical issues in females and males. PMID:21281456

  5. Methods for quantifying adipose tissue insulin resistance in overweight/obese humans.

    PubMed

    Ter Horst, K W; van Galen, K A; Gilijamse, P W; Hartstra, A V; de Groot, P F; van der Valk, F M; Ackermans, M T; Nieuwdorp, M; Romijn, J A; Serlie, M J

    2017-08-01

    Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies. We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of [1,1,2,3,3- 2 H 5 ]glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m -2 ). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method. Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, P<0.001), (2) suppression of plasma non-esterified fatty acid (NEFA) concentrations (r=0.899, P<0.001), (3) the Adipose tissue Insulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, P<0.001), (4) the fasting plasma insulin-glycerol product (r=-0.467, P<0.001), (5) the Adipose Tissue Insulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, P<0.001), (6) the Quantitative Insulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, P<0.001), and (7) the QUICKI-glycerol index (r=0.671, P<0.001). Bland-Altman plots showed no systematic errors for the suppression indices but proportional errors for all fasting indices. Receiver-operator characteristic curves confirmed that all indices were able to detect adipose tissue insulin resistance (area

  6. Insulin and Leptin Relations in Obesity: A Multimedia Approach

    ERIC Educational Resources Information Center

    Yokaichiya, Daniela K.; Galembeck, Eduardo; Torres, Bayardo B.; Da Silva, Jose Antonio; de Araujo, Daniele R.

    2008-01-01

    Obesity has been recognized as a worldwide public health problem. It significantly increases the chances of developing several diseases, including Type II diabetes. The roles of insulin and leptin in obesity involve reactions that can be better understood when they are presented step by step. The aim of this work was to design software with data…

  7. Prevalence of General Obesity and Abdominal Obesity in the Spanish Adult Population (Aged 25-64 Years) 2014-2015: The ENPE Study.

    PubMed

    Aranceta-Bartrina, Javier; Pérez-Rodrigo, Carmen; Alberdi-Aresti, Goiuri; Ramos-Carrera, Natalia; Lázaro-Masedo, Sonia

    2016-06-01

    According to the 2013 analysis of the Institute of Health Metrics, high body mass index values are the most important risk factor for disease in Spain. Consequently, we describe the prevalence of total obesity and abdominal obesity in the Spanish adult population (25-64 years) for 2014-2015. The sample was taken from the ENPE study, a cross-sectional study with a representative sample of the noninstitutionalized population (n = 6800) carried out between May 2014 and May 2015. This analysis refers to the population between age 25 and 64 years (n = 3966). The anthropometric measurements were performed by trained observers at participants' homes according to standard international protocols. Body mass index ≥ 25 was defined as overweight and ≥ 30 as obesity. Abdominal obesity was classified as waist > 102 cm in men and > 88 cm in women. The estimated prevalence of overweight in the Spanish adult population (25-64 years) was 39.3% 95% confidence interval [95%CI], 35.7%-42.9%). The prevalence of general obesity was 21.6% (95%CI, 19.0%-24.2%) and, more specifically, was 22.8% (95%CI, 20.6%-25.0%) among men and 20.5% (95%CI, 18.5%-22.5%) among women, and rose with age. The prevalence of abdominal obesity was estimated at 33.4% (95%CI, 31.1%-35.7%) and was higher among women (43.3%; 95%CI, 41.1%-45.8%) than among men (23.3%; 95%CI, 20.9%-25.5%), and also rose with age. The prevalence of general obesity and abdominal obesity in Spain is high, although the distribution differs according to autonomous community. A comparison with earlier data reveals a considerable increase in overweight, indicating the need for routine monitoring and comprehensive initiatives. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  8. Vitamin D deficiency and insulin resistance as risk factors for dyslipidemia in obese children.

    PubMed

    Erol, Meltem; Bostan Gayret, Özlem; Hamilçıkan, Şahin; Can, Emrah; Yiğit, Özgu L

    2017-04-01

    Dyslipidemia is one of the major complications of obesity; vitamin D deficiency and insulin resistance are attending metabolic complications in dyslipidemic obese children. Objective. To determine if vitamin D deficiency and insulin resistance are risk factors for dyslipidemia in obese children. This study was conducted in the Department of Pediatrics at Bagcilar Training and Research Hospital in Istanbul, Turkey between 2014 and 2015. Obese patients whose age range was 8-14 were included in the study. The serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, highdensity lipoprotein cholesterol, fasting glucose, insulin, alanine aminotransferase, vitamin D levels were measured; a liver ultrasonography was performed. Homeostatic model assessment (HOMA-IR), was used to calculate insulin resistance. 108 obese children were included; 39 (36.11%) had dyslipidemia. The average fasting blood glucose (88.74 ± 7.58 vs. 95.31 ± 6.82; p= 0.0001), insulin level (14.71 ± 12.44 vs. 24.39 ± 15.02; p= 0.0001) and alanine aminotransferase level (23.45 ± 11.18 vs. 30.4 ± 18.95; p= 0.018) were significantly higher in the children with dyslipidemia. In the dyslipidemic obese children, the average hepatosteatosis rate and HOMA-IR level were higher; 28 (71.9%) had hepatosteatosis, 37 (94.87%) had insulin resistance; the vitamin D levels were <20 ng/ml in 69.3%. Vitamin D deficiency was significantly more common (p= 0.033). The multivariate regression analysis confirmed that the increase in the HOMA-IR level (p= 0.015) and the low vitamin D level (p= 0.04) were important risk factors for dyslipidemia. Obese children in our region exhibit low vitamin D and increased HOMA-IR levels, which are efficient risk factors of dyslipidemia.

  9. Obesity, insulin resistance and comorbidities – Mechanisms of association

    PubMed Central

    Castro, Ana Valeria B.; Kolka, Cathryn M.; Kim, Stella P.; Bergman, Richard N.

    2015-01-01

    Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. PMID:25211442

  10. Comprehensive assessment of insulin resistance in non-obese Asian Indian and Chinese men.

    PubMed

    Tan, Hong Chang; Yew, Tong Wei; Chacko, Shaji; Tai, E Shyong; Kovalik, Jean-Paul; Ching, Jianhong; Myo Thant, Sandi; Khoo, Chin Meng

    2018-03-27

    Indian individuals are more insulin resistant (IR) than Chinese individuals, even among those with a non-obese body mass index (BMI). However, BMI often underestimates body fat in Indian individuals, and it remains unclear whether Indians would remain more IR than Chinese individuals when both BMI and body fat are equally matched. Using the hyperinsulinemic-euglycemic clamp with stable-isotope infusion, we comprehensively assessed IR between 13 non-obese Indian men with 13 Chinese men matched for age, BMI and body fat. We further compared the differences in insulin metabolic clearance rate (MCR) between the two groups and its relationship with various metabolic parameters. The response of lipid and amino acid metabolism to insulin stimulation was also evaluated using metabolomic profiling. The rates of endogenous glucose production during fasting were similar, and endogenous glucose production was completely suppressed during insulin clamp for both ethnic groups. Glucose disappearance during insulin clamp was also similar between the two groups, even after accounting for differences in insulin concentration. Metabolomic profiles of amino acids and various acylcarnitines were similar during both fasting and insulin clamp. However, plasma insulin during clamp was significantly higher in Indian men, indicating that insulin MCR was lower. Insulin MCR correlated significantly with total adiposity and skeletal muscle insulin sensitivity. When equally matched for body fat, non-obese Indian men had similar skeletal muscle insulin sensitivity and endogenous glucose production to Chinese men. The effects of insulin on lipid and amino acid metabolism were also similar. Low insulin MCR is associated with greater adiposity and lower skeletal muscle insulin sensitivity. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  11. Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance.

    PubMed

    Nandipati, Kalyana C; Subramanian, Saravanan; Agrawal, Devendra K

    2017-02-01

    Obesity-induced low-grade inflammation (metaflammation) impairs insulin receptor signaling. This has been implicated in the development of insulin resistance. Insulin signaling in the target tissues is mediated by stress kinases such as p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, inhibitor of NF-kB kinase complex β (IKKβ), AMP-activated protein kinase, protein kinase C, Rho-associated coiled-coil containing protein kinase, and RNA-activated protein kinase. Most of these kinases phosphorylate several key regulators in glucose homeostasis. The phosphorylation of serine residues in the insulin receptor and IRS-1 molecule results in diminished enzymatic activity in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This has been one of the key mechanisms observed in the tissues that are implicated in insulin resistance especially in type 2 diabetes mellitus (T2-DM). Identifying the specific protein kinases involved in obesity-induced chronic inflammation may help in developing the targeted drug therapies to minimize the insulin resistance. This review is focused on the protein kinases involved in the inflammatory cascade and molecular mechanisms and their downstream targets with special reference to obesity-induced T2-DM.

  12. Glucose alteration and insulin resistance in asymptomatic obese children and adolescents.

    PubMed

    Assunção, Silvana Neves Ferraz de; Boa Sorte, Ney Christian Amaral; Alves, Crésio de Aragão Dantas; Mendes, Patricia S Almeida; Alves, Carlos Roberto Brites; Silva, Luciana Rodrigues

    Obesity is associated with the abnormal glucose metabolism preceding type 2 diabetes mellitus. Thus, further investigation on the prediction of this lethal outcome must be sought. The objective was the profile glycemic assessment of asymptomatic obese children and adolescents from Salvador, Brazil. A fasting venous blood sample was obtained from 90 consecutive obese individuals aged 8-18 years, of both sexes, for laboratory determinations of glycated hemoglobin, basal insulin, and the Homeostasis Model Assessment Insulin Resistance index. The clinical evaluation included weight, height, waist circumference, assessment of pubertal development, and acanthosis nigricans research. The body mass index/age indicator was used for the severity of overweight assessment. Glycemic alterations were evidenced clinically and biochemically, although these individuals had no complaints or symptoms related to blood sugar levels. Quantitative and qualitative variables were respectively expressed measures of central tendency/dispersion and simple/relative frequency, using the SPSS, version 20.0. A p-value <0.05 was considered significant. Notably, this study found a high prevalence of glucose and insulin disorders in asymptomatic obese children and adolescents. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  13. Regional Differences in Adipose Tissue Hormone/Cytokine Production Before and After Weight Loss in Abdominally Obese Women

    PubMed Central

    You, Tongjian; Wang, Xuewen; Murphy, Karin M.; Lyles, Mary F.; Demons, Jamehl L.; Yang, Rongze; Gong, Da-Wei; Nicklas, Barbara J.

    2014-01-01

    Objective To compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss. Design and Methods Forty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: ~2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention. Results Adipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined. The intervention resulted in significant weight loss (−10.1 ±0.7 kg, P<0.001). At baseline, gene expression of adiponectin were higher (P<0.01), and gene expression and release of IL-6 were lower (both P<0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P<0.05 to P<0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P<0.05). Conclusion A 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity. PMID:24634403

  14. Effect of android to gynoid fat ratio on insulin resistance in obese youth.

    PubMed

    Aucouturier, Julien; Meyer, Martine; Thivel, David; Taillardat, Michel; Duché, Pascale

    2009-09-01

    Upper body fat distribution is associated with the early development of insulin resistance in obese children and adolescents. To determine if an android to gynoid fat ratio is associated with the severity of insulin resistance in obese children and adolescents, whereas peripheral subcutaneous fat may have a protective effect against insulin resistance. The pediatric department of University Hospital, Clermont-Ferrand, France. A retrospective analysis using data from medical consultations between January 2005 and January 2007. Data from 66 obese children and adolescents coming to the hospital for medical consultation were used in this study. Subjects were stratified into tertiles of android to gynoid fat ratio determined by dual-energy x-ray absorptiometry. Insulin resistance was assessed by the homeostasis model of insulin resistance (HOMA-IR) index. There were no differences in weight, body mass index, and body fat percentage between tertiles. Values of HOMA-IR were significantly increased in the 2 higher tertiles (mean [SD], tertile 2, 2.73 [1.41]; tertile 3, 2.89 [1.28]) compared with the lower tertile (tertile 1, 1.67 [1.24]) of android to gynoid fat ratio (P < .001). The HOMA-IR value was significantly associated with android to gynoid fat ratio (r = 0.35; P < .01). Android fat distribution is associated with an increased insulin resistance in obese children and adolescents. An android to gynoid fat ratio based on dual-energy x-ray absorptiometry measurements is a useful and simple technique to assess distribution of body fat associated with an increased risk of insulin resistance.

  15. Prevalence of obesity and abdominal obesity from four to 16 years old children living in the Mexico-USA border.

    PubMed

    Bacardí-Gascón, Montserrat; Jones, Elizabeth G; Jiménez-Cruz, Arturo

    2013-01-01

    The prevalence of obesity among Mexicans is alarming in both the child and adult populations. The objective of this study was to determine the levels of overweight, obesity and abdominal obesity in pre-school (PS), elementary (ES), and middle high (MHS) public school children from Tijuana. From February to April of 2011, a bietapic random sample was selected by cluster method of 30 PS, 30 ES, and 30 MHS children. And a sample of 30 groups for each level was chosen. Twenty elementary teachers and eight graduate students were trained at one central location on how to take anthropometric measurements using a portable scale, a stadiometer, and a measuring tape to determine weight, height, and waist circumference. Body Mass Index values were computed and compared to age/gender BMI percentiles according to WHO criteria. Waist circumference for-age at the 90th percentile from NHANES III (Mexican-American) was used to define abdominal obesity. The sample was composed of 646 PS children, 961 ES children, and 1,095 MHS children. Their ages ranged from 4- 16 years. Results showed an overall prevalence of overweight and obesity in younger than 5y preschool children (> 2 SD) of 23.1%, in ≥ 5 y PS (> 1 SD) of 33.8%, in ES children of 46.3%, and in MHS children of 41.9%. Abdominal obesity in PS children was 18%, in ES children was 16.7%, and in MHS children was 15.2%. These results warrant immediate and comprehensive actions to prevent a critical public health problem in Mexico. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  16. Abdominal obesity and its association with health-related quality of life in adults: a population-based study in five Chinese cities

    PubMed Central

    2014-01-01

    Background This study aimed to investigate the prevalence of abdominal obesity and its association with the health-related quality of life (HRQOL) in a randomly selected Chinese sample. Methods A population-based sample of 3,600 residents aged 18–80 years was selected randomly from 5 Chinese cities. Demographic information, and waist and hip circumference measurements were obtained. The Mandarin version of the Short Form 36 Health Survey questionnaire (SF-36) was used to assess the HRQOL. Waist circumference (WC) and waist-to-hip ratio (WHR) were used as measures of abdominal obesity, and the prevalence of abdominal obesity and its association with HRQOL were analysed. Results Among the 3,184 participants included in the analysis, the prevalence of abdominal obesity was about 45% in both women and men as evaluated by WC, and about 40% in women and 33% in men as evaluated by WHR. The prevalence varied by city, region, age, marital status, education level, family income, smoking, and the presence of chronic diseases. Both WC and WHR increased with age, and men had larger WC and WHR than women in most age groups. In women, abdominal obesity, as determined by both WC and WHR, was associated with meaningful impairments in 4 physical health scales and 2 mental health scales. In men, abdominal obesity, as determined by WC, was associated with 1 physical health scale and 1 mental health scale, and it was associated with 2 physical health scales based on WHR. Conclusions Physical health, but not mental health, was more vulnerable to impairment with abdominal obesity, and the impairments varied between genders. Public health agencies should emphasize that abdominal obesity impairs physical health. PMID:24925310

  17. Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats☆

    PubMed Central

    Castro, Gisele; C. Areias, Maria Fernanda; Weissmann, Lais; Quaresma, Paula G.F.; Katashima, Carlos K.; Saad, Mario J.A.; Prada, Patricia O.

    2013-01-01

    Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala. PMID:24251109

  18. Visceral obesity, impaired glucose tolerance, metabolic syndrome, and growth hormone therapy.

    PubMed

    Attallah, Hamdee; Friedlander, Anne L; Hoffman, Andrew R

    2006-07-01

    Overweight adults with impaired glucose tolerance have a 5-10% risk of developing diabetes per year, and insulin resistance is an important cause of progression to diabetes in these individuals. Weight loss has been shown to improve insulin sensitivity and prevent or delay progression to diabetes. According to recent studies, the improvement in insulin sensitivity that occurs with weight loss is closely linked to the reduction of visceral adipose tissue (VAT), the collection of intra-abdominal adipose depots that includes omental and intrahepatic fat. After controlling for BMI, whole body fat, and subcutaneous fat, only VAT is an independent predictor of endogenous insulin sensitivity and glucose tolerance before or after weight loss. This, in turn, suggests that reducing VAT is crucial to improving insulin sensitivity and preventing diabetes in high-risk individuals. Recombinant human growth hormone (GH) is a lipolytic drug that reduces total body, abdominal, and visceral fat in growth hormone-deficient (GHD) adults. Several studies have reported substantial reductions in VAT following GH treatment in this population. Like GHD adults, abdominally obese individuals have increased VAT, insulin resistance, and growth hormone levels that are below normal during continuous 24-h monitoring. These similarities have prompted a number of recent investigations in abdominally obese adults that reported significant reductions in truncal and visceral fat and an improvement in insulin sensitivity following prolonged GH administration. However, other studies have shown that insulin resistance and glucose concentrations transiently worsen during the first few weeks of GH treatment and that these deleterious effects can persist even after VAT reduction has occurred. Prior studies involving GH treatment were generally limited to adults who were normoglycemic at baseline. Less is known about the effects of GH in adults with impaired glucose tolerance or diabetes. The effects of GH

  19. Serum level of orexin-A, leptin, adiponectin and insulin in north Indian obese women.

    PubMed

    Mishra, Sameeksha; Gupta, Vani; Mishra, Supriya; Sachan, Rekha; Asthana, Akash

    2017-12-01

    Obesity is regulated by different metabolic factors like leptin, adiponectin insulin and neuropeptide orexin-A. The aim of this study is to assess the role of these hormones and their interrelationship with obesity in north Indian women. A total of 168 obese women with Body Mass Index (BMI)>30kg/m 2 and 150 lean women (BMI<25kg/m 2 ) as control were recruited in this study. Women with obesity were further subdivided into two groups according to their BMI, 71 overweight women with the BMI 25-29.9kg/m 2 (mean±S.D: 27.87±0.71) and the 97 obese women with BMI>30kg/m 2 (34.68±1.90). Orexin -A, leptin and adiponectin were estimated using quantitative sandwich enzyme linked immunoassay and insulin was estimated by using an immuno-radiometric assay. Orexin -A and adiponectin level were significantly lower however, leptin and inulin level were significantly higher in obese women as compared with control group. Further, the one- way group analysis showed that the orexin -A and adiponectin level were significantly lower but leptin and insulin level was significantly higher in obese women as compared to overweight and control group respectively. Result showed that the level of adiponectin, leptin, orexin-A and insulin play an important role in the regulation of energy expenditure. In obesity, the activity of these peptides is disturbed. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  20. Food fried in extra-virgin olive oil improves postprandial insulin response in obese, insulin-resistant women.

    PubMed

    Farnetti, Sara; Malandrino, Noemi; Luciani, Davide; Gasbarrini, Giovanni; Capristo, Esmeralda

    2011-03-01

    The benefits of low glycemic load (GL) diets on clinical outcome in several metabolic and cardiovascular diseases have extensively been demonstrated. The GL of a meal can be affected by modulating the bioavailability of carbohydrates or by changing food preparation. We investigated the effect on plasma glucose and insulin response in lean and obese women of adding raw or fried extra-virgin olive oil to a carbohydrate-containing meal. After an overnight fast, 12 obese insulin-resistant women (body mass index [BMI], 32.8 ± 2.2 kg/m(2)) and five lean subjects (BMI, 22.2 ± 1.2 kg/m(2)) were randomly assigned to receive two different meals (designated A and B). Meal A was composed of 60 g of pasta made from wheat flour and 150 g of grilled courgettes with 25 g of uncooked oil. Meal B included 15 g of oil in the 150 g of deep-fried courgettes and 10 g of oil in the 60 g of stir-fried pasta. Both meals included 150 g of apple. Blood samples were collected at baseline and every 30 minutes over a 3-hour post-meal period and were tested for levels of glucose, insulin, C-peptide, and triglycerides. The area under the curve (AUC) values were calculated. In obese women the AUCs for C-peptide were significantly higher after meal A than after meal B at 120 minutes (W [Wilcoxon sign rank test] = 27.5, P = .0020), 150 minutes (W = 26.5, P = .0039), and 180 minutes (W = 26.5, P = .0039). No differences were found in lean subjects. This study demonstrated that in obese, insulin-resistant women, food fried in extra-virgin olive oil significantly reduced both insulin and C-peptide responses after a meal.

  1. Survey of abdominal obesities in an adult urban population of Kinshasa, Democratic Republic of Congo

    PubMed Central

    Kasiam Lasi On’kin, JB; Longo-Mbenza, B; Okwe, A Nge; Kabangu, N Kangola

    2007-01-01

    Summary Background The prevalence of overweight/obesity, which is an important cardiovascular risk factor, is rapidly increasing worldwide. Abdominal obesity, a fundamental component of the metabolic syndrome, is not defined by appropriate cutoff points for sub-Saharan Africa. Objective To provide baseline and reference data on the anthropometry/body composition and the prevalence rates of obesity types and levels in the adult urban population of Kinshasa, DRC, Central Africa. Methods During this cross-sectional study carried out within a random sample of adults in Kinshasa town, body mass index, waist circumference and fatty mass were measured using standard methods. Their reference and local thresholds (cut-off points) were compared with those of WHO, NCEP and IFD to define the types and levels of obesity in the population. Results From this sample of 11 511 subjects (5 676 men and 5 835 women), the men presented with similar body mass index and fatty mass values to those of the women, but higher waist measurements. The international thresholds overestimated the prevalence of denutrition, but underscored that of general and abdominal obesity. The two types of obesity were more prevalent among women than men when using both international and local thresholds. Body mass index was negatively associated with age; but abdominal obesity was more frequent before 20 years of age and between 40 and 60 years old. Local thresholds of body mass index (≥ 23, ≥ 27 and ≥ 30 kg/m2) and waist measurement (≥ 80, ≥ 90 and ≥ 94 cm) defined epidemic rates of overweight/general obesity (52%) and abdominal obesity (40.9%). The threshold of waist circumference ≥ 94 cm (90th percentile) corresponding to the threshold of the body mass index ≥ 30 kg/m2 (90th percentile) was proposed as the specific threshold of definition of the metabolic syndrome, without reference to gender, for the cities of sub-Saharan Africa. Conclusion Further studies are required to define the

  2. Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors.

    PubMed

    Meyer, M R; Clegg, D J; Prossnitz, E R; Barton, M

    2011-09-01

    Obesity increases the risk of coronary artery disease through insulin resistance, diabetes, arterial hypertension and dyslipidemia. The prevalence of obesity has increased worldwide and is particularly high among middle-aged women and men. After menopause, women are at an increased risk to develop visceral obesity due to the loss of endogenous ovarian hormone production. Effects of oestrogens are classically mediated by the two nuclear oestrogen receptors (ERs) α and β. In addition, more recent research has shown that the intracellular transmembrane G-protein-coupled oestrogen receptor (GPER) originally designated as GPR30 also mediates some of the actions attributed to oestrogens. Oestrogen and its receptors are important regulators of body weight and insulin sensitivity not only in women but also in men as demonstrated by ER mutations in rodents and humans. This article reviews the role of sex hormones and ERs in the context of obesity, insulin sensitivity and diabetes as well as the related clinical issues in women and men. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  3. Spontaneously obese dogs exhibit greater postprandial glucose, triglyceride, and insulin concentrations than lean dogs.

    PubMed

    Verkest, K R; Rand, J S; Fleeman, L M; Morton, J M

    2012-02-01

    Dogs do not appear to progress from obesity-induced insulin resistance to type 2 diabetes mellitus. Both postprandial hyperglycemia and postprandial hypertriglyceridemia have been proposed to cause or maintain beta cell failure and progression to type 2 diabetes mellitus in other species. Postprandial glucose, triglyceride, and insulin concentrations have not been compared in lean and obese dogs. We measured serum glucose, triglyceride, and insulin concentrations in nine naturally occurring obese and nine age- and gender-matched lean dogs. After a 24-h fast, dogs were fed half their calculated daily energy requirement of a standardized diet that provided 37% and 40% of metabolizable energy as carbohydrate and fat, respectively. Fasting and postprandial glucose and triglyceride concentrations were greater in the obese dogs (P < 0.001), although the mean insulin concentration for this group was five times greater than that of the lean group (P < 0.001). Most of the 0.6 mM (11 mg/dL) difference in mean postprandial glucose concentrations between lean and obese dogs was attributable to a subset of persistently hyperglycemic obese dogs with mean postprandial glucose concentrations 1.0 mM (18 mg/dL) greater than that in lean dogs. Persistently hyperglycemic obese dogs had lower triglyceride (P = 0.02 to 0.04) and insulin (P < 0.02) concentrations than other obese dogs. None of the dogs developed clinical signs of diabetes mellitus during follow-up for a median of 2.6 yr. We conclude that pancreatic beta cells in dogs are either not sensitive to toxicity because of mild hyperglycemia or lack another component of the pathophysiology of beta cell failure in type 2 diabetes mellitus. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Association between duration of overall and abdominal obesity beginning in young adulthood and coronary artery calcification in middle age.

    PubMed

    Reis, Jared P; Loria, Catherine M; Lewis, Cora E; Powell-Wiley, Tiffany M; Wei, Gina S; Carr, J Jeffrey; Terry, James G; Liu, Kiang

    2013-07-17

    Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity. To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease. Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985-1986 who did not initially have overall obesity (body mass index [BMI] ≥30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline. Presence of CAC was measured by computed tomography at the year 15 (2000-2001), year 20 (2005-2006), or year 25 (2010-2011) follow-up examinations. Ten-year progression of CAC (2000-2001 to 2010-2011) was defined as incident CAC in 2010-2011 or an increase in CAC score of 20 Agatston units or greater. During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC for each additional year of overall or abdominal obesity were 1.02 (95% CI, 1.01-1.03) and 1.03 (95% CI

  5. Excessive Refined Carbohydrates and Scarce Micronutrients Intakes Increase Inflammatory Mediators and Insulin Resistance in Prepubertal and Pubertal Obese Children Independently of Obesity

    PubMed Central

    López-Alarcón, Mardia; Perichart-Perera, Otilia; Rodríguez-Cruz, Maricela; Armenta-Álvarez, Andrea; Bram-Falcón, María Teresa; Mayorga-Ochoa, Marielle

    2014-01-01

    Background. Low-grade inflammation is the link between obesity and insulin resistance. Because physiologic insulin resistance occurs at puberty, obese pubertal children are at higher risk for insulin resistance. Excessive diets in refined carbohydrates and saturated fats are risk factors for insulin resistance, but calcium, magnesium, vitamin-D, and the omega-3 fatty acids likely protect against inflammation and insulin resistance. Objective. To analyze interactions among dietary saturated fat, refined carbohydrates, calcium, magnesium, vitamin D, and omega-3 fatty acids on the risk of inflammation and insulin resistance in a sample of prepubertal and pubertal children. Methods. A sample of 229 children from Mexico City was analyzed in a cross-sectional design. Anthropometric measurements, 24 h recall questionnaires, and blood samples were obtained. Serum insulin, glucose, calcium, magnesium, 25-OHD3, C-reactive protein, leptin, adiponectin, and erythrocytes fatty acids were measured. Parametric and nonparametric statistics were used for analysis. Results. While mean macronutrients intake was excessive, micronutrients intake was deficient (P < 0.01). Inflammation determinants were central obesity and magnesium-deficient diets. Determinants of insulin resistance were carbohydrates intake and circulating magnesium and adiponectin. Conclusions. Magnesium-deficient diets are determinants of inflammation, while high intake of refined carbohydrates is a risk factor for insulin resistance, independently of central adiposity. PMID:25477716

  6. Abdominal Obesity and Risk of Hip Fracture: A Systematic Review and Meta-Analysis of Prospective Studies.

    PubMed

    Sadeghi, Omid; Saneei, Parvaneh; Nasiri, Morteza; Larijani, Bagher; Esmaillzadeh, Ahmad

    2017-09-01

    Data on the association between general obesity and hip fracture were summarized in a 2013 meta-analysis; however, to our knowledge, no study has examined the association between abdominal obesity and the risk of hip fracture. The present systematic review and meta-analysis of prospective studies was undertaken to summarize the association between abdominal obesity and the risk of hip fracture. We searched online databases for relevant publications up to February 2017, using relevant keywords. In total, 14 studies were included in the systematic review and 9 studies, with a total sample size of 295,674 individuals (129,964 men and 165,703 women), were included in the meta-analysis. Participants were apparently healthy and aged ≥40 y. We found that abdominal obesity (defined by various waist-hip ratios) was positively associated with the risk of hip fracture (combined RR: 1.24, 95% CI: 1.05, 1.46, P = 0.01). Combining 8 effect sizes from 6 studies, we noted a marginally significant positive association between abdominal obesity (defined by various waist circumferences) and the risk of hip fracture (combined RR: 1.36; 95% CI: 0.97, 1.89, P = 0.07). This association became significant in a fixed-effects model (combined effect size: 1.40, 95% CI: 1.25, 1.58, P < 0.001). Based on 5 effect sizes, we found that a 0.1-U increase in the waist-hip ratio was associated with a 16% increase in the risk of hip fracture (combined RR: 1.16, 95% CI: 1.04, 1.29, P = 0.007), whereas a 10-cm increase in waist circumference was not significantly associated with a higher risk of hip fracture (combined RR: 1.13, 95% CI: 0.94, 1.36, P = 0.19). This association became significant, however, when we applied a fixed-effects model (combined effect size: 1.21, 95% CI: 1.15, 1.27, P < 0.001). We found that abdominal obesity was associated with a higher risk of hip fracture in 295,674 individuals. Further studies are needed to test whether there are associations between abdominal obesity and

  7. Skin disorders in overweight and obese patients and their relationship with insulin.

    PubMed

    Plascencia Gómez, A; Vega Memije, M E; Torres Tamayo, M; Rodríguez Carreón, A A

    2014-03-01

    The prevalence of obesity has increased worldwide in recent years. Some authors have described skin conditions associated with obesity, but there is little evidence on the association between insulin levels and such disorders. To describe the skin disorders present in overweight and obese patients and analyze their association with insulin levels. The study included nondiabetic male and female patients over 6 years of age who were seen at our hospital between January and April 2011. All the patients were evaluated by a dermatologist, who performed a physical examination, including anthropometry, and reviewed their medical history and medication record; fasting blood glucose and insulin were also measured. The patients were grouped according to degree of overweight or obesity and the data were compared using analysis of variance or the χ(2) test depending on the type of variable. The independence of the associations was assessed using regression analysis. In total, 109 patients (95 adults and 13 children, 83.5% female) were studied. The mean (SD) age was 38 (14) years and the mean body mass index was 39.6±8 kg/m(2). The skin conditions observed were acanthosis nigricans (AN) (in 97% of patients), skin tags (77%), keratosis pilaris (42%), and plantar hyperkeratosis (38%). Statistically significant associations were found between degree of obesity and AN (P=.003), skin tags (P=.001), and plantar hyperkeratosis. Number of skin tags, AN neck severity score, and AN distribution were significantly and independently associated with insulin levels. AN and skin tags should be considered clinical markers of hyperinsulinemia in nondiabetic, obese patients. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

  8. Fanconi anemia links reactive oxygen species to insulin resistance and obesity.

    PubMed

    Li, Jie; Sipple, Jared; Maynard, Suzette; Mehta, Parinda A; Rose, Susan R; Davies, Stella M; Pang, Qishen

    2012-10-15

    Insulin resistance is a hallmark of obesity and type 2 diabetes. Reactive oxygen species (ROS) have been proposed to play a causal role in insulin resistance. However, evidence linking ROS to insulin resistance in disease settings has been scant. Since both oxidative stress and diabetes have been observed in patients with the Fanconi anemia (FA), we sought to investigate the link between ROS and insulin resistance in this unique disease model. Mice deficient for the Fanconi anemia complementation group A (Fanca) or Fanconi anemia complementation group C (Fancc) gene seem to be diabetes-prone, as manifested by significant hyperglycemia and hyperinsulinemia, and rapid weight gain when fed with a high-fat diet. These phenotypic features of insulin resistance are characterized by two critical events in insulin signaling: a reduction in tyrosine phosphorylation of the insulin receptor (IR) and an increase in inhibitory serine phosphorylation of the IR substrate-1 in the liver, muscle, and fat tissues from the insulin-challenged FA mice. High levels of ROS, spontaneously accumulated or generated by tumor necrosis factor alpha in these insulin-sensitive tissues of FA mice, were shown to underlie the FA insulin resistance. Treatment of FA mice with the natural anti-oxidant Quercetin restores IR signaling and ameliorates the diabetes- and obesity-prone phenotypes. Finally, pairwise screen identifies protein-tyrosine phosphatase (PTP)-α and stress kinase double-stranded RNA-dependent protein kinase (PKR) that mediate the ROS effect on FA insulin resistance. These findings establish a pathogenic and mechanistic link between ROS and insulin resistance in a unique human disease setting. ROS accumulation contributes to the insulin resistance in FA deficiency by targeting both PTP-α and PKR.

  9. Physical activity level of postmenopausal women in Nigeria: Association with self-rated health status, overall obesity, and abdominal obesity.

    PubMed

    Ogwumike, Omoyemi O; Adeniyi, Ade F; Orogbemi, Oluwakemi O

    2016-07-01

    Regular physical activity (PA) has been shown to have many health benefits in various populations, including postmenopausal women (n = 310). Self-rated health has been positively associated with PA. This cross-sectional survey of postmenopausal women in Nigeria was conducted from April to September 2012 to investigate associations among PA level, self-rated health, overall obesity (body mass index [BMI]), and abdominal obesity (waist-height ratio, waist-hip ratio, and waist circumference). The International Physical Activity Questionnaire was used to classify PA. Chi-square and logistic regression were used for analyses with level of significance set at .05. Participants were aged 53.0 ± 4.2 years; moderate to vigorous PA was reported by 188 (60.0%), while 26 (8.4%) self-rated their health as poor/fair, and 242 (78.1%) were either predominantly overweight or obese when classified according to BMI. Participants with fair/poor self-rated health had less odds of involvement in moderate to vigorous PA. Obese postmenopausal women had greater odds of reporting lower PA. PA was positively related to self-rated health, which was negatively associated with overall obesity but not abdominal obesity. Measures to control obesity among postmenopausal women are essential in view of its direct association with poor self-rated health and low PA in this group of women.

  10. Protein kinases: mechanisms and downstream targets in inflammation mediated obesity and insulin resistance

    PubMed Central

    Nandipati, Kalyana C; Subramanian, Saravanan; Agrawal, Devendra K

    2016-01-01

    Obesity induced low-grade inflammation (metaflammation) impairs insulin receptor signaling (IRS). This has been implicated in the development of insulin resistance. Insulin signaling in the target tissues is mediated by stress kinases such as p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), inhibitor of NF-kB kinase complex beta (IKKβ), AMP activated protein kinase (AMPK), protein kinase C (PKC), Rho associated coiled-coil containing protein kinase (ROCK) and RNA-activated protein kinase (PKR), etc. Most of these kinases phosphorylate several key regulators in glucose homeostasis. The phosphorylation of serine residues in the insulin receptor (IR) and IRS-1 molecule results in diminished enzymatic activity in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This has been one of the key mechanisms observed in the tissues that are implicated in insulin resistance especially in Type II Diabetes Mellitus (T2-DM). Identifying the specific protein kinases involved in obesity induced chronic inflammation may help in developing the targeted drug therapies to minimize the insulin resistance. This review is focused on the protein kinases involved in the inflammatory cascade and molecular mechanisms and their downstream targets with special reference to obesity induced T2-DM. PMID:27868170

  11. Lipocalin-2 Deficiency Attenuates Insulin Resistance Associated With Aging and Obesity

    PubMed Central

    Law, Ivy K.M.; Xu, Aimin; Lam, Karen S.L.; Berger, Thorsten; Mak, Tak W.; Vanhoutte, Paul M.; Liu, Jacky T.C.; Sweeney, Gary; Zhou, Mingyan; Yang, Bo; Wang, Yu

    2010-01-01

    OBJECTIVE The proinflammatory cytokines/adipokines produced from adipose tissue act in an autocrine and/or endocrine manner to perpetuate local inflammation and to induce peripheral insulin resistance. The present study investigates whether lipocalin-2 deficiency or replenishment with this adipokine has any impact on systemic insulin sensitivity and the underlying mechanisms. METHODS AND RESULTS Under conditions of aging or dietary-/genetic-induced obesity, lipocalin-2 knockout (Lcn2-KO) mice show significantly decreased fasting glucose and insulin levels and improved insulin sensitivity compared with their wild-type littermates. Despite enlarged fat mass, inflammation and the accumulation of lipid peroxidation products are significantly attenuated in the adipose tissues of Lcn2-KO mice. Adipose fatty acid composition of these mice varies significantly from that in wild-type animals. The amounts of arachidonic acid (C20:4 n6) are elevated by aging and obesity and are paradoxically further increased in adipose tissue, but not skeletal muscle and liver of Lcn2-KO mice. On the other hand, the expression and activity of 12-lipoxygenase, an enzyme responsible for metabolizing arachidonic acid, and the production of tumor necrosis factor-α (TNF-α), a critical insulin resistance–inducing factor, are largely inhibited by lipocalin-2 deficiency. Lipocalin-2 stimulates the expression and activity of 12-lipoxygenase and TNF-α production in fat tissues. Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC), an arachidonate lipoxygenase inhibitor, prevents TNF-α expression induced by lipocalin-2. Moreover, treatment with TNF-α neutralization antibody or CDC significantly attenuated the differences of insulin sensitivity between wild-type and Lcn2-KO mice. CONCLUSIONS Lipocalin-2 deficiency protects mice from developing aging- and obesity-induced insulin resistance largely by modulating 12-lipoxygenase and TNF-α levels in adipose tissue. PMID:20068130

  12. Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade.

    PubMed

    Pedersen, Morten Høgild; Svart, Mads Vandsted; Lebeck, Janne; Bidlingmaier, Martin; Stødkilde-Jørgensen, Hans; Pedersen, Steen Bønløkke; Møller, Niels; Jessen, Niels; Jørgensen, Jens O L

    2017-04-01

    Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance. To study the metabolic effects of GH blockade during fasting in obese subjects. Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies. GH levels increased with fasting (P < 0.01), and the fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P < 0.05). Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P < 0.01) primarily due to reduced endogenous glucose production (P = 0.003). Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA. Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects. Copyright © 2017 by the Endocrine Society

  13. Sex-Specific Difference in the Association Between Poor Sleep Quality and Abdominal Obesity in Rural Chinese: A Large Population-Based Study.

    PubMed

    Liu, Ru-Qing; Qian, Zhengmin; Wang, Si-Quan; Vaughn, Michael G; Geiger, Sarah Dee; Xian, Hong; Lin, Shao; Paul, Gunther; Zeng, Xiao-Wen; Yang, Bo-Yi; Hu, Li-Wen; Xu, Shu-Li; Yang, Mo; Dong, Guang-Hui

    2017-04-15

    Existing studies on sleep quality and associated obesity are inconsistent, and few studies have prospectively evaluated the association between sleep quality and abdominal obesity among Chinese individuals. To fill this void, the current study aimed to assess the association between sleep quality and abdominal obesity in a rural Chinese population. A representative sample of 9,404 adults aged 20-93 years in northeastern China was selected between 2012 and 2013 by a multistage cluster and random sampling method. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI), where a score of 6 or higher indicated sleep disorder. Abdominal obesity was measured by waist circumference (WC), with abdominal obesity defined as WC > 90 cm for men and WC > 80 cm for women. Male participants with abdominal obesity had higher global PSQI scores in addition to higher subscores in almost all of the elements compared to normal values. The odds ratios of abdominal obesity among participants with sleep disorders were 1.64 (95% confidence interval [CI]: 1.39-1.95) and 1.14 (95% CI: 0.98-1.32) for males and females compared to the reference group. The risk in all sleep elements was significantly increased, with odds ratios ranging from 1.28 (95% CI: 1.08-1.51) to 5.81 (95% CI: 3.54-9.53) for males. The risk only in four elements was significantly increased, from 1.28 (95% CI: 1.12-1.47) to 2.27 (95% CI: 1.36-3.80) for females. Poor sleep quality was associated with abdominal obesity in Chinese. Furthermore, effects in males were larger than those in females. © 2017 American Academy of Sleep Medicine

  14. Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration.

    PubMed

    Spielman, Lindsay J; Little, Jonathan P; Klegeris, Andis

    2014-08-15

    Obesity is a growing epidemic that contributes to several brain disorders including Alzheimer's, Parkinson's, and Huntington's diseases. Obesity could promote these diseases through several different mechanisms. Here we review evidence supporting the involvement of two recently recognized factors linking obesity with neurodegeneration: the induction of pro-inflammatory cytokines and onset of insulin and insulin-like growth factor 1 (IGF-1) resistance. Excess peripheral pro-inflammatory mediators, some of which can cross the blood brain barrier, may trigger neuroinflammation, which subsequently exacerbates neurodegeneration. Insulin and IGF-1 resistance leads to weakening of neuroprotective signaling by these molecules and can contribute to onset of neurodegenerative diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Abdominal obesity validates the association between elevated alanine aminotransferase and newly diagnosed diabetes mellitus.

    PubMed

    Yueh, Chen-Yu; Yang, Yao-Hsu; Sung, Yi-Ting; Lee, Li-Wen

    2014-01-01

    To examine how elevated alanine aminotransferase (ALT) could be associated with newly diagnosed diabetes mellitus. We conducted a cross-sectional analysis on a mass health examination. The odds ratios (ORs) for diabetes mellitus and newly diagnosed diabetes mellitus were compared between people with and without abdominal obesity, together with and without elevated ALT levels. 5499 people were included in this study. Two hundred fifty two (4.6%) fulfilled the diagnosis of diabetes mellitus with 178 (3.2%) undiagnosed before. Metabolic syndrome was vigorously associated with diabetes mellitus and newly diagnosed diabetes mellitus (12.4% vs. 1.4% and 9.0% vs. 0.9%), but elevated ALT alone was not. However, coexisting with obesity, elevated ALTs were robustly associated with diabetes mellitus and newly diagnosed diabetes mellitus. For the incidence of newly diagnosed diabetes mellitus, in comparison to non-obese people with normal ALT (1.7%, OR = 1), obese people especially with elevated ALT levels had significantly higher ORs (obese with ALT ≤ 40 U/L: 4.7%, OR 1.73, 95% CI 1.08-2.77, P 0.023; ALT 41-80 U/L: 6.8%, OR 2.06, 95% CI 1.20-3.55, P 0.009; ALT 81-120 U/L: 8.8%, OR 3.07, 95% CI 1.38-6.84, P 0.006; ALT > 120 U/L: 18.2%, OR 7.44, 95% CI 3.04-18.18, P < 0.001). Abdominal obesity validates the association between elevated alanine aminotransferase and diabetes mellitus and newly diagnosed diabetes mellitus. People with abdominal obesity, especially with coexisting elevated ALT levels should be screened for undiagnosed diabetes mellitus.

  16. Sexual dimorphism in interleukin 17A and adipocytokines and their association with insulin resistance among obese adolescents in Yogyakarta, Indonesia.

    PubMed

    Susilowati, Rina; Sulistyoningrum, Dian Caturini; Witari, Ni Putu Diah; Huriyati, Emy; Luglio, Harry Freitag; Julia, Madarina

    2016-12-01

    Pro-inflammatory cytokines interleukin 17A (IL-17), leptin, and adiponectin have been associated with obesity and insulin resistance. Moreover, differences in sex and ethnicity as well as plasma concentration of adipocytokines and cytokines have been associated with the risk of insulin resistance. This study was conducted to elucidate whether sex differences exist in the risk of insulin resistance in Indonesian adolescents and to determine how plasma leptin, adiponectin, and IL-17 predict insulin resistance. The study participants were 69 obese-overweight boys, 53 obese-overweight girls, 59 non-obese boys, and 50 non-obese girls aged 15-18 years. Insulin resistance was determined using the homeostatic model assessment of insulin resistance index. Plasma IL-17, leptin, and adiponectin were measured using ELISA. Data were analysed using one-way ANOVA and linear regression analysis. Odd ratios [ORs; 95% confidence intervals (CIs)] were analysed to estimate the risk of insulin resistance; the significance level was set at 95%. The OR (95% CI) for insulin resistance was higher in obese-overweight boys than in obese-overweight girls. The plasma IL-17 was higher in boys, whereas plasma adiponectin and leptin were significantly higher in girls. In all participants, obesity status and plasma leptin were the most efficient predictors of insulin resistance, whereas the IL-17 could not significantly predict insulin resistance. Sexual dimorphism exists in IL17 as well as leptin and adiponectin in adolescents. Plasma IL-17 cannot be used to predict insulin resistance in adolescents of both sex.

  17. Reversal of diet-induced obesity and insulin resistance by inducible genetic ablation of GRK2

    PubMed Central

    Vila-Bedmar, Rocio; Cruces-Sande, Marta; Lucas, Elisa; Willemen, Hanneke L.D.M.; Heijnen, Cobi J.; Kavelaars, Annemieke; Mayor, Federico; Murga, Cristina

    2015-01-01

    Insulin resistance is a common feature of obesity and predisposes individuals to various prevalent pathological conditions. G protein-coupled receptor kinase 2 (GRK2) integrates several signal transduction pathways and is emerging as a physiologically relevant inhibitor of insulin signaling. GRK2 abundanceis increased in humans with metabolic syndrome and in different murine models of insulin resistance. To support GRK2 as a potential drug target in type 2 diabetes and obesity, we investigated whether lowering GRK2 abundance reversed an ongoing systemic insulin-resistant phenotype, using a mouse model of tamoxifen-induced GRK2 ablation after high fat diet-dependent obesity and insulin resistance. Tamoxifen-triggered GRK2 deletion impeded further body weight gain, normalized fa sting glycemia, improved glucose tolerance and was associated with preserved insulin sensitivity in skeletal muscle and liver, thereby maintaining whole body glucose homeostasis. Moreover, when continued to be fed a high fat diet, these animals displayed reduced fat mass and smaller adipocytes, were resistant to the development of liver steatosis, and showed reduced expression of pro-inflammatory markers in the liver. Our results indicate that GRK2 acts as a hub to control metabolic functions in different tissues, which is key to controlling insulin resistance development in vivo. These data suggest that inhibiting GRK2 could reverse an established insulin-resistant and obese phenotype, thereby putting forward this enzyme as a potential therapeutic target linking glucose homeostasis and regulation of adiposity. PMID:26198359

  18. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    NASA Astrophysics Data System (ADS)

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  19. Obesity is the main determinant of insulin resistance more than the circulating pro-inflammatory cytokines levels in rheumatoid arthritis patients.

    PubMed

    Castillo-Hernandez, Jesus; Maldonado-Cervantes, Martha Imelda; Reyes, Juan Pablo; Patiño-Marin, Nuria; Maldonado-Cervantes, Enrique; Solorzano-Rodriguez, Claudia; de la Cruz Mendoza, Esperanza; Alvarado-Sanchez, Brenda

    Systemic blockade of TNF-α in Rheumatoid arthritis with insulin resistance seems to produce more improvement in insulin sensitivity in normal weight patients with Rheumatoid arthritis than in obese patients with Rheumatoid arthritis, suggesting that systemic-inflammation and obesity are independent risk factors for insulin resistance in Rheumatoid arthritis patients. To evaluate the insulin resistance in: normal weight patients with Rheumatoid arthritis, overweight patients with Rheumatoid arthritis, obese Rheumatoid arthritis patients, and matched control subjects with normal weight and obesity; and its association with major cytokines involved in the pathogenesis of the disease. Assessments included: body mass index, insulin resistance by Homeostasis Model Assessment, ELISA method, and enzymatic colorimetric assay. Outstanding results from these studies include: (1) In Rheumatoid arthritis patients, insulin resistance was well correlated with body mass index, but not with levels of serum cytokines. In fact, levels of cytokines were similar in all Rheumatoid arthritis patients, regardless of being obese, overweight or normal weight (2) Insulin resistance was significantly higher in Rheumatoid arthritis with normal weight than in normal weight (3) No significant difference was observed between insulin resistances of Rheumatoid arthritis with obesity and obesity (4) As expected, levels of circulating cytokines were significantly higher in Rheumatoid arthritis patients than in obesity. Obesity appears to be a dominant condition above inflammation to produce IR in RA patients. The dissociation of the inflammation and obesity components to produce IR suggests the need of an independent therapeutic strategy in obese patients with RA. Copyright © 2017. Published by Elsevier Editora Ltda.

  20. Catalpic acid decreases abdominal fat deposition, improves glucose homeostasis and upregulates PPAR alpha expression in adipose tissue.

    PubMed

    Hontecillas, Raquel; Diguardo, Maggie; Duran, Elisa; Orpi, Marcel; Bassaganya-Riera, Josep

    2008-10-01

    Catalpic acid (CAT) is a conjugated linolenic acid (CLN) isomer containing trans-9, trans-11, cis-13 double bonds in an 18-carbon chain and it is found primarily in the seed oil of ornamental and medicinal trees and shrubs of the family Bignoniaceae. The objective of this study was to investigate whether CAT decreases obesity and ameliorates insulin sensitivity and glucose tolerance in mice fed high-fat diets. To test the efficacy of CAT in decreasing obesity and diabetes we used both a model of diet-induced obesity (DIO) and a genetic model of obesity (i.e., mice lacking the leptin receptor). Blood was collected on days 0, 7, 14, 21 and 28 for determining fasting glucose and insulin concentrations in plasma. In addition, a glucose tolerance test was administered on day 28. We found that dietary CAT (1g/100g) decreased fasting plasma glucose and insulin concentrations, ameliorated the glucose normalizing ability following glucose challenge and decreased abdominal white adipose tissue accumulation. In white adipose tissue (WAT), CAT upregulated peroxisome proliferator-activated receptor (PPAR) alpha and its responsive genes [i.e., stearoyl-coenzyme A desaturase (SCD1) and enoyl-coenzyme A hydratase (ECH)], increased concentrations of high-density lipoprotein (HDL) cholesterol and decreased plasma triglyceride (TG) levels. CAT decreased abdominal fat deposition, increased HDL cholesterol, decreased TG concentrations, decreased glucose and insulin homeostasis and modulated WAT gene expression in a manner reminiscent of the actions of the PPAR alpha-activating fibrate class of lipid-lowering drugs.

  1. Defective Insulin Signalling, Mediated by Inflammation, Connects Obesity to Alzheimer Disease; Relevant Pharmacological Therapies and Preventive Dietary Interventions.

    PubMed

    Rodriguez-Casado, Arantxa; Toledano-Díaz, Adolfo; Toledano, Adolfo

    2017-01-01

    Recent evidence suggests that obesity, besides being a risk factor for cardiovascular events, also increases the risk of Alzheimer's disease. Insulin resistance is common in all cases of obesity and appears to be the linkage between both diseases. Obesity, often associated with excessive fat and sugar intake, represents a preclinical stage toward insulin resistance during which nutrition intervention is likely to have maximum effect. In this way, healthy lifestyles lifetime to prevent obesity-related modifiable risk factors such as inflammation, oxidative stress and metabolic disorders could be simultaneously beneficial for preserving cognition and controlling the Alzheimer's disease. This review relates extensive research literature on facts linking nutrients and dietary patterns to obesity and Alzheimer's disease. In addition briefly presents molecular mechanisms involved in obesity- induced insulin resistance and the contribution of peripheral inflammatory and defective insulin signalling pathways, as well as ectopic lipids accumulation to Alzheimer's development through brain inflammation, neuronal insulin resistance, and cognitive dysfunction seen in Alzheimer's disease. The work relates current and emerging pharmacological and non-pharmacological therapies for the management of obesity, insulin resistance and Alzheimer's considering them as disorders with common molecular features. The findings of this review validate the importance of some nutritional interventions as possible approach to prevent or delay simultaneously progression of Alzheimer's disease and obesity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Cardiometabolic risk factors and insulin resistance in obese children and adolescents: relation to puberty.

    PubMed

    Tobisch, B; Blatniczky, L; Barkai, L

    2015-02-01

    The prevalence of obesity with concomitant increasing risk for having cardiometabolic diseases is rising in the childhood population. Insulin resistance has a key role in metabolic changes in these children. Insulin levels elevate as puberty commences in every individual. Children with increased risk for cardiometabolic diseases show significant differences in insulin levels even before the onset of puberty compared with those without risks. The pattern of appearance of dyslipidaemia also varies in children with risk factors even in the pre-pubertal group from those without risk. Children with metabolic syndrome display considerably pronounced changes in their metabolic parameters before the onset of puberty, which become more pronounced as puberty passes. Insulin resistance (IR) has a key role in the metabolic changes in obese children. In commencing puberty, the insulin levels elevate. It is not clear, however, how insulin levels develop if the metabolic syndrome appears. Metabolic changes were assessed in obese children before, during and after puberty to analyse the relationship between IR and puberty in subjects with and without metabolic syndrome. Three hundred thirty-four obese children (5-19 years) attended the study. The criteria of the International Diabetes Federation were used to assess the presence of cardiometabolic risks (CMRs). Subjects with increased CMR were compared with those without risk (nCMR). Pubertal staging, lipid levels, plasma glucose and insulin levels during oral glucose tolerance test were determined in each participant. IR was expressed by homeostasis model assessment (HOMA-IR) and the ratio of glucose and insulin areas under the curve (AUC-IR). Significantly higher AUC-IR were found in pre-pubertal CMR children compared with nCMR subjects (11.84 ± 1.03 vs. 8.00 ± 0.69; P < 0.01), but no difference was discovered during and after puberty. HOMA-IR differs between CMR and nCMR only in post-puberty (6.03 ± 1.26 vs. 2

  3. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men.

    PubMed Central

    Fried, S K; Russell, C D; Grauso, N L; Brolin, R E

    1993-01-01

    There are marked variations in the activity of lipoprotein lipase (LPL) among adipose depots, particularly in women. Consistent with data on LPL activity, the level of expression of LPL mRNA was lower in omental (OM) than subcutaneous (SQ) adipose tissue of women. To investigate the cellular basis of these differences, OM and SQ adipose tissues obtained at surgery from obese men and women were placed in organ culture for 7 d with varying concentrations of insulin and dexamethasone. Insulin increased levels of LPL mRNA and LPL activity in abdominal SQ but not OM adipose tissue. Dexamethasone also increased LPL mRNA and LPL activity, and these effects were more marked in the OM adipose tissue, particularly in men. When insulin and dexamethasone were added together, synergistic increases in LPL activity were seen in both depots, and this was in part explained at the level of LPL mRNA. The SQ depot was more sensitive to the effects of submaximal doses of dexamethasone in the presence of insulin. The maximum activity of LPL induced by insulin or insulin plus dexamethasone was higher in the SQ than in the OM depot of women, and this was associated with higher levels of LPL mRNA. Rates of LPL synthesis paralleled LPL mRNA levels. These data show that insulin and glucocorticoids influence human adipose tissue LPL activity at the level of LPL gene expression, as well as posttranslationally, and that responsiveness to these hormonal effects is dependent on adipose depot and gender. Images PMID:8227334

  4. Fanconi Anemia Links Reactive Oxygen Species to Insulin Resistance and Obesity

    PubMed Central

    Li, Jie; Sipple, Jared; Maynard, Suzette; Mehta, Parinda A.; Rose, Susan R.; Davies, Stella M.

    2012-01-01

    Abstract Aims: Insulin resistance is a hallmark of obesity and type 2 diabetes. Reactive oxygen species (ROS) have been proposed to play a causal role in insulin resistance. However, evidence linking ROS to insulin resistance in disease settings has been scant. Since both oxidative stress and diabetes have been observed in patients with the Fanconi anemia (FA), we sought to investigate the link between ROS and insulin resistance in this unique disease model. Results: Mice deficient for the Fanconi anemia complementation group A (Fanca) or Fanconi anemia complementation group C (Fancc) gene seem to be diabetes-prone, as manifested by significant hyperglycemia and hyperinsulinemia, and rapid weight gain when fed with a high-fat diet. These phenotypic features of insulin resistance are characterized by two critical events in insulin signaling: a reduction in tyrosine phosphorylation of the insulin receptor (IR) and an increase in inhibitory serine phosphorylation of the IR substrate-1 in the liver, muscle, and fat tissues from the insulin-challenged FA mice. High levels of ROS, spontaneously accumulated or generated by tumor necrosis factor alpha in these insulin-sensitive tissues of FA mice, were shown to underlie the FA insulin resistance. Treatment of FA mice with the natural anti-oxidant Quercetin restores IR signaling and ameliorates the diabetes- and obesity-prone phenotypes. Finally, pairwise screen identifies protein-tyrosine phosphatase (PTP)-α and stress kinase double-stranded RNA-dependent protein kinase (PKR) that mediate the ROS effect on FA insulin resistance. Innovation: These findings establish a pathogenic and mechanistic link between ROS and insulin resistance in a unique human disease setting. Conclusion: ROS accumulation contributes to the insulin resistance in FA deficiency by targeting both PTP-α and PKR. Antioxid. Redox Signal. 00, 000–000. PMID:22482891

  5. Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance.

    PubMed

    Nishimoto, Sachiko; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Murata, Chie; Kim-Kaneyama, Joo-Ri; Sato, Fukiko; Bando, Masahiro; Yagi, Shusuke; Soeki, Takeshi; Hayashi, Tetsuya; Imoto, Issei; Sakaue, Hiroshi; Shimabukuro, Michio; Sata, Masataka

    2016-03-01

    Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9 (-/-) ) macrophages. Fat-fed Tlr9 (-/-) mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9 (-/-) mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography-determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.

  6. Association Between Duration of Overall and Abdominal Obesity Beginning in Young Adulthood and Coronary Artery Calcification in Middle Age

    PubMed Central

    Reis, Jared P.; Loria, Catherine M.; Lewis, Cora E.; Powell-Wiley, Tiffany M.; Wei, Gina S.; Carr, J. Jeffrey; Terry, James G.; Liu, Kiang

    2014-01-01

    IMPORTANCE Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity. OBJECTIVE To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985–1986 who did not initially have overall obesity (body mass index [BMI] ≥30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline. MAIN OUTCOMES AND MEASURES Presence of CAC was measured by computed tomography at the year 15 (2000–2001), year 20 (2005–2006), or year 25 (2010–2011) follow-up examinations. Ten-year progression of CAC (2000–2001 to 2010–2011) was defined as incident CAC in 2010–2011 or an increase in CAC score of 20 Agatston units or greater. RESULTS During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC

  7. Caloric Restriction and Diet-Induced Weight Loss Do Not Induce Browning of Human Subcutaneous White Adipose Tissue in Women and Men with Obesity.

    PubMed

    Barquissau, Valentin; Léger, Benjamin; Beuzelin, Diane; Martins, Frédéric; Amri, Ez-Zoubir; Pisani, Didier F; Saris, Wim H M; Astrup, Arne; Maoret, Jean-José; Iacovoni, Jason; Déjean, Sébastien; Moro, Cédric; Viguerie, Nathalie; Langin, Dominique

    2018-01-23

    Caloric restriction (CR) is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white adipose tissue (WAT). Here, human subcutaneous abdominal WAT samples were analyzed in 289 individuals with obesity following a two-phase dietary intervention consisting of an 8 week very low calorie diet and a 6-month weight-maintenance phase. Before the intervention, we show sex differences and seasonal variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Abdominal obesity and all-cause and cardiovascular mortality in end-stage renal disease.

    PubMed

    Postorino, Maurizio; Marino, Carmen; Tripepi, Giovanni; Zoccali, Carmine

    2009-04-14

    The aim of this study was to investigate the predictive value for all-cause and cardiovascular (CV) death of anthropometric measurements of abdominal obesity in patients with end-stage renal disease (ESRD). Surrogate measures of abdominal obesity and segmental fat distribution (waist circumference and waist/hip ratio [WHR]) are stronger predictors of all-cause and CV death than body mass index (BMI) in the general population, but the issue has never been investigated in patients with ESRD. We performed a prospective cohort study in 537 patients with ESRD (age 63 +/- 15 years). In BMI-adjusted Cox models, waist circumference was a direct predictor of all-cause and CV mortality (p < 0.001), whereas BMI showed an inverse relationship (p < 0.001) with these outcomes. The incidence rates of overall and CV death were maximal in patients with relatively lower BMI scores (below the median) and higher waist circumferences (at least the median) and minimal in patients with higher BMI scores (at least the median) and small waist circumferences (below the median). The prognostic power of waist circumference for all-cause (hazard ratio [HR] [10-cm increase]: 1.23; 95% confidence interval [CI]: 1.02 to 1.47; p = 0.03) and CV mortality (HR: 1.37; 95% CI: 1.09 to 1.73; p = 0.006) remained significant after adjustment for CV comorbidities and traditional and emerging risk factors. WHR was found to be related to all-cause (p = 0.009) and CV mortality (p = 0.07). Abdominal obesity underlies a high risk of all-cause and CV mortality in patients with ESRD. Redefinition of nutritional status by combining the metrics of abdominal obesity and BMI may refine prognosis in the ESRD population.

  9. Beneficial effect of baicalin on insulin sensitivity in adipocytes of diet-induced obese mice.

    PubMed

    Fang, Penghua; Yu, Mei; Min, Wen; Han, Shiyu; Shi, Mingyi; Zhang, Zhenwen; Bo, Ping

    2018-05-01

    Although baicalin has been shown to increase glucose uptake and insulin sensitivity in skeletal muscle of mice, there is no literature available about the effect of baicalin on insulin sensitivity in adipocytes of diet-induced obese mice. In the present study, diet-induced obese mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 days, and 3T3-L1 cells were treated with 100, 200, 400 μM baicalin for 3 h. Then insulin resistance indexes and insulin signal protein levels were examined to elucidate whether baicalin increased glucose uptake and GLUT4 translocation in adipocytes of diet-induced obese mice. The present findings showed that administration of baicalin decreased food intake, body weight, HOMA-IR and p-p38 MAPK and pERK levels, but enhanced pAKT and PGC-1α contents, as well as GLUT4 mRNA, PGC-1α mRNA expression in adipocytes, and reversed high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Moreover, baicalin treatment increased GLUT4 concentration in plasma membranes of adipocytes. These data demonstrated that baicalin accelerated GLUT4 translocation from intracellular membrane compartments to plasma membranes in adipocytes. Baicalin plays a significant role in elevation of glucose uptake and insulin sensitivity to promote glucose clearance. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin.

    PubMed

    Balani, Jyoti; Hyer, Steve; Syngelaki, Argyro; Akolekar, Ranjit; Nicolaides, Kypros H; Johnson, Antoinette; Shehata, Hassan

    2017-12-01

    To examine whether the reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is mediated by changes in insulin resistance. This was a secondary analysis of obese pregnant women in a randomised trial (MOP trial). Fasting plasma glucose and insulin were measured in 384 of the 400 women who participated in the MOP trial. Homeostasis model assessment of insulin resistance (HOMA-IR) was compared in the metformin and placebo groups and in those that developed preeclampsia versus those that did not develop preeclampsia. At 28 weeks, median HOMA-IR was significantly lower in the metformin group. Logistic regression analysis demonstrated that there was a significant contribution in the prediction of preeclampsia from maternal history of chronic hypertension and gestational weight gain, but not HOMA-IR either at randomisation ( p  = 0.514) or at 28 weeks ( p  = 0.643). Reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is unlikely to be due to changes in insulin resistance.

  11. Fasting serum insulin and the homeostasis model of insulin resistance (HOMA-IR) in the monitoring of lifestyle interventions in obese persons.

    PubMed

    Vogeser, Michael; König, Daniel; Frey, Ingrid; Predel, Hans-Georg; Parhofer, Klaus Georg; Berg, Aloys

    2007-09-01

    Lifestyle changes with increased physical activity and balanced energy intake are recognized as the principal interventions in obesity and insulin resistance. Only few prospective studies, however, have so far addressed the potential role of routine biochemical markers of insulin sensitivity in the monitoring of respective interventions. Fasting insulin and glucose was measured in 33 obese individuals undergoing a lifestyle modification program (MOBILIS) at baseline and after 1 year. The HOMA-IR index (homeostasis model of insulin resistance) was calculated as [fasting serum glucose*fasting serum insulin/22.5], with lower values indicating a higher degree of insulin sensitivity. While the median body mass index (BMI) and waist circumference decreased by 10% and 11%, respectively, the HOMA-IR index decreased in an over-proportional manner by 45% within 1 year (BMI baseline, median 35.7, interquartile range (IQR) 33.7-37.7; after 1 year, median 32.2, IQR 29.6-35.1. HOMA-IR baseline, median 2.9, IQR 1.5-4.6; after 1 year 1.6, IQR 0.9-2.7). In contrast to HOMA-IR and fasting serum insulin, no significant changes in fasting serum glucose were observed. Baseline and post-intervention HOMA-IR showed a high degree of inter-individual variation with eight individuals maintaining high HOMA-IR values despite weight loss after 1 year of intervention. Individual changes in the carbohydrate metabolism achieved by a lifestyle intervention program were displayed by fasting serum insulin concentrations and the HOMA-IR but not by fasting glucose measurement alone. Therefore, assessment of the HOMA-IR may help to individualize lifestyle interventions in obesity and to objectify improvements in insulin sensitivity after therapeutic lifestyle changes.

  12. Relation of insulin resistance to neurocognitive function and electroencephalography in obese children.

    PubMed

    Akın, Onur; Eker, İbrahim; Arslan, Mutluay; Yavuz, Süleyman Tolga; Akman, Sevil; Taşçılar, Mehmet Emre; Ünay, Bülent

    2017-10-26

    Childhood obesity may lead to neuronal impairment in both the peripheral and the central nervous system. This study aimed to investigate the impact of obesity and insulin resistance (IR) on the central nervous system and neurocognitive functions in children. Seventy-three obese children (38 male and 35 female) and 42 healthy children (21 male and 21 female) were recruited. Standard biochemical indices and IR were evaluated. The Wechsler Intelligence Scale for Children-Revised (WISC-R) and electroencephalography (EEG) were administered to all participants. The obese participants were divided into two groups based on the presence or absence of IR, and the data were compared between the subgroups. Only verbal scores on the WISC-R in the IR+ group were significantly lower than those of the control and IR- groups. There were no differences between the groups with respect to other parameters of the WISC-R or the EEG. Verbal scores of the WISC-R were negatively correlated with obesity duration and homeostatic model assessment-insulin resistance (HOMA-IR) values. EEGs showed significantly more frequent 'slowing during hyperventilation' (SDHs) in obese children than non-obese children. Neurocognitive functions, particularly verbal abilities, were impaired in obese children with IR. An early examination of cognitive functions may help identify and correct such abnormalities in obese children.

  13. Glutathione depletion prevents diet-induced obesity and enhances insulin sensitivity.

    PubMed

    Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L; Cohn, Dianne; Heywood, Elizabeth B; Bruemmer, Dennis

    2011-12-01

    Excessive accumulation of reactive oxygen species (ROS) in adipose tissue has been implicated in the development of insulin resistance and type 2 diabetes. However, emerging evidence suggests a physiologic role of ROS in cellular signaling and insulin sensitivity. In this study, we demonstrate that pharmacologic depletion of the antioxidant glutathione in mice prevents diet-induced obesity, increases energy expenditure and locomotor activity, and enhances insulin sensitivity. These observations support a beneficial role of ROS in glucose homeostasis and warrant further research to define the regulation of metabolism and energy balance by ROS.

  14. Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese horses with insulin resistance.

    PubMed

    Frank, Nicholas; Elliott, Sarah B; Brandt, Laura E; Keisler, Duane H

    2006-05-01

    To compare obese horses with insulin resistance (IR) with nonobese horses and determine whether blood resting glucose, insulin, leptin, and lipid concentrations differed between groups and were correlated with combined glucose-insulin test (CGIT) results. 7 obese adult horses with IR (OB-IR group) and 5 nonobese mares. Physical measurements were taken, and blood samples were collected after horses had acclimated to the hospital for 3 days. Response to insulin was assessed by use of the CGIT, and maintenance of plasma glucose concentrations greater than the preinjection value for > or = 45 minutes was used to define IR. Area under the curve values for glucose (AUC(g)) and insulin (AUC(i)) concentrations were calculated. Morgan, Paso Fino, Quarter Horse, and Tennessee Walking Horse breeds were represented in the OB-IR group. Mean neck circumference and BCS differed significantly between groups and were positively correlated with AUC values. Resting insulin and leptin concentrations were 6 and 14 times as high, respectively, in the OB-IR group, compared with the nonobese group, and were significantly correlated with AUC(g) and AUC(i). Plasma nonesterified fatty acid, very low-density lipoprotein, and high-density lipoprotein-cholesterol (HDL-C) concentrations were significantly higher (86%, 104%, and 29%, respectively) in OB-IR horses, and HDL-C concentrations were positively correlated with AUC values. Measurements of neck circumference and resting insulin and leptin concentrations can be used to screen obese horses for IR. Dyslipidemia is associated with IR in obese horses.

  15. Abdominal adiposity, general obesity, and subclinical systolic dysfunction in the elderly: A population-based cohort study.

    PubMed

    Russo, Cesare; Sera, Fusako; Jin, Zhezhen; Palmieri, Vittorio; Homma, Shunichi; Rundek, Tatjana; Elkind, Mitchell S V; Sacco, Ralph L; Di Tullio, Marco R

    2016-05-01

    General obesity, measured by body mass index (BMI), and abdominal adiposity, measured as waist circumference (WC) and waist-to-hip ratio (WHR), are associated with heart failure and cardiovascular events. However, the relationship of general and abdominal obesity with subclinical left ventricular (LV) dysfunction is unknown. We assessed the association of general and abdominal obesity with subclinical LV systolic dysfunction in a population-based elderly cohort. Participants from the Cardiovascular Abnormalities and Brain Lesions study underwent measurement of BMI, WC, and WHR. Left ventricular systolic function was assessed by two-dimensional echocardiographic LV ejection fraction (LVEF) and speckle-tracking global longitudinal strain (GLS). The study population included 729 participants (mean age 71 ± 9 years, 60% women). In multivariate analysis, higher BMI (but not WC and WHR) was associated with higher LVEF (β = 0.11, P = 0.003). Higher WC (β = 0.08, P = 0.038) and higher WHR (β = 0.15, P < 0.001) were associated with lower GLS, whereas BMI was not (P = 0.720). Compared with normal WHR, high WHR was associated with lower GLS in all BMI categories (normal, overweight, and obese), and was associated with subclinical LV dysfunction by GLS both in participants without [adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.6, P = 0.020] and with general obesity (adjusted OR 5.4, 95% CI 1.1-25.9, P = 0.034). WHR was incremental to BMI and risk factors in predicting LV dysfunction. Abdominal adiposity was independently associated with subclinical LV systolic dysfunction by GLS in all BMI categories. BMI was not associated with LV dysfunction. Increased abdominal adiposity may be a risk factor for LV dysfunction regardless of the presence of general obesity. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  16. Abdominal obesity is associated with heart disease in dogs

    PubMed Central

    2014-01-01

    Background The relationship between overall obesity and fat distribution in dogs and the development of heart disease is unclear. In the present study we evaluated the association between overall obesity and fat distribution and clinical heart disease by morphometric and computed tomography (CT)-based measurements. Body condition score (BCS), modified body mass index (MBMI, kg/m2), waist-to-hock-to-stifle distance ratio (WHSDR), waist-to-ilium wing distance ratio (WIWDR), and waist-to-truncal length ratio (WTLR) were compared between dogs with (n = 44) and without (n = 43) heart disease using receiver operating characteristic (ROC) analysis. Intra-abdominal fat (IAF) and subcutaneous fat (SQF) were measured in dogs with (n = 8) and without (n = 9) heart disease at the center of the fourth and fifth lumbar vertebrae by CT. Results BCS was similar between heart disease and healthy groups (3.6 ± 0.2 vs. 3.3 ± 0.1, P = 0.126). The following morphometric measurements were greater in the heart disease group compared with healthy canines: MBMI (65.0 ± 4.5 vs. 52.5 ± 3.7 kg/m2, respectively, P = 0.035); WIWDR (4.1 ± 0.1 vs. 3.1 ± 0.1, P < 0.01); and WTLR (1.25 ± 0.04 vs. 1.05 ± 0.04, P < 0.01). However, there was no significant difference in WHSDR (3.6 ± 0.1 vs. 3.7 ± 0.2, P = 0.875). Interestingly, IAF was significantly increased in dogs with heart disease compared with healthy dogs (23.5 ± 1.5% vs. 19.4 ± 1.2%, P = 0.039) whereas SQF was similar between two groups (35.5 ± 2.7% vs. 38.6 ± 3.5%, P = 0.496). Of the five morphometric indices studied, WIWDR and WTLR provided acceptable discrimination for diagnosing heart disease in dogs, with areas under the ROC curve of 0.778 (95% confidence interval [CI]:0.683-0.874) and 0.727 (95% CI:0.619-0.835), respectively. Conclusions Our data indicate that abdominal obesity, rather than overall obesity, is associated

  17. Abdominal obesity is associated with heart disease in dogs.

    PubMed

    Thengchaisri, Naris; Theerapun, Wutthiwong; Kaewmokul, Santi; Sastravaha, Amornrate

    2014-06-13

    The relationship between overall obesity and fat distribution in dogs and the development of heart disease is unclear. In the present study we evaluated the association between overall obesity and fat distribution and clinical heart disease by morphometric and computed tomography (CT)-based measurements. Body condition score (BCS), modified body mass index (MBMI, kg/m2), waist-to-hock-to-stifle distance ratio (WHSDR), waist-to-ilium wing distance ratio (WIWDR), and waist-to-truncal length ratio (WTLR) were compared between dogs with (n = 44) and without (n = 43) heart disease using receiver operating characteristic (ROC) analysis. Intra-abdominal fat (IAF) and subcutaneous fat (SQF) were measured in dogs with (n = 8) and without (n = 9) heart disease at the center of the fourth and fifth lumbar vertebrae by CT. BCS was similar between heart disease and healthy groups (3.6 ± 0.2 vs. 3.3 ± 0.1, P = 0.126). The following morphometric measurements were greater in the heart disease group compared with healthy canines: MBMI (65.0 ± 4.5 vs. 52.5 ± 3.7 kg/m2, respectively, P = 0.035); WIWDR (4.1 ± 0.1 vs. 3.1 ± 0.1, P < 0.01); and WTLR (1.25 ± 0.04 vs. 1.05 ± 0.04, P < 0.01). However, there was no significant difference in WHSDR (3.6 ± 0.1 vs. 3.7 ± 0.2, P = 0.875). Interestingly, IAF was significantly increased in dogs with heart disease compared with healthy dogs (23.5 ± 1.5% vs. 19.4 ± 1.2%, P = 0.039) whereas SQF was similar between two groups (35.5 ± 2.7% vs. 38.6 ± 3.5%, P = 0.496). Of the five morphometric indices studied, WIWDR and WTLR provided acceptable discrimination for diagnosing heart disease in dogs, with areas under the ROC curve of 0.778 (95% confidence interval [CI]:0.683-0.874) and 0.727 (95% CI:0.619-0.835), respectively. Our data indicate that abdominal obesity, rather than overall obesity, is associated with heart disease in dogs

  18. Add on Exenatide Treatment is Beneficial in Poorly Controlled Obese Type 2 Diabetics under Intensive Insulin Regimens.

    PubMed

    Sönmez, Alper; Dinç, Mustafa; Taşlıpınar, Abdullah; Aydoğdu, Aydogan; Meriç, Coskun; Başaran, Yalcin; Haymana, Cem; Demir, Orhan; Yılmaz, İlker; Azal, Ömer

    2017-04-01

    Background: Intensive insulin treatment is bothersome in obese patients with type 2 diabetes mellitus. High insulin dosages further increase weight gain and the risk of hypoglycemia. Glucagon like peptide-1 receptor agonists decrease the insulin need, cause weight loss and reduce the risk of hypoglycemia. There is limited data about the effect of exenatide on obese diabetics under intensive insulin regimens. Methods: This retrospective case series report the clinical outcomes of 23 obese (13 morbidly obese) patients with uncontrolled type 2 diabetes mellitus (Age=59±10.44 years, body mass index 41.1±6.8 kg/m 2 , HbA1c 9.9±1.5%), under high dose (94.1±39.6 unit) intensive insulin. Exenatide twice daily was added for a mean follow-up period of 11.22±7.01 (3-30) months. Intensive insulin regimens were continued in 7 patients while the others were switched to basal insulin during the follow-up. Results: During the follow-up, mean HbA1c levels of the patients significantly improved (p=0.019), along with the significant decrease in body mass index and the total insulin need (p<0.001 for both). Baseline insulin dosages were significantly higher in the intensive regimen group (p=0.013) while other demographical and clinical characteristics were similar. No significant difference was present between the groups regarding the alterations of HbA1c, body mass index and the reduction in total insulin dosages. Conclusion: Add on exenatide appears to be a rational treatment modality in uncontrolled obese patients with type 2 diabetes mellitus despite intensive insulin regimens. Further prospective randomized studies with longer follow-up periods are recommended. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Neuropeptide Y genotype, central obesity, and abdominal fat distribution: the POUNDS LOST trial.

    PubMed

    Lin, Xiaochen; Qi, Qibin; Zheng, Yan; Huang, Tao; Lathrop, Mark; Zelenika, Diana; Bray, George A; Sacks, Frank M; Liang, Liming; Qi, Lu

    2015-08-01

    Neuropeptide Y is a key peptide affecting adiposity and has been related to obesity risk. However, little is known about the role of NPY variations in diet-induced change in adiposity. The objective was to examine the effects of NPY variant rs16147 on central obesity and abdominal fat distribution in response to dietary interventions. We genotyped a functional NPY variant rs16147 among 723 participants in the Preventing Overweight Using Novel Dietary Strategies trial. Changes in waist circumference (WC), total abdominal adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue (SAT) from baseline to 6 and 24 mo were evaluated with respect to the rs16147 genotypes. Genotype-dietary fat interaction was also examined. The rs16147 C allele was associated with a greater reduction in WC at 6 mo (P < 0.001). In addition, the genotypes showed a statistically significant interaction with dietary fat in relation to WC and SAT (P-interaction = 0.01 and 0.04): the association was stronger in individuals with high-fat intake than in those with low-fat intake. At 24 mo, the association remained statistically significant for WC in the high-fat diet group (P = 0.02), although the gene-dietary fat interaction became nonsignificant (P = 0.30). In addition, we found statistically significant genotype-dietary fat interaction on the change in total abdominal adipose tissue, visceral adipose tissue, and SAT at 24 mo (P = 0.01, 0.05, and 0.04): the rs16147 T allele appeared to associate with more adverse change in the abdominal fat deposition in the high-fat diet group than in the low-fat diet group. Our data indicate that the NPY rs16147 genotypes affect the change in abdominal adiposity in response to dietary interventions, and the effects of the rs16147 single-nucleotide polymorphism on central obesity and abdominal fat distribution were modified by dietary fat. © 2015 American Society for Nutrition.

  20. The effect of dietary fiber and other factors on insulin response: role in obesity.

    PubMed

    Ullrich, I H; Albrink, M J

    1985-07-01

    Epidemiologic evidence favors the hypothesis that obesity may result from the fiber-depleted diet of industrialized societies. Since hyperinsulinemia is a universal characteristic and perhaps causal of obesity, the possibility is considered that dietary factors causing excess insulin secretion might lead to obesity. Dietary glucose causes a slightly greater insulin rise than cooked starch containing an equal amount of carbohydrate, and high fiber starchy foods cause a much lesser insulin response than does glucose in solution. Doubling the dose of carbohydrate in a meal causes only a small increase in glucose response but a large increase in insulin response. Dietary fiber could act by displacing some of the carbohydrate that would normally be absorbable in the small intestine, or could translocate the carbohydrate to a point lower in the intestinal tract where less effect on insulin secretion would be observed. Evidence is presented that a higher fiber diet is associated with a higher concentration of fasting circulating free fatty acids, a lesser post-cibal decrease in circulating free fatty acids and triglycerides and less chronic increase in fasting triglycerides than a low fiber diet. These differences are associated with a lesser insulin response to high fiber meals. The extreme fluctuations between the fed and fasted states seen with low fiber diets are thus dampened by high fiber diets. The less complete inhibition of lipolysis during the fed state, and more intense lipolysis during fasting, suggested by the above data, might tend to prevent obesity. The mechanisms of the lesser insulin response to high rather than low fiber meals are not known, but the possibility that dietary fiber decreases the GIP response is considered.

  1. First national epidemiological survey on the prevalence of obesity and abdominal fat distribution in Greek adults.

    PubMed

    Kapantais, E; Tzotzas, T; Ioannidis, I; Mortoglou, A; Bakatselos, S; Kaklamanou, M; Lanaras, L; Kaklamanos, I

    2006-01-01

    To provide estimates of the prevalence of obesity, overweight and body fat distribution among the adult population of Greece. Epidemiological, cross-sectional nationwide survey providing self-reported data. A total of 17,341 men and women aged from 20 to 70 years and classified into five 10-year age groups participated. The selection was conducted by stratified sampling through household family members of Greek children attending school. The participants reported data on weight, height, waist and hip circumference. BMI and waist-to-hip ratio were calculated. Abdominal obesity was defined as waist circumference > or = 102 cm in men and > or = 88 cm in women. In the total population, the mean BMI was 26.5 kg/m2, (27.3 in men, 25.7 in women). The overall prevalence of obesity was 22.5%, (26% in men, 18.2% in women) while that of overweight was 35.2% (41.1% in men, 29.9% in women). The percentages of obesity and overweight in men were similar in almost all age groups, while in women they progressively increased with age. Abdominal obesity was more frequent among women than men (35.8 vs. 26.6%, respectively), especially after the age of 50. Excess body weight is reaching epidemic proportions in Greece and obesity rates are among the highest, if not the highest, in Western society. The problem affects particularly men, and women after menopause. Interestingly, more women than men present with abdominal obesity. Preventive and treatment strategies are urgently needed to stop the obesity epidemic in this Mediterranean European country. Copyright 2006 S. Karger AG, Basel.

  2. Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.

    PubMed

    Tuulari, Jetro J; Karlsson, Henry K; Hirvonen, Jussi; Hannukainen, Jarna C; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

    2013-08-01

    Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

  3. Early-life stress and the development of obesity and insulin resistance in juvenile bonnet macaques.

    PubMed

    Kaufman, Daniel; Banerji, Mary Ann; Shorman, Igor; Smith, Eric L P; Coplan, Jeremy D; Rosenblum, Leonard A; Kral, John G

    2007-05-01

    Stress is a risk factor for chronic illnesses such as obesity, type 2 diabetes, and hypertension and has been postulated to cause the metabolic syndrome via perturbation of the hypothalamo-pituitary-adrenal (HPA) axis. In our model of early-life stress (variable foraging demand [VFD]), food insecurity is imposed on monkey mothers for 16 weeks beginning when their nursing offspring are 3-5 months of age. Under VFD, food availability is never restricted, and the infant's growth is unaffected. VFD rearing does, however, cause a range of neurobiological abnormalities, including dysregulation of the HPA axis, manifested in abnormal cerebrospinal fluid cortisol and corticotropin-releasing factor levels. We previously reported spontaneous occurrence of metabolic syndrome in 14% of normally reared peripubertal bonnet macaques given ad libitum access to standard monkey chow. Here, we show that compared with normally reared monkeys, peripubertal VFD juveniles exhibit greater weight, BMI, abdominal circumference, and glucagon-like peptide-1 and decreased glucose disposal rates during hyperinsulinemic-euglycemic clamps. Our data suggest that early-life stress during a critical period of neuro development can result in the peripubertal emergence of obesity and insulin resistance.

  4. Loss of prion protein is associated with the development of insulin resistance and obesity.

    PubMed

    de Brito, Giovanna; Lupinacci, Fernanda C; Beraldo, Flávio H; Santos, Tiago G; Roffé, Martín; Lopes, Marilene H; de Lima, Vladmir C; Martins, Vilma R; Hajj, Glaucia N

    2017-08-17

    Prion protein (PrP C ) was initially described due to its involvement in transmissible spongiform encephalopathies. It was subsequently demonstrated to be a cell surface molecule involved in many physiological processes, such as vesicle trafficking. Here, we investigated the roles of PrP C in the response to insulin and obesity development. Two independent PrP C knockout (KO) and one PrP C overexpressing (TG20) mouse models were fed high-fat diets, and the development of insulin resistance and obesity was monitored. PrP C KO mice fed high-fat diets presented all of the symptoms associated with the development of insulin resistance: hyperglycemia, hyperinsulinemia, and obesity. Conversely, TG20 animals fed high-fat diets showed reduced weight and insulin resistance. Accordingly, the expression of peroxisome proliferator-activated receptor gamma (PPARγ) was reduced in PrP C KO mice and increased in TG20 animals. PrP C KO cells also presented reduced glucose uptake upon insulin stimulation, due to reduced translocation of the glucose transporter Glut4. Thus, our results suggest that PrP C reflects susceptibility to the development of insulin resistance and metabolic syndrome. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  5. Blocking CXCR7-mediated adipose tissue macrophages chemotaxis attenuates insulin resistance and inflammation in obesity.

    PubMed

    Peng, Hongxia; Zhang, Hu; Zhu, Honglei

    2016-10-28

    Adipose tissue macrophages (ATMs) have been considered to have a pivotal role in the chronic inflammation development during obesity. Although chemokine-chemokine receptor interaction has been studied in ATMs infiltration, most chemokine receptors remain incompletely understood and little is known about their mechanism of actions that lead to ATMs chemotaxis and pathogenesis of insulin resistance during obesity. In this study, we reported that CXCR7 expression is upregulated in adipose tissue, and specifically in ATMs during obesity. In addition, CXCL11 or CXCL12-induced ATMs chemotaxis is mediated by CXCR7 in obesity but not leanness, whereas CXCR3 and CXCR4 are not involved. Additional mechanism study shows that NF-κB activation is essential in ATMs chemotaxis, and manipulates chemotaxis of ATMs via CXCR7 expression regulation in obesity. Most importantly, CXCR7 neutralizing therapy dose dependently leads to less infiltration of macrophages into adipose tissue and thus reduces inflammation and improves insulin sensitivity in obesity. In conclusion, these findings demonstrated that blocking CXCR7-mediated ATMs chemotaxis ameliorates insulin resistance and inflammation in obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management.

    PubMed

    Misra, A; Chowbey, P; Makkar, B M; Vikram, N K; Wasir, J S; Chadha, D; Joshi, Shashank R; Sadikot, S; Gupta, R; Gulati, Seema; Munjal, Y P

    2009-02-01

    Asian Indians exhibit unique features of obesity; excess body fat, abdominal adiposity, increased subcutaneous and intra-abdominal fat, and deposition of fat in ectopic sites (liver, muscle, etc.). Obesity is a major driver for the widely prevalent metabolic syndrome and type 2 diabetes mellitus (T2DM) in Asian Indians in India and those residing in other countries. Based on percentage body fat and morbidity data, limits of normal BMI are narrower and lower in Asian Indians than in white Caucasians. In this consensus statement, we present revised guidelines for diagnosis of obesity, abdominal obesity, the metabolic syndrome, physical activity, and drug therapy and bariatric surgery for obesity in Asian Indians after consultations with experts from various regions of India belonging to the following medical disciplines; internal medicine, metabolic diseases, endocrinology, nutrition, cardiology, exercise physiology, sports medicine and bariatric surgery, and representing reputed medical institutions, hospitals, government funded research institutions, and policy making bodies. It is estimated that by application of these guidelines, additional 10-15% of Indian population would be labeled as overweight/obese and would require appropriate management. Application of these guidelines on countrywide basis is also likely to have a deceleration effect on the escalating problem of T2DM and cardiovascular disease. These guidelines could be revised in future as appropriate, after another large and countrywide consensus process. Till that time, these should be used by clinicians, researchers and policymakers dealing with obesity and related diseases.

  7. Metabolic signatures of insulin resistance in 7,098 young adults.

    PubMed

    Würtz, Peter; Mäkinen, Ville-Petteri; Soininen, Pasi; Kangas, Antti J; Tukiainen, Taru; Kettunen, Johannes; Savolainen, Markku J; Tammelin, Tuija; Viikari, Jorma S; Rönnemaa, Tapani; Kähönen, Mika; Lehtimäki, Terho; Ripatti, Samuli; Raitakari, Olli T; Järvelin, Marjo-Riitta; Ala-Korpela, Mika

    2012-06-01

    Metabolite associations with insulin resistance were studied in 7,098 young Finns (age 31 ± 3 years; 52% women) to elucidate underlying metabolic pathways. Insulin resistance was assessed by the homeostasis model (HOMA-IR) and circulating metabolites quantified by high-throughput nuclear magnetic resonance spectroscopy in two population-based cohorts. Associations were analyzed using regression models adjusted for age, waist, and standard lipids. Branched-chain and aromatic amino acids, gluconeogenesis intermediates, ketone bodies, and fatty acid composition and saturation were associated with HOMA-IR (P < 0.0005 for 20 metabolite measures). Leu, Ile, Val, and Tyr displayed sex- and obesity-dependent interactions, with associations being significant for women only if they were abdominally obese. Origins of fasting metabolite levels were studied with dietary and physical activity data. Here, protein energy intake was associated with Val, Phe, Tyr, and Gln but not insulin resistance index. We further tested if 12 genetic variants regulating the metabolites also contributed to insulin resistance. The genetic determinants of metabolite levels were not associated with HOMA-IR, with the exception of a variant in GCKR associated with 12 metabolites, including amino acids (P < 0.0005). Nonetheless, metabolic signatures extending beyond obesity and lipid abnormalities reflected the degree of insulin resistance evidenced in young, normoglycemic adults with sex-specific fingerprints.

  8. [Rational therapy of patients with essential hypertension and abdominal obesity with concomitant subclinical hypothyroidism].

    PubMed

    Pligovka, V M

    2014-11-01

    It was determined the characteristics of lipid status of patients with essential hypertension, abdominal obesity with concomitant subclinical hypothyroidism--mostly increased levels of total and LDL cholesterol. In assessing the effectiveness of statin therapy in combination with levothyroxine replacement therapy compared with statin monotherapy, combination therapy showed the best result in terms of achievement of target levels of both total cholesterol and LDL. The obtained results allow us to recommend the use of combination therapy for patients with hypertension, abdominal obesity with concomitant subclinical hypothyroidism in order to achieve the target values of LDL and thus to reduce the cardiovascular risk of these patients.

  9. Proteasome Dysfunction Associated to Oxidative Stress and Proteotoxicity in Adipocytes Compromises Insulin Sensitivity in Human Obesity

    PubMed Central

    Díaz-Ruiz, Alberto; Guzmán-Ruiz, Rocío; Moreno, Natalia R.; García-Rios, Antonio; Delgado-Casado, Nieves; Membrives, Antonio; Túnez, Isaac; El Bekay, Rajaa; Fernández-Real, José M.; Tovar, Sulay; Diéguez, Carlos; Tinahones, Francisco J.; Vázquez-Martínez, Rafael; López-Miranda, José

    2015-01-01

    Abstract Aims: Obesity is characterized by a low-grade systemic inflammatory state and adipose tissue (AT) dysfunction, which predispose individuals to the development of insulin resistance (IR) and metabolic disease. However, a subset of obese individuals, referred to as metabolically healthy obese (MHO) individuals, are protected from obesity-associated metabolic abnormalities. Here, we aim at identifying molecular factors and pathways in adipocytes that are responsible for the progression from the insulin-sensitive to the insulin-resistant, metabolically unhealthy obese (MUHO) phenotype. Results: Proteomic analysis of paired samples of adipocytes from subcutaneous (SC) and omental (OM) human AT revealed that both types of cells are altered in the MUHO state. Specifically, the glutathione redox cycle and other antioxidant defense systems as well as the protein-folding machinery were dysregulated and endoplasmic reticulum stress was increased in adipocytes from IR subjects. Moreover, proteasome activity was also compromised in adipocytes of MUHO individuals, which was associated with enhanced accumulation of oxidized and ubiquitinated proteins in these cells. Proteasome activity was also impaired in adipocytes of diet-induced obese mice and in 3T3-L1 adipocytes exposed to palmitate. In line with these data, proteasome inhibition significantly impaired insulin signaling in 3T3-L1 adipocytes. Innovation: This study provides the first evidence of the occurrence of protein homeostasis deregulation in adipocytes in human obesity, which, together with oxidative damage, interferes with insulin signaling in these cells. Conclusion: Our results suggest that proteasomal dysfunction and impaired proteostasis in adipocytes, resulting from protein oxidation and/or misfolding, constitute major pathogenic mechanisms in the development of IR in obesity. Antioxid. Redox Signal. 23, 597–612. PMID:25714483

  10. Relationship between neck circumference, insulin resistance and arterial stiffness in overweight and obese subjects.

    PubMed

    Fantin, Francesco; Comellato, Gabriele; Rossi, Andrea P; Grison, Elisa; Zoico, Elena; Mazzali, Gloria; Zamboni, Mauro

    2017-09-01

    Background Only a few studies have investigated the relationship between neck circumference and cardiometabolic risk. The aim of this study was to assess the relationships between neck circumference, waist circumference, metabolic variables and arterial stiffness in a group of overweight and obese subjects evaluating a possible independent role of neck circumference in determining arterial stiffness. Methods and results We studied 95 subjects (53 women) with an age range of 20-77 years and body mass index range from 25.69 to 47.04 kg/m 2 . In each subject we evaluated body mass index, waist, hip and neck circumference, systolic and diastolic blood pressure, insulin, fasting glucose, cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWVcf) and carotid-radial pulse wave velocity (PWVcr). Both PWVcf and PWVcr were higher in subjects with high values of neck circumference compared with subjects with normal values of neck circumference. Subjects with high values of neck circumference and abdominal obesity presented higher values of mean arterial pressure, PWVcr and homeostasis model assessment (HOMA) index and lower values of high-density lipoprotein than subjects with only abdominal obesity. Two models of stepwise multiple regression were performed in order to evaluate the combined effect of independent variables on arterial stiffness. In the first model PWVcf was considered a dependent variable, and age, gender, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, waist circumference, neck circumference, HOMA index and the use of anti-hypertensive medications were considered independent variables. Age, systolic blood pressure, triglycerides and waist circumference were significant predictors of PWVcf, explaining 65% of its variance. In the second model, in which PWVcr was considered a dependent variable, neck circumference

  11. Ghrelin receptor regulates HFCS-induced adipose inflammation and insulin resistance

    PubMed Central

    Ma, X; Lin, L; Yue, J; Pradhan, G; Qin, G; Minze, L J; Wu, H; Sheikh-Hamad, D; Smith, C W; Sun, Y

    2013-01-01

    Background and Objectives: High fructose corn syrup (HFCS) is the most commonly used sweetener in the United States. Some studies show that HFCS consumption correlates with obesity and insulin resistance, while other studies are in disagreement. Owing to conflicting and insufficient scientific evidence, the safety of HFCS consumption remains controversial. Subjects/Methods: We investigated the metabolic consequences of mice fed a (a) regular diet, (b) ‘Western' high-fat diet or (c) regular diet supplemented with 8% HFCS in drinking water (to mimic soft drinks) for 10 months. Adipose tissue macrophages (ATMs) have emerged as a major pathogenic factor for obesity and insulin resistance. ATMs consist of proinflammatory F4/80+CD11c+ macrophages and anti-inflammatory F4/80+CD11c− macrophages. In this study, we assessed the effects of HFCS on ATMs in intra-abdominal fat. Results: We found that HFCS feeding in mice induced more severe adipose inflammation and insulin resistance than even the higher-calorie-containing ‘Western' high-fat diet, and these HFCS-induced deleterious effects were independent of calorie intake or body fat content. We showed that similar to ‘Western' high-fat diet, HFCS triggered a robust increase of both proinflammatory ATMs and anti-inflammatory ATMs in intra-abdominal fat. Remarkably, however, the anti-inflammatory ATMs were much less abundant in HFCS-fed mice than in high-fat-fed mice. Furthermore, we showed that deletion of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) ameliorates HFCS-induced adipose inflammation and insulin resistance. HFCS-fed GHS-R-null mice exhibit decreased proinflammatory ATMs in intra-abdominal fat, reduced adipose inflammation and attenuated liver steatosis. Conclusion: Our studies demonstrate that HFCS has detrimental effects on metabolism, suggesting that dietary guidelines on HFCS consumption for Americans may need to be revisited. GHS-R deletion mitigates the effects of HFCS on adipose

  12. Ghrelin receptor regulates HFCS-induced adipose inflammation and insulin resistance.

    PubMed

    Ma, X; Lin, L; Yue, J; Pradhan, G; Qin, G; Minze, L J; Wu, H; Sheikh-Hamad, D; Smith, C W; Sun, Y

    2013-12-23

    High fructose corn syrup (HFCS) is the most commonly used sweetener in the United States. Some studies show that HFCS consumption correlates with obesity and insulin resistance, while other studies are in disagreement. Owing to conflicting and insufficient scientific evidence, the safety of HFCS consumption remains controversial. We investigated the metabolic consequences of mice fed a (a) regular diet, (b) 'Western' high-fat diet or (c) regular diet supplemented with 8% HFCS in drinking water (to mimic soft drinks) for 10 months. Adipose tissue macrophages (ATMs) have emerged as a major pathogenic factor for obesity and insulin resistance. ATMs consist of proinflammatory F4/80(+)CD11c(+) macrophages and anti-inflammatory F4/80(+)CD11c(-) macrophages. In this study, we assessed the effects of HFCS on ATMs in intra-abdominal fat. We found that HFCS feeding in mice induced more severe adipose inflammation and insulin resistance than even the higher-calorie-containing 'Western' high-fat diet, and these HFCS-induced deleterious effects were independent of calorie intake or body fat content. We showed that similar to 'Western' high-fat diet, HFCS triggered a robust increase of both proinflammatory ATMs and anti-inflammatory ATMs in intra-abdominal fat. Remarkably, however, the anti-inflammatory ATMs were much less abundant in HFCS-fed mice than in high-fat-fed mice. Furthermore, we showed that deletion of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) ameliorates HFCS-induced adipose inflammation and insulin resistance. HFCS-fed GHS-R-null mice exhibit decreased proinflammatory ATMs in intra-abdominal fat, reduced adipose inflammation and attenuated liver steatosis. Our studies demonstrate that HFCS has detrimental effects on metabolism, suggesting that dietary guidelines on HFCS consumption for Americans may need to be revisited. GHS-R deletion mitigates the effects of HFCS on adipose inflammation and insulin resistance, suggesting that GHS

  13. Rosiglitazone Improves Insulin Sensitivity and Baroreflex Gain in Rats with Diet-Induced Obesity

    PubMed Central

    Zhao, Ding; McCully, Belinda H.

    2012-01-01

    Obesity decreases baroreflex gain (BRG); however, the mechanisms are unknown. We tested the hypothesis that impaired BRG is related to the concurrent insulin resistance, and, therefore, BRG would be improved after treatment with the insulin-sensitizing drug rosiglitazone. Male rats fed a high-fat diet diverged into obesity-prone (OP) and obesity-resistant (OR) groups after 2 weeks. Then, OP and OR rats, as well as control (CON) rats fed a standard diet, were treated daily for 2 to 3 weeks with rosiglitazone (3 or 6 mg/kg) or its vehicle by gavage. Compared with OR and CON rats, conscious OP rats exhibited reductions in BRG (OP, 2.9 ± 0.1 bpm/mm Hg; OR, 4.0 ± 0.2 bpm/mm Hg; CON, 3.9 ± 0.2 bpm/mm Hg; P < 0.05) and insulin sensitivity (hyperinsulinemic euglycemic clamp; OP, 6.8 ± 0.9 mg/kg · min; OR, 22.2 ± 1.2 mg/kg · min; CON, 17.7 ± 0.8 mg/kg · min; P < 0.05), which were well correlated (r2 = 0.49; P < 0.01). In OP rats, rosiglitazone dose-dependently improved (P < 0.05) insulin sensitivity (12.8 ± 0.6 mg/kg · min at 3 mg/kg; 16.0 ± 1.5 mg/kg · min at 6 mg/kg) and BRG (3.8 ± 0.4 bpm/mm Hg at 3 mg/kg; 5.3 ± 0.7 bpm/mm Hg at 6 mg/kg). However, 6 mg/kg rosiglitazone also increased BRG in OR rats without increasing insulin sensitivity, disrupted the correlation between BRG and insulin sensitivity (r2 = 0.08), and, in OP and OR rats, elevated BRG relative to insulin sensitivity (analysis of covariance; P < 0.05). Moreover, in OP rats, stimulation of the aortic depressor nerve, to activate central baroreflex pathways, elicited markedly reduced decreases in heart rate and arterial pressure, but these responses were not improved by rosiglitazone. In conclusion, diet-induced obesity impairs BRG via a central mechanism that is related to the concurrent insulin resistance. Rosiglitazone normalizes BRG, but not by improving brain baroreflex processing or insulin sensitivity. PMID:22815534

  14. Serum progranulin levels in relation to insulin resistance in childhood obesity.

    PubMed

    Alissa, Eman M; Sutaih, Rima H; Kamfar, Hayat Z; Alagha, Abdulmoeen E; Marzouki, Zuhair M

    2017-11-27

    Progranulin is an adipokine that is involved in the inflammatory response, glucose metabolism, insulin resistance, and may therefore be involved in chronic subclinical inflammation associated with the pathogenesis of childhood obesity. We aimed to investigate the association of circulating progranulin levels with metabolic parameters in children and to assess the importance of progranulin as a biomarker for metabolic diseases. A total of 150 children were consecutively recruited from the Pediatric Nutrition Clinics at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Children were classified into four groups based on quartile for serum progranulin. Anthropometric variables were measured in all study subjects. Fasting blood samples were collected for measurement of blood glucose, insulin and lipid profile. Children within the upper quartile for serum progranulin concentration were heavier, more insulin resistant and had higher concentrations of serum total cholesterol, triglycerides, insulin and high sensitivity C reactive protein compared to those in the lower quartile. On correlation analysis, serum progranulin concentrations were significantly related to general and central adiposity, metabolic parameters, markers of inflammation and insulin resistance. Stepwise multiple regression showed that 26.6% of the variability in serum progranulin could be explained by measures of adiposity. The increased serum progranulin concentrations were closely related to measures of adiposity, metabolic parameters, inflammatory marker and insulin resistance indices, suggesting that progranulin may be an excellent biomarker for obesity in childhood.

  15. Concentrations of Plasma Free Palmitoleic and Dihomo-Gamma Linoleic Fatty Acids Are Higher in Children with Abdominal Obesity.

    PubMed

    Aristizabal, Juan C; González-Zapata, Laura I; Estrada-Restrepo, Alejandro; Monsalve-Alvarez, Julia; Restrepo-Mesa, Sandra L; Gaitán, Diego

    2018-01-01

    Increased plasma free fatty acids (FFAs) are associated with cardiometabolic risk factors in adults with abdominal obesity (AO). However, this association remains controversial in children. This study analyzed plasma FFA concentration in children with and without AO. Twenty-nine children classified with AO were matched by age and sex with 29 non-obese individuals. Blood samples were collected after fasting for 10-12 h. Plasma concentration of glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined by automatized methods. FFAs were analyzed by gas chromatography. Children with and without AO had similar age (7.1 ± 2.6 vs. 7.2 ± 2.7 years; p > 0.05) but obese children showed higher ( p < 0.05) body mass index (BMI) (+4.3 kg/m²), systolic blood pressure (+5.1 mmHg), and insulin (+27.8 pmol/L). There were no significant differences in plasma total FFA concentration between groups (1.02 ± 0.61 vs. 0.89 ± 0.37 mmol/L; p > 0.05). However, children with AO had higher palmitoleic acid (0.94 vs. 0.70 wt %; p < 0.05) and dihomo-gamma linoleic acid (DHGL) (2.76 vs. 2.07 wt %; p < 0.05). Palmitoleic and DHGL acids correlated ( p < 0.05) with BMI ( r = 0.397; r = 0.296, respectively) and with waist circumference ( r = 0.380; r = 0.276, respectively). Palmitoleic acid correlated positively with systolic blood pressure ( r = 0.386; p < 0.05) and negatively with HDL-C (-0.572; p < 0.01). In summary, children with AO have higher plasmatic concentrations of free palmitoleic and DHGL fatty acids, which correlate with cardiometabolic risk factors.

  16. Concentrations of Plasma Free Palmitoleic and Dihomo-Gamma Linoleic Fatty Acids Are Higher in Children with Abdominal Obesity

    PubMed Central

    González-Zapata, Laura I.; Estrada-Restrepo, Alejandro; Monsalve-Alvarez, Julia; Restrepo-Mesa, Sandra L.; Gaitán, Diego

    2018-01-01

    Increased plasma free fatty acids (FFAs) are associated with cardiometabolic risk factors in adults with abdominal obesity (AO). However, this association remains controversial in children. This study analyzed plasma FFA concentration in children with and without AO. Twenty-nine children classified with AO were matched by age and sex with 29 non-obese individuals. Blood samples were collected after fasting for 10–12 h. Plasma concentration of glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined by automatized methods. FFAs were analyzed by gas chromatography. Children with and without AO had similar age (7.1 ± 2.6 vs. 7.2 ± 2.7 years; p > 0.05) but obese children showed higher (p < 0.05) body mass index (BMI) (+4.3 kg/m2), systolic blood pressure (+5.1 mmHg), and insulin (+27.8 pmol/L). There were no significant differences in plasma total FFA concentration between groups (1.02 ± 0.61 vs. 0.89 ± 0.37 mmol/L; p > 0.05). However, children with AO had higher palmitoleic acid (0.94 vs. 0.70 wt %; p < 0.05) and dihomo-gamma linoleic acid (DHGL) (2.76 vs. 2.07 wt %; p < 0.05). Palmitoleic and DHGL acids correlated (p < 0.05) with BMI (r = 0.397; r = 0.296, respectively) and with waist circumference (r = 0.380; r = 0.276, respectively). Palmitoleic acid correlated positively with systolic blood pressure (r = 0.386; p < 0.05) and negatively with HDL-C (−0.572; p < 0.01). In summary, children with AO have higher plasmatic concentrations of free palmitoleic and DHGL fatty acids, which correlate with cardiometabolic risk factors. PMID:29301242

  17. Leptin Rapidly Improves Glucose Homeostasis in Obese Mice by Increasing Hypothalamic Insulin Sensitivity

    PubMed Central

    Koch, Christiane; Augustine, Rachael A.; Steger, Juliane; Ganjam, Goutham K.; Benzler, Jonas; Pracht, Corinna; Lowe, Chrishanthi; Schwartz, Michael W.; Shepherd, Peter R.; Anderson, Greg M.; Grattan, David R.; Tups, Alexander

    2013-01-01

    Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. In hyperglycemic, leptin-deficient Lepob/ob mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes. PMID:21123564

  18. Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity.

    PubMed

    Koch, Christiane; Augustine, Rachael A; Steger, Juliane; Ganjam, Goutham K; Benzler, Jonas; Pracht, Corinna; Lowe, Chrishanthi; Schwartz, Michael W; Shepherd, Peter R; Anderson, Greg M; Grattan, David R; Tups, Alexander

    2010-12-01

    Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. In hyperglycemic, leptin-deficient Lep(ob/ob) mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes.

  19. Association between gamma glutamyl transferase and insulin resistance markers in healthy obese children.

    PubMed

    Kaushik, Girdhar Gopal; Sharm, Sonali; Sharma, Reenu; Mittal, Prerna

    2009-10-01

    To study the relationship of gamma glutamyl transferase (GGT) with insulin resistance markers [fasting insulin and Homeostasis Model Assessment of-insulin resistance (HOMA-IR)] and to assess the role of GGT as a determinant of insulin resistance in healthy obese children. Fifty healthy obese children (boys and girls with mean age 9.2 +/- 0.73 and 8.8 +/- 0.74 years) born to diabetic mothers were studied. In all the subjects, anthropometric measurements viz, BMI and body weight were studied. The biochemical parameters analysed in fasting samples of subjects were plasma glucose, plasma insulin, serum GGT and calculation of HOMA-IR. The fifty studied subjects belonged to age group 8 to12 years. The difference in mean age of boys and girls was not significant (p = 0.09). Body weight values in all subjects ranged from 20 to 78 kgs and BMI values ranged from 14.5 to 42.1 Kg/m2. No significant difference was observed between body weight and BMI values when compared between boys and girls. A similar trend was observed in the values of biochemical parameters viz, fasting glucose, fasting insulin and HOMA-IR levels when compared between boys and girls (p = 0.72, p = 0.80, p = 0.59). Serum GGT correlated significantly with age, body weight, BMI, fasting insulin and HOMA-IR levels. HOMA-IR values also showed significant correlation with body weight, BMI, fasting glucose and fasting insulin levels. The association of GGT with fasting insulin and HOMA-IR levels was considerably significant compared to its association with other variables. The serum activity of GGT remained correlated with HOMA-IR even after removing the effect of BMI, weight and age on GGT values. The results showed that GGT is a determinant of HOMA-IR independently of age, BMI and weight. A correlation exists between GGT and insulin resistance markers. The observed correlation indicates that monitoring GGT and fasting insulin levels in obese children might serve to help prevent the development of diabetes in

  20. Association of white and red meat consumption with general and abdominal obesity: a cross-sectional study among a population of Iranian military families in 2016.

    PubMed

    Dabbagh-Moghadam, Arasb; Mozaffari-Khosravi, Hassan; Nasiri, Morteza; Miri, Ali; Rahdar, Maliehe; Sadeghi, Omid

    2017-12-01

    To assess the association of red and white meat consumption with general and abdominal obesity among Iranian military families. In this cross-sectional study, 525 subjects with age range of 19-55 years belong to military families of Army of Islamic Republic of Iran were recruited during 2016. Dietary data were collected using semi-quantitative food-frequency questionnaire. A self-reported questionnaire was used to collect data on demographic characteristics and anthropometric measurements. General obesity was defined as body mass index ≥25 kg/m 2 and abdominal obesity as waist circumference ≥80 cm for women and ≥ 94 cm for men. Finally, we had complete data on 170 subjects for analysis. Mean age of subjects was 33.78 ± 6.48. We found a significant positive association between red meat consumption and abdominal obesity in fully adjusted model, so that subjects in the fourth quartile had 4.51 more odds to be abdominally obese compared with those in the first quartile of red meat consumption (OR 4.51, 95% CI 1.32-15.40). Such relationship was not seen for general obesity. In addition, white meat consumption was not associated with general and abdominal obesity either before or after adjustment for covariates. Red meat consumption was positively associated with abdominal obesity. No significant relationship was found between white meat consumption, and general and abdominal obesity. Therefore, further studies are needed to shed light our findings.

  1. [Contribution of leptin in the development of insulin resistance in pregnant women with obesity].

    PubMed

    Tarasenko, K

    2014-03-01

    The aim of the present study was to investigate contribution of leptin in the development of insulin resistance in obese pregnant women depending on the obesity class as well as its effect on the progression of pregnancy. 36 pregnant women of I and II obesity classes and 21 pregnant women with normal body mass participated in the study. Concentrations of insulin, leptin and C-reactive protein in blood serum were measured with immunoenzymatic assays. Insulin resistance (IR) was determined with the Caro index. Contribution of leptin to development of IR was assessed with the ratio "leptin/Caro index". An increase of leptin concentration in blood serum was found in pregnant women with obesity compared to healthy controls. Moreover, the ratio "leptin/Caro index" increased with IR progression and reached maximum in the group with obesity class II, where it was 5.8 times higher than in the control group. An increased frequency of gestoses and placentary dysfunction were manifestations of weakening of adaptive mechanisms of the organism associated with the IR progression and increased role of leptin in its development. Therefore, activation of adipocyte function through the increased leptin secretion and increased ratio "leptin/Caro index" reflects the important role of leptin in pathogenesis of IR in pregnant women with obesity.

  2. Insulin response in individual tissues of control and gold thioglucose-obese mice in vivo with (1-/sup 14/C)2-deoxyglucose

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cooney, G.J.; Astbury, L.D.; Williams, P.F.

    The dose-response characteristics of several glucose-utilizing tissues (brain, heart, white adipose tissue, brown adipose tissue, and quadriceps muscle) to a single injection of insulin have been compared in control mice and mice made obese with a single injection of gold thioglucose (GTG). Tissue content of (1-/sup 14/C)2-deoxyglucose 6-phosphate and blood disappearance rate of (1-/sup 14/C)2-deoxyglucose (2-DG) were measured at nine different insulin doses and used to calculate rates of 2-DG uptake and phosphorylation in tissues from control and obese mice. The insulin sensitivity of tissues reflected in the ED50 of insulin response varied widely, and brown adipose tissue was themore » most insulin-sensitive tissue studied. In GTG-obese mice, heart, quadriceps, and brown adipose tissue were insulin resistant (demonstrated by increased ED50), whereas in white adipose tissue, 2-DG phosphorylation was more sensitive to insulin. Brain 2-DG phosphorylation was insulin independent in control and obese animals. The largest decrease in insulin sensitivity in GTG-obese mice was observed in brown adipose tissue. The loss of diet-induced thermogenesis in brown adipose tissue as a result of the hypothalamic lesion in GTG-obese mice could be a major cause of insulin resistance in brown adipose tissue. Because brown adipose tissue can make a major contribution to whole-body glucose utilization, insulin resistance in this tissue may have a significant effect on whole-animal glucose homeostasis in GTG-obese mice.« less

  3. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue.

    PubMed

    Matsubara, Toshiya; Mita, Ayako; Minami, Kohtaro; Hosooka, Tetsuya; Kitazawa, Sohei; Takahashi, Kenichi; Tamori, Yoshikazu; Yokoi, Norihide; Watanabe, Makoto; Matsuo, Ei-Ichi; Nishimura, Osamu; Seino, Susumu

    2012-01-04

    Adipose tissue secretes adipokines that mediate insulin resistance, a characteristic feature of obesity and type 2 diabetes. By differential proteome analysis of cellular models of insulin resistance, we identified progranulin (PGRN) as an adipokine induced by TNF-α and dexamethasone. PGRN in blood and adipose tissues was markedly increased in obese mouse models and was normalized with treatment of pioglitazone, an insulin-sensitizing agent. Ablation of PGRN (Grn(-/-)) prevented mice from high fat diet (HFD)-induced insulin resistance, adipocyte hypertrophy, and obesity. Grn deficiency blocked elevation of IL-6, an inflammatory cytokine, induced by HFD in blood and adipose tissues. Insulin resistance induced by chronic administration of PGRN was suppressed by neutralizing IL-6 in vivo. Thus, PGRN is a key adipokine that mediates HFD-induced insulin resistance and obesity through production of IL-6 in adipose tissue, and may be a promising therapeutic target for obesity. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Vitamin D deficiency in childhood obesity is associated with high levels of circulating inflammatory mediators, and low insulin sensitivity.

    PubMed

    Reyman, M; Verrijn Stuart, A A; van Summeren, M; Rakhshandehroo, M; Nuboer, R; de Boer, F K; van den Ham, H J; Kalkhoven, E; Prakken, B; Schipper, H S

    2014-01-01

    Childhood obesity is accompanied by low-grade systemic inflammation, which contributes to the development of insulin resistance and cardiovascular complications later in life. As vitamin D exhibits profound immunomodulatory functions and vitamin D deficiency is highly prevalent in childhood obesity, we hypothesized that vitamin D deficiency in childhood obesity coincides with enhanced systemic inflammation and reduced insulin sensitivity. In a cross-sectional study of 64 obese and 32 healthy children aged 6-16 years, comprehensive profiling of 32 circulating inflammatory mediators was performed, together with assessment of 25-hydroxyvitamin D (25(OH)D) levels and measures for insulin sensitivity. Severe vitamin D insufficiency, which is further referred to as vitamin D deficiency, was defined as a 25(OH)D level ≤37.5 nmol l(-1), and was highly prevalent in obese (56%) versus healthy control children (16%). Throughout the study, 25(OH)D-deficient children were compared with the other children, including 25(OH)D insufficient (37.5-50 nmol l(-1)) and 25(OH)D sufficient children (≥50 nmol l(-1)). First, 25(OH)D-deficient obese children showed a lower insulin sensitivity than other obese children, as measured by a lower quantitative insulin sensitivity check index. Second, the association between 25(OH)D deficiency and insulin resistance in childhood obesity was confirmed with multiple regression analysis. Third, 25(OH)D-deficient obese children showed higher levels of the inflammatory mediators cathepsin S, chemerin and soluble vascular adhesion molecule (sVCAM), compared with the other obese children. Finally, hierarchical cluster analysis revealed an over-representation of 25(OH)D deficiency in obese children expressing inflammatory mediator clusters with high levels of cathepsin S, sVCAM and chemerin. 25(OH)D deficiency in childhood obesity was associated with enhanced systemic inflammation and reduced insulin sensitivity. The high cathepsin S and sVCAM levels

  5. Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats.

    PubMed

    Potikanond, Saranyapin; Rattanachote, Pinyada; Pintana, Hiranya; Suntornsaratoon, Panan; Charoenphandhu, Narattaphol; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2016-02-01

    The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, n=12) or a sham operation (S, n=12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham-operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats. © 2016 Society for Endocrinology.

  6. Comparison of β-cell dysfunction and insulin resistance correlating obesity with type 2 diabetes: A cross-sectional study.

    PubMed

    Liu, Jia; Wang, Ying; Hu, Yanjin; Leng, Song; Wang, Guang

    2016-07-01

    To assess the contribution of β-cell dysfunction and insulin resistance to type 2 diabetes (T2D) in obese and non-obese Chinese people. In this cross-sectional study, we recruited 1384 newly diagnosed T2D patients and 1712 healthy controls. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). β-cell function was estimated by homeostasis model assessment of β-cell function (HOMA-β) and 60min insulinogenic index (IGI60). We compared the insulin resistance and β-cell function of obese and non-obese Chinese patients with and without T2D. 50.18% of control participants and 62.28% of T2D patients were obese (BMI≥25kg/m(2)). HOMA-IR, HOMA-β and IGI60 were significantly higher in obese than non-obese, irrespective of T2D. Non-obese T2D patients had significantly greater HOMA-IR, and lower HOMA-β and IGI60 than non-obese control participants. The obese T2D group had lower HOMA-β and IGI60 than the obese control group. There was no significant difference in HOMA-IR between the obese T2D and obese control groups. Multivariate logistic regression analysis revealed that HOMA-IR was associated with T2D only in non-obese group, and HOMA-β and IGI60 were associated with T2D in both non-obese and obese groups. HOMA-β and IGI60 were associated with T2D in obese and non-obese patients, but HOMA-IR was associated with T2D in non-obese Chinese. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial

    PubMed Central

    Tarnow, Lise; Frandsen, Merete; Nielsen, Bente B; Hansen, Birgitte V; Pedersen, Oluf; Parving, Hans-Henrik; Vaag, Allan A

    2009-01-01

    Objectives To study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes. Design Randomised, double blind, double dummy, parallel trial. Setting Secondary care in Denmark between 2003 and 2006. Participants Non-obese patients (BMI ≤27) with preserved beta cell function. Interventions After a four month run-in period with repaglinide plus metformin combination therapy, patients with a glycated haemoglobin (HbA1c) concentration of 6.5% or more were randomised to repaglinide 6 mg or metformin 2000 mg. All patients also received biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units once a day before dinner for 12 months. Insulin dose was adjusted aiming for a fasting plasma glucose concentration of 4.0-6.0 mmol/l. The target of HbA1c concentration was less than 6.5%. Treatment was intensified to two or three insulin injections a day if glycaemic targets were not reached. Main outcome measure HbA1c concentration. Results Of the 459 patients who were eligible, 102 were randomised, and 97 completed the trial. Patients had had type 2 diabetes for approximately 10 years. At the end of treatment, HbA1c concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA1c 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P=0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments −2.51 kg, 95% confidence interval −4.07 to −0.95). Conclusions In non-obese patients with type 2 diabetes and poor glycaemic regulation on oral hypoglycaemic agents, overall glycaemic regulation with

  8. Greater physical activity levels during pregnancy are associated with lower inflammation and insulin resistance in obese women

    USDA-ARS?s Scientific Manuscript database

    Compared to lean pregnant women, obese women develop greater insulin resistance and systemic inflammation during pregnancy. Identifying lifestyle factors that can reduce the metabolic effect of obesity during pregnancy is critical to protect both the mother and the fetus from insulin resistance and ...

  9. Failure to initiate early insulin therapy - A risk factor for diabetic retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report number 35).

    PubMed

    Gupta, Aditi; Delhiwala, Kushal S; Raman, Rajiv P G; Sharma, Tarun; Srinivasan, Sangeetha; Kulothungan, Vaitheeswaran

    2016-06-01

    Insulin users have been reported to have a higher incidence of diabetic retinopathy (DR). The aim was to elucidate the factors associated with DR among insulin users, especially association between duration, prior to initiating insulin for Type 2 diabetes mellitus (DM) and developing DR. Retrospective cross-sectional observational study included 1414 subjects having Type 2 DM. Insulin users were defined as subjects using insulin for glycemic control, and insulin nonusers as those either not using any antidiabetic treatment or using diet control or oral medications. The duration before initiating insulin after diagnosis was calculated by subtracting the duration of insulin usage from the duration of DM. DR was clinically graded using Klein's classification. SPSS (version 9.0) was used for statistical analysis. Insulin users had more incidence of DR (52.9% vs. 16.3%, P < 0.0001) and sight threatening DR (19.1% vs. 2.4%, P < 0.0001) in comparison to insulin nonusers. Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00-1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02-1.29, P = 0.021) was associated with DR. The presence of DR was significantly associated with longer duration (≥5 years) prior to initiating insulin therapy, overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic control (32.5% vs. 67.5%, P = 0.022). The presence of DR is significantly associated with longer duration of diabetes (>5 years) and sub-optimal glycemic control (glycosylated hemoglobin <7.0%). Among insulin users, abdominal obesity was found to be a significant predictor of DR; DR is associated with longer duration prior to initiating insulin therapy in Type 2 DM subjects with suboptimal glycemic control.

  10. Adipocytokines, neuropeptide Y and insulin resistance in overweight women with gynoid and android type of adipose tissue distribution.

    PubMed

    Orbetzova, Maria M; Koleva, Daniela I; Mitkov, Mitko D; Atanassova, Iliana B; Nikolova, Julia G; Atanassova, Pepa K; Genchev, Gencho D

    2012-01-01

    The AIM of the study was to compare the levels of certain adipose tissue hormones in women with the two main morphological types of obesity - android and gynoid obesity. The study included 2 groups of age- and weight-matched women with android (n = 32) and gynoid (n = 27) type of obesity, and a group of age-matched healthy women (n = 24) with normal weight and body constitution. Leptin, resistin, tumour necrosis factor alpha (TNFalpha), neuropeptide Y (NPY), glucose and insulin were measured. HOMA index was calculated. Leptin levels in the women with gynoid obesity did not differ significantly from those in the controls and the women with android obesity. The controls had significantly lower leptin levels compared with the android obesity women. NPY was significantly higher in the control women compared to the women with android obesity and did not differ significantly between the two groups of obese women. TNFalpha levels in all groups were very similar. Resistin did not show significant differences between all groups but tended to have the lowest levels in the controls. In the women with android obesity, insulin was significantly higher than that in the women with gynoid obesity and the controls. Insulin resistance was found in the women with android obesity only. Basal insulin and HOMA index in the women with gynoid obesity did not differ significantly from the values in the control group. The results from this study contribute to understanding the association of adipose tissue hormones and insulin resistance in obesity. When adipose tissue is predominantly distributed in the abdominal area at similar amount and percentage of body fats, leptin production is higher and insulin resistance develops. In the gynoid type of adipose tissue predisposition, overt insulin resistance is not found, leptin levels does not differ significantly from those in the control group.

  11. Metabolic syndrome in overweight and obese Japanese children.

    PubMed

    Yoshinaga, Masao; Tanaka, Satoru; Shimago, Atsushi; Sameshima, Koji; Nishi, Junichiro; Nomura, Yuichi; Kawano, Yoshifumi; Hashiguchi, Jun; Ichiki, Takeo; Shimizu, Shinichiro

    2005-07-01

    To determine the prevalence of and sex differences related to the metabolic syndrome among obese and overweight elementary school children. Subjects were 471 overweight or obese Japanese children. Children meeting at least three of the following five criteria qualified as having the metabolic syndrome: abdominal obesity, elevated blood pressure, low high-density lipoprotein-cholesterol levels, high triglyceride levels, and high fasting glucose levels. Fasting insulin levels were also examined. Japanese obese children were found to have a significantly lower prevalence (17.7%) of the metabolic syndrome than U.S. obese adolescents (28.7%, p = 0.0014). However, Japanese overweight children had a similar incidence (8.7%) of the metabolic syndrome compared with U.S. overweight adolescents (6.8%). Hyperinsulinemia in girls and abdominal obesity in boys are characteristic features of individual metabolic syndrome factors in Japanese children. The prevalence of the metabolic syndrome is not lower in preteen Japanese overweight children than in U.S. overweight adolescents, although it is significantly lower in Japanese obese preteen children than in U.S. obese adolescents. Primary and secondary interventions are needed for overweight preteen children in Japan.

  12. Insulin-induced capillary recruitment is impaired in both lean and obese women with PCOS.

    PubMed

    Ketel, I J G; Serné, E H; Ijzerman, R G; Korsen, T J M; Twisk, J W; Hompes, P G A; Smulders, Y M; Homburg, R; Vorstermans, L; Stehouwer, C D A; Lambalk, C B

    2011-11-01

    Insulin resistance, i.e. impaired insulin-mediated glucose uptake (IMGU), is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). Insulin-induced capillary recruitment (IICR) is considered a significant determinant of IMGU. We investigated whether IICR is a determinant IMGU in obese and lean women with and without PCOS. The study included 36 women with PCOS (20 lean, BMI 21.9 ± 2.3 kg/m(2) and 16 obese, BMI 35.9 ± 6.0 kg/m(2)) and 27 age-matched healthy controls (14 lean, BMI 22.2 ± 1.8 kg/m(2) and 13 obese, BMI 40.5 ± 7.0 kg/m(2)). IICR was evaluated by capillary microscopy during an isoglycemic-hyperinsulinemic clamp. IMGU was expressed as M/I value. The M/I value was significantly lower in obese PCOS women compared with obese controls [0.5 (0.2-1.1) versus 0.8 (0.3-1.4) (mg kg(-1) min(-1) pmol l(-1)) × 100, P < 0.01], whereas the small difference between lean PCOS and lean control women was non-significant [1.5 (0.5-2.6) versus 1.7 (1.0-3.7) (mg kg(-1) min(-1) pmol l(-1)) × 100, P = 0.17]. Hyperinsulinemia increased capillary recruitment in lean controls (53.5 ± 20.3 versus 64.9 ± 27.4 n/mm(2), P < 0.05), but not in either PCOS group nor in obese controls. IICR and androgens were a determinant of M/I value only in lean women with or without PCOS. PCOS per se is associated with impaired IICR. Obese women with PCOS, in part independent of obesity, demonstrated a profound insulin resistance, whereas the difference between lean PCOS women and healthy controls was small and statistically non-significant. IICR was a determinant of IMGU in lean, but not in obese, women regardless of the presence of PCOS.

  13. Predictive equations for central obesity via anthropometrics, stereovision imaging and MRI in adults.

    PubMed

    Lee, Jane J; Freeland-Graves, Jeanne H; Pepper, M Reese; Yao, Ming; Xu, Bugao

    2014-03-01

    Abdominal visceral adiposity is related to risks for insulin resistance and metabolic perturbations. Magnetic resonance imaging (MRI) and computed tomography are advanced instruments that quantify abdominal adiposity; yet field use is constrained by their bulkiness and costliness. The purpose of this study is to develop prediction equations for total abdominal, subcutaneous, and visceral adiposity via anthropometrics, stereovision body imaging (SBI), and MRI. Participants (67 men and 55 women) were measured for anthropometrics and abdominal adiposity volumes evaluated by MRI umbilicus scans. Body circumferences and central obesity were obtained via SBI. Prediction models were developed via multiple linear regression analysis, utilizing body measurements and demographics as independent predictors, and abdominal adiposity as a dependent variable. Cross-validation was performed by the data-splitting method. The final total abdominal adiposity prediction equation was -470.28 + 7.10 waist circumference - 91.01 gender + 5.74 sagittal diameter (R2 = 89.9%), subcutaneous adiposity was -172.37 + 8.57 waist circumference - 62.65 gender - 450.16 stereovision waist-to-hip ratio (R2 =90.4%), and visceral adiposity was -96.76 + 11.48 central obesity depth - 5.09 central obesity width + 204.74 stereovision waist-to-hip ratio - 18.59 gender (R2 = 71.7%). R2 significantly improved for predicting visceral fat when SBI variables were included, but not for total abdominal or subcutaneous adiposity. SBI is effective for predicting visceral adiposity and the prediction equations derived from SBI measurements can assess obesity. Copyright © 2013 The Obesity Society.

  14. Vitamin D insufficiency is associated with insulin resistance independently of obesity in primary schoolchildren. The healthy growth study.

    PubMed

    Moschonis, George; Androutsos, Odysseas; Hulshof, Toine; Dracopoulou, Maria; Chrousos, George P; Manios, Yannis

    2018-04-02

    To explore the associations of vitamin D status and obesity with insulin resistance (IR) in children. A sample of 2282 schoolchildren (9-13 years old) in Greece was examined. Sociodemographic, anthropometric (weight, height), biochemical (fasting plasma glucose, serum insulin and 25(OH)D), pubertal status and physical activity data were collected, using standard methods. The "Vitamin D Standardization Program" protocol was applied to standardize serum 25(OH)D values. The prevalence of vitamin D insufficiency (serum 25(OH)D < 50 nmol/L) was higher in obese children compared to their over- and normal-weight counterparts (60.5% vs 51.6% and 51%, P = .017). Furthermore, children with IR (both obese and non-obese) had higher prevalence of vitamin D insufficiency compared to non-obese, non-insulin resistant children (66% and 59.2% vs 49.8%, P < .05), possibly indicating that IR is associated with vitamin D insufficiency, independently of obesity. In line with the above, the results from logistic regression analyses controlled for several potential confounders, showed a 1.48 (95% C.I: 1.2-1.84) higher likelihood for vitamin D insufficiency for insulin resistant children compared to the non-insulin resistant ones, while no significant association was observed with obesity. The present study revealed a high prevalence of vitamin D insufficiency among schoolchildren in Greece, particularly among obese and insulin resistant ones. In addition, it highlighted that the significant association of vitamin D insufficiency with IR is possibly independent of obesity. Further clinical trials are needed to confirm this possible independent association but also explore the potential beneficial effect of vitamin D supplementation on IR and possibly on weight management too. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients.

    PubMed

    Jazet, I M; Schaart, G; Gastaldelli, A; Ferrannini, E; Hesselink, M K; Schrauwen, P; Romijn, J A; Maassen, J A; Pijl, H; Ouwens, D M; Meinders, A E

    2008-02-01

    Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with substantial weight loss has not been fully elucidated. The aim of this study was to investigate the effect of loss of 50% of excess weight [50% excess weight reduction (EWR)] on EGP, whole-body insulin sensitivity and the disturbed myocellular insulin-signalling pathway in ten obese insulin-treated type 2 diabetic patients. A euglycaemic-hyperinsulinaemic clamp with stable isotopes ([6,6-(2)H2]glucose and [2H5]glycerol) combined with skeletal muscle biopsies was performed during a very low energy diet (VLED; 1,883 kJ/day) on day 2 and again after 50% EWR. Oral blood glucose-lowering agents and insulin were discontinued 3 weeks prior to the VLED and at the start of the VLED, respectively. Loss of 50% EWR (20.3+/-2.2 kg from day 2 to day of 50% EWR) normalised basal EGP and improved insulin sensitivity, especially insulin-stimulated glucose disposal (18.8+/-2.0 to 39.1+/-2.8 micromol kg fat-free mass(-1) min(-1), p=0.001). The latter was accompanied by improved insulin signalling at the level of the recently discovered protein kinase B/Akt substrates AS160 and PRAS40 along with a decrease in intramyocellular lipid (IMCL) content. Considerable weight loss in obese, insulin-treated type 2 diabetic patients normalises basal EGP and improves insulin sensitivity resulting from an improvement in insulin signal transduction in skeletal muscle. The decrease in IMCL might contribute to this effect.

  16. DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance.

    PubMed

    García-Cardona, M C; Huang, F; García-Vivas, J M; López-Camarillo, C; Del Río Navarro, B E; Navarro Olivos, E; Hong-Chong, E; Bolaños-Jiménez, F; Marchat, L A

    2014-11-01

    Epigenetic alterations have been suggested to be associated with obesity and related metabolic disorders. Here we examined the correlation between obesity and insulin resistance with the methylation frequency of the leptin (LEP) and adiponectin (ADIPOQ) promoters in obese adolescents with the aim to identify epigenetic markers that might be used as tools to predict and follow up the physiological alterations associated with the development of the metabolic syndrome. One hundred and six adolescents were recruited and classified according to body mass index and homeostasis model of assessment-insulin resistance index. The circulating concentrations of leptin, adiponectin and of several metabolic markers of obesity and insulin resistance were determined by standard methods. The methylation frequency of the LEP and ADIPOQ promoters was determined by methylation-specific PCR (MS-PCR) in DNA obtained from peripheral blood samples. Obese adolescents without insulin resistance showed higher and lower circulating levels of, respectively, leptin and adiponectin along with increased plasmatic concentrations of insulin and triglycerides. They also exhibited the same methylation frequency than lean subjects of the CpG sites located at -51 and -31 nt relative to the transcription start site of the LEP gene. However, the methylation frequency of these nucleotides dropped markedly in obese adolescents with insulin resistance. We found the same inverse relationship between the combined presence of obesity and insulin resistance and the methylation frequency of the CpG site located at -283 nt relative to the start site of the ADIPOQ promoter. These observations sustain the hypothesis that epigenetic modifications might underpin the development of obesity and related metabolic disorders. They also validate the use of blood leukocytes and MS-PCR as a reliable and affordable methodology for the identification of epigenetic modifications that could be used as molecular markers to

  17. Socio-Demographic and Dietary Factors Associated with Excess Body Weight and Abdominal Obesity among Resettled Bhutanese Refugee Women in Northeast Ohio, United States

    PubMed Central

    Bhatta, Madhav P.; Assad, Lori; Shakya, Sunita

    2014-01-01

    Studies of obesity and related health conditions among the Bhutanese, one of the largest refugee groups resettled in the United States in the past five years, are limited. This study examined the factors associated with excess body weight (body mass index ≥ 23 kg/m2) and abdominal obesity (waist circumference > 80 cm) in a community-based sample of 18–65 year old Bhutanese refugee women in Northeast Ohio. A Nepali-language questionnaire was used to measure socio-demographic and dietary factors. Height, weight, and waist circumference were measured to define excess body weight and abdominal obesity. The mean (±standard deviation) age of the 108 participants was 36.5 (±12.2) years and length of time in the U.S. was 19.4 (±11.9) months. Overall, 64.8% and 69.4% of the women had excess body weight and abdominal obesity, respectively. Age was significantly associated with both excess body weight (odds ratio: 1.10; 95% confidence interval: 1.05–1.16) and abdominal obesity (1.09; 1.04–1.14). Consuming meat (4.01; 1.14–14.60) was significantly associated with excess body weight but not abdominal obesity. These findings suggest the need for lifestyle and dietary change education programs among this new and vulnerable group to reduce the prevalence of excess body weight and abdominal obesity and their health consequences. PMID:24968209

  18. Glucose-6-Phosphate Dehydrogenase Deficiency Improves Insulin Resistance With Reduced Adipose Tissue Inflammation in Obesity.

    PubMed

    Ham, Mira; Choe, Sung Sik; Shin, Kyung Cheul; Choi, Goun; Kim, Ji-Won; Noh, Jung-Ran; Kim, Yong-Hoon; Ryu, Je-Won; Yoon, Kun-Ho; Lee, Chul-Ho; Kim, Jae Bum

    2016-09-01

    Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PD(mut) mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses. © 2016 by the American Diabetes Association.

  19. Interactive relations of type 2 diabetes and abdominal obesity to cognitive impairment: A cross-sectional study in rural area of Xi'an in China.

    PubMed

    Li, Yanbo; Shang, Suhang; Fei, Yulang; Chen, Chen; Jiang, Yu; Dang, Liangjun; Liu, Jie; Ma, Louyan; Wei, Meng; Qu, Qiumin

    2018-01-01

    Type 2 diabetes and obesity, which are frequently comorbid, have been associated with cognitive impairment. We aim to examine the potential modulating effect between obesity and diabetes on cognitive impairment. We recruited 865 adults (aged ≥55years) lived in a village of Xi'an in China from October 2014 to March 2015. All participants underwent biomedical and neuropsychological assessment. Relations of diabetes and abdominal obesity to cognitive impairment were examined in multiple regression models. A total of 155 participants (17.9%) presented with the diagnosis of cognitive impairment. Diabetes or obesity alone wasn't significantly associated with cognitive impairment. Interaction analysis showed a significant interaction between abdominal obesity and diabetes on cognitive impairment. Stratified multivariate analysis revealed that the association between diabetes and cognitive impairment was positive in participants with abdominal obesity (OR 2.436, 95% CI 1.345-4.411, p=0.003, in diabetics with high WC, and OR 2.348, 95% CI 1.373-4.014, p=0.002, in diabetics with high WHR), but negative in those without abdominal obesity. Type 2 diabetes interacts with abdominal obesity to be associated with an increased risk of cognitive impairment by more than two times. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Lysophosphatidic acid impairs glucose homeostasis and inhibits insulin secretion in high-fat diet obese mice.

    PubMed

    Rancoule, C; Attané, C; Grès, S; Fournel, A; Dusaulcy, R; Bertrand, C; Vinel, C; Tréguer, K; Prentki, M; Valet, P; Saulnier-Blache, J S

    2013-06-01

    Lysophosphatidic acid (LPA) is a lipid mediator produced by adipocytes that acts via specific G-protein-coupled receptors; its synthesis is modulated in obesity. We previously reported that reducing adipocyte LPA production in high-fat diet (HFD)-fed obese mice is associated with improved glucose tolerance, suggesting a negative impact of LPA on glucose homeostasis. Here, our aim was to test this hypothesis. First, glucose tolerance and plasma insulin were assessed after acute (30 min) injection of LPA (50 mg/kg) or of the LPA1/LPA3 receptor antagonist Ki16425 (5 mg kg(-1) day(-1), i.p.) in non-obese mice fed a normal diet (ND) and in obese/prediabetic (defined as glucose-intolerant) HFD mice. Glucose and insulin tolerance, pancreas morphology, glycogen storage, glucose oxidation and glucose transport were then studied after chronic treatment (3 weeks) of HFD mice with Ki16425. In ND and HFD mice, LPA acutely impaired glucose tolerance by inhibiting glucose-induced insulin secretion. These effects were blocked by pre-injection of Ki16425 (5 mg/kg, i.p.). Inhibition of glucose-induced insulin secretion by LPA also occurred in isolated mouse islets. Plasma LPA was higher in HFD mice than in ND mice and Ki16425 transiently improved glucose tolerance. The beneficial effect of Ki16425 became permanent after chronic treatment and was associated with increased pancreatic islet mass and higher fasting insulinaemia. Chronic treatment with Ki16425 also improved insulin tolerance and increased liver glycogen storage and basal glucose use in skeletal muscle. Exogenous and endogenous LPA exerts a deleterious effect on glucose disposal through a reduction of plasma insulin; pharmacological blockade of LPA receptors improves glucose homeostasis in obese/prediabetic mice.

  1. Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men.

    PubMed

    Pincelli, A I; Brunani, A; Caumo, A; Scacchi, M; Pasqualinotto, L; Tibaldi, A; Dubini, A; Bonadonna, S; Cavagnini, F

    2001-01-01

    The negative-feedback control exerted by plasma insulin on beta-cell insulin release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-hour fast during the procedure. We elected to elucidate the role of physiologic hyperinsulinemia per se in the insulin negative autofeedback in obese men. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body mass index [BMI], 41 +/- 1.15 kg/m2) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m2) underwent 2 studies in random order: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusion rate of 1 mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05). Exogenous insulin infusion significantly suppressed serum C-peptide at steady state ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 vbaseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-peptide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, and 1.96 +/- 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not superior to a 2.5-hour fast for the suppression of beta-cell activity, suggesting an impairment of the insulin negative autofeedback in this clinical condition.

  2. Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance.

    PubMed

    Palanivel, R; Fullerton, M D; Galic, S; Honeyman, J; Hewitt, K A; Jorgensen, S B; Steinberg, G R

    2012-11-01

    Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known. We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed. The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic-euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1). These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity.

  3. Activation and regulation of the pattern recognition receptors in obesity-induced adipose tissue inflammation and insulin resistance.

    PubMed

    Watanabe, Yasuharu; Nagai, Yoshinori; Takatsu, Kiyoshi

    2013-09-23

    Obesity-associated chronic tissue inflammation is a key contributing factor to type 2 diabetes mellitus, and a number of studies have clearly demonstrated that the immune system and metabolism are highly integrated. Recent advances in deciphering the various immune cells and signaling networks that link the immune and metabolic systems have contributed to our understanding of the pathogenesis of obesity-associated inflammation. Other recent studies have suggested that pattern recognition receptors in the innate immune system recognize various kinds of endogenous and exogenous ligands, and have a crucial role in initiating or promoting obesity-associated chronic inflammation. Importantly, these mediators act on insulin target cells or on insulin-producing cells impairing insulin sensitivity and its secretion. Here, we discuss how various pattern recognition receptors in the immune system underlie the etiology of obesity-associated inflammation and insulin resistance, with a particular focus on the TLR (Toll-like receptor) family protein Radioprotective 105 (RP105)/myeloid differentiation protein-1 (MD-1).

  4. Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men.

    PubMed

    Jocken, J W E; Goossens, G H; van Hees, A M J; Frayn, K N; van Baak, M; Stegen, J; Pakbiers, M T W; Saris, W H M; Blaak, E E

    2008-02-01

    Obesity is characterised by increased triacylglycerol storage in adipose tissue. There is in vitro evidence for a blunted beta-adrenergically mediated lipolytic response in abdominal subcutaneous adipose tissue (SAT) of obese individuals and evidence for this at the whole-body level in vivo. We hypothesised that the beta-adrenergically mediated effect on lipolysis in abdominal SAT is also impaired in vivo in obese humans. We investigated whole-body and abdominal SAT glycerol metabolism in vivo during 3 h and 6 h [2H5]glycerol infusions. Arterio-venous concentration differences were measured in 13 lean and ten obese men after an overnight fast and during intravenous infusion of the non-selective beta-adrenergic agonist isoprenaline [20 ng (kg fat free mass)(-1) min(-1)]. Lean and obese participants showed comparable fasting glycerol uptake by SAT (9.7+/-3.4 vs 9.3+/-2.5% of total release, p=0.92). Furthermore, obese participants showed an increased whole-body beta-adrenergically mediated lipolytic response versus lean participants. However, their fasting lipolysis was blunted [glycerol rate of appearance: 7.3+/-0.6 vs 13.1+/-0.9 micromol (kg fat mass)(-1) min(-1), p<0.01], as was the beta-adrenergically mediated lipolytic response per unit SAT [Delta total glycerol release: 140+/-71 vs 394+/-112 nmol (100 g tissue)(-1) min(-1), p<0.05] compared with lean participants. Net triacylglycerol flux tended to increase in obese compared with lean participants during beta-adrenergic stimulation [Delta net triacylglycerol flux: 75+/-32 vs 16+/-11 nmol (100 g tissue)(-1) min(-1), p=0.06]. We demonstrated in vivo that beta-adrenergically mediated lipolytic response is impaired systematically and in abdominal SAT of obese versus lean men. This may be important in the development or maintenance of increased triacylglycerol stores and obesity.

  5. Central arterial stiffness and diastolic dysfunction are associated with insulin resistance and abdominal obesity in young women but polycystic ovary syndrome does not confer additional risk.

    PubMed

    Rees, E; Coulson, R; Dunstan, F; Evans, W D; Blundell, H L; Luzio, S D; Dunseath, G; Halcox, J P; Fraser, A G; Rees, D A

    2014-09-01

    Are arterial stiffness, carotid intima-media thickness and diastolic dysfunction increased in young women with polycystic ovary syndrome (PCOS) independently of the effects of obesity? Insulin resistance and central obesity are associated with subclinical cardiovascular dysfunction in young women, but a diagnosis of PCOS does not appear to confer additional risk at this age. Some studies have shown that young women with PCOS may have increased measures of cardiovascular risk, including arterial stiffness, carotid intima-media thickness and myocardial dysfunction. However, it is difficult to establish how much of this risk is due to PCOS per se and how much is due to obesity and insulin resistance, which are common in PCOS and themselves associated with greater vascular risk. This cross-sectional study comprised 84 women with PCOS and 95 healthy volunteers, aged 16-45 years. The study was conducted in a university hospital. Subjects underwent a comprehensive assessment of body composition (including computed tomography (CT) assessment of visceral fat; VF), measurements of arterial stiffness (aortic pulse wave velocity; aPWV), common carotid intima-media thickness (ccIMT), diastolic function (longitudinal tissue velocity; e':a') and endocrinological measures. A sample size of 80 in each group gave 80% power for detecting a difference of 0.45 m/s in aPWV or a difference of 0.25 in e':a'. After adjustment for age and body mass index (BMI), PCOS subjects had a greater insulin response (insulin area under the curve-IAUC) following glucose challenge (adjusted difference [AD] 35 900 pmol min/l, P < 0.001) and higher testosterone (AD 0.57 nmol/l, P < 0.001) and high molecular weight adiponectin than controls (AD 3.01 µg/ml, P = 0.02), but no significant differences in aPWV (AD -0.13 m/s, P = 0.33), ccIMT (AD -0.01 mm, P = 0.13), or e':a' (AD -0.01, P = 0.86) were observed. After adjustment for age, height and central pulse pressure, e':a' and aPWV were associated with log

  6. The Roles of IL-6, IL-10, and IL-1RA in Obesity and Insulin Resistance in African-Americans

    PubMed Central

    Doumatey, Ayo; Huang, Hanxia; Zhou, Jie; Chen, Guanjie; Shriner, Daniel; Adeyemo, Adebowale

    2011-01-01

    Objective: The aim of the study was to investigate the associations between IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, measures of obesity, and insulin resistance in African-Americans. Research Design and Methods: Nondiabetic participants (n = 1025) of the Howard University Family Study were investigated for associations between serum IL (IL-1RA, IL-6, IL-10), measures of obesity, and insulin resistance, with adjustment for age and sex. Measures of obesity included body mass index, waist circumference, hip circumference, waist-to-hip ratio, and percent fat mass. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Data were analyzed with R statistical software using linear regression and likelihood ratio tests. Results: IL-1RA and IL-6 were associated with measures of obesity and insulin resistance, explaining 4–12.7% of the variance observed (P values < 0.001). IL-1RA was bimodally distributed and therefore was analyzed based on grouping those with low vs. high IL-1RA levels. High IL-1RA explained up to 20 and 12% of the variance in measures of obesity and HOMA-IR, respectively. Among the IL, only high IL-1RA improved the fit of models regressing HOMA-IR on measures of obesity. In contrast, all measures of obesity improved the fit of models regressing HOMA-IR on IL. IL-10 was not associated with obesity measures or HOMA-IR. Conclusions: High IL-1RA levels and obesity measures are associated with HOMA-IR in this population-based sample of African-Americans. The results suggest that obesity and increased levels of IL-1RA both contribute to the development of insulin resistance. PMID:21956416

  7. Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

    PubMed

    El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

    2012-09-01

    In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 <11.1 mmol/L), and none with diabetes. Using the continuous glucose monitoring system ( CGMS), IFG was detected in 4 cases, the maximum serum blood glucose (BG : 2h or more after meal) was >7.8 and <11.1 mmol/L (IGT) in 9 children (69%) and >11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of <2.7 mmol/L (hypoglycemia). No glycemic abnormality was detected using HbA1C (5.7 ± 0.3%). 11/13 patients had HOMA values >2.6 and QUICKI values <0.35 denoting insulin resistance. Beta cell mass percent (B %) = 200 ± 94.8% and insulin sensitivity values (IS)=50.4 ± 45.5% denoted insulin resistance with hyper-insulinaemia and preserved beta cell mass. In obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

  8. Abrogating Monoacylglycerol Acyltransferase Activity in Liver Improves Glucose Tolerance and Hepatic Insulin Signaling in Obese Mice

    PubMed Central

    Soufi, Nisreen; Chambers, Kari T.; Chen, Zhouji; Schweitzer, George G.; McCommis, Kyle S.; Erion, Derek M.; Graham, Mark J.; Su, Xiong; Finck, Brian N.

    2014-01-01

    Monoacylglycerol acyltransferase (MGAT) enzymes convert monoacylglycerol to diacylglycerol (DAG), a lipid that has been linked to the development of hepatic insulin resistance through activation of protein kinase C (PKC). The expression of genes that encode MGAT enzymes is induced in the livers of insulin-resistant human subjects with nonalcoholic fatty liver disease, but whether MGAT activation is causal of hepatic steatosis or insulin resistance is unknown. We show that the expression of Mogat1, which encodes MGAT1, and MGAT activity are also increased in diet-induced obese (DIO) and ob/obmice. To probe the metabolic effects of MGAT1 in the livers of obese mice, we administered antisense oligonucleotides (ASOs) against Mogat1 to DIO and ob/ob mice for 3 weeks. Knockdown of Mogat1 in liver, which reduced hepatic MGAT activity, did not affect hepatic triacylglycerol content and unexpectedly increased total DAG content. Mogat1 inhibition also increased both membrane and cytosolic compartment DAG levels. However, Mogat1 ASO treatment significantly improved glucose tolerance and hepatic insulin signaling in obese mice. In summary, inactivation of hepatic MGAT activity, which is markedly increased in obese mice, improved glucose tolerance and hepatic insulin signaling independent of changes in body weight, intrahepatic DAG and TAG content, and PKC signaling. PMID:24595352

  9. Laparoscopic sleeve gastrectomy improves body composition and alleviates insulin resistance in obesity related acanthosis nigricans.

    PubMed

    Zhang, Yi; Zhu, Cuiling; Wen, Xin; Wang, Xingchun; Li, Liang; Rampersad, Sharvan; Lu, Liesheng; Zhou, Donglei; Qian, Chunhua; Cui, Ran; Zhang, Manna; Yang, Peng; Qu, Shen; Bu, Le

    2017-11-07

    Acanthosis nigricans (AN) has a close relationship with obesity. It is believed that obesity and AN have the common pathophysiological basis such as hyperinsulinism. This study is aimed to observe the effect of laparoscopic sleeve gastrectomy (LSG) on body composition and insulin resistance in Chinese obese patients with acanthosis nigricans. A total of 37 obese patients who underwent LSG in our hospital were selected for analysis. They were divided into simple obesity (OB n = 14) and obesity with acanthosis nigricans (AN n = 23) group respectively. Body composition was measured by dual-energy X-ray absorptiometry (DEXA). Anthropometric measurements and glucolipid metabolism before and 3 months post LSG were collected for analysis. Patients with AN got noticeable improvement in skin condition and their AN score was significantly decreased (3.52 ± 0.79 vs. 1.48 ± 0.73, P < 0.001).Alleviated insulin resistance and more trunk fat loss than limbs' were observed in both groups (P value < 0.01). In AN group, preoperative android fat mass (FM) was positively correlated with fasting insulin and natural logarithm of HOMA-IR (LNIR) (r = 0.622, 0.608, respectively; all P < 0.01). Besides, changes in android FM and visceral adipose tissue (VAT) also showed significantly positive correlation with changes in LNIR (r = 0.588, r = 0.598, respectively; all P < 0.01). LSG had a positive impact on body composition and skin condition in Chinese obese patients with AN. Loss of android FM and VAT might result in the alleviation of insulin resistance in AN patients. Android fat distribution seems to be a potential indicator of postoperative metabolic benefits for obese patients with AN.

  10. Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects.

    PubMed

    Davison, K; Coates, A M; Buckley, J D; Howe, P R C

    2008-08-01

    Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals. Overweight and obese adults were randomly assigned to high-flavanol cocoa (HF, 902 mg flavanols), HF and exercise, low-flavanol cocoa (LF, 36 mg flavanols), or LF and exercise for 12 weeks (exercise duration was 3 x 45 min per week at 75% of age-predicted maximum heart rate). Body composition was assessed by dual-energy X-ray absorptiometry at 0 and 12 weeks. Brachial artery flow-mediated dilatation (FMD), supine blood pressure (BP) and fasting plasma insulin, and glucose levels were assessed at 0, 6 and 12 weeks, respectively. Insulin sensitivity/resistance was determined using the modified homeostasis model assessment of insulin resistance (HOMA2). A total of 49 subjects (M=18; F=31) completed the intervention. Baseline averages were as follows: body mass index=33.5 kg/m(2); BP=123/76 mm Hg; HOMA2=2.4; FMD=4.3%; rate of fat oxidation during exercise=0.34 g min(-1); abdominal fat=45.7% of total abdominal mass. Compared to LF, HF increased FMD acutely (2 h post-dose) by 2.4% (P<0.01) and chronically (over 12 weeks; P<0.01) by 1.6% and reduced insulin resistance by 0.31% (P<0.05), diastolic BP by 1.6 mm Hg and mean arterial BP by 1.2 mm Hg (P<0.05), independent of exercise. Regular exercise increased fat oxidation during exercise by 0.10 g min(-1) (P<0.01) and reduced abdominal fat by 0.92% (P<0.05). Although HF consumption was shown to improve endothelial function, it did not enhance the effects of exercise on body fat and fat metabolism in obese subjects. However, it may be useful for reducing cardiometabolic risk factors in this population.

  11. Labrador tea (Rhododendron groenlandicum) attenuates insulin resistance in a diet-induced obesity mouse model.

    PubMed

    Ouchfoun, Meriem; Eid, Hoda M; Musallam, Lina; Brault, Antoine; Li, Shilin; Vallerand, Diane; Arnason, John T; Haddad, Pierre S

    2016-04-01

    Using a diet-induced obesity (DIO) mouse model, we investigated the antidiabetic effect of Labrador tea [Rhododendron groenlandicum (Oeder) Kron and Judd], a beverage and medicinal tea used by the Cree Nations of northern Quebec. C57BL6 mice were divided into five groups and given standard chow (~4 % of lipids) or high-fat diet (~35 % of lipids) for 8 weeks until they became obese and insulin resistant. Treatment began by adding the plant extract at three doses (125, 250 and 500 mg/kg) to the high-fat diet for another 8 weeks. At the end of the study, insulin-sensitive tissues (liver, skeletal muscle, adipose tissue) were collected to investigate the plant's molecular mechanisms. Labrador tea significantly reduced blood glucose (13 %), the response to an oral glucose tolerance test (18.2 %) and plasma insulin (65 %) while preventing hepatic steatosis (42 % reduction in hepatic triglyceride levels) in DIO mice. It stimulated insulin-dependent Akt pathway (55 %) and increased the expression of GLUT4 (53 %) in skeletal muscle. In the liver, Labrador tea stimulated the insulin-dependent Akt and the insulin-independent AMP-activated protein kinase pathways. The improvement in hepatic steatosis observed in DIO-treated mice was associated with a reduction in inflammation (through the IKK α/β) and a decrease in the hepatic content of SREBP-1 (39 %). Labrador tea exerts potential antidiabetic action by improving insulin sensitivity and mitigating high-fat diet-induced obesity and hyperglycemia. They validate the safety and efficacy of this plant, a promising candidate for culturally relevant complementary treatment in Cree diabetics.

  12. Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

    PubMed Central

    Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

    2016-01-01

    Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

  13. WNIN/GR-Ob - an insulin-resistant obese rat model from inbred WNIN strain.

    PubMed

    Harishankar, N; Vajreswari, A; Giridharan, N V

    2011-09-01

    WNIN/GR-Ob is a mutant obese rat strain with impaired glucose tolerance (IGT) developed at the National Institute of Nutrition (NIN), Hyderabad, India, from the existing 80 year old Wistar rat (WNIN) stock colony. The data presented here pertain to its obese nature along with IGT trait as evidenced by physical, physiological and biochemical parameters. The study also explains its existence, in three phenotypes: homozygous lean (+/+), heterozygous carrier (+/-) and homozygous obese (-/-). Thirty animals (15 males and 15 females) from each phenotype (+/+, +/-, -/-) and 24 lean and obese (6 males and 6 females) rats were taken for growth and food intake studies respectively. Twelve adult rats from each phenotype were taken for body composition measurement by total body electrical conductivity (TOBEC); 12 rats of both genders from each phenotype at different ages were taken for clinical chemistry parameters. Physiological indices of insulin resistance were calculated according to the homeostasis model assessment for insulin resistance (HOMA-IR) and also by studying U¹⁴C 2-deoxy glucose uptake (2DG). WNINGR-Ob mutants had high growth, hyperphagia, polydipsia, polyurea, glycosuria, and significantly lower lean body mass, higher fat mass as compared with carrier and lean rats. These mutants, at 50 days of age displayed abnormal response to glucose load (IGT), hyperinsulinaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperleptinaemia. Basal and insulin-stimulated glucose uptakes by diaphragm were significantly decreased in obese rats as compared with lean rats. Obese rats of the designated WNIN/GR-Ob strain showed obesity with IGT, as adjudged by physical, physiological and biochemical indices. These indices varied among the three phenotypes, being lowest in lean, highest in obese and intermediate in carrier phenotypes thereby suggesting that obesity is inherited as autosomal incomplete dominant trait in this strain. This mutant obese rat model is easy to

  14. Insulin action and fibrinolysis influenced by vitamin E in obese Type 2 diabetes mellitus.

    PubMed

    Skrha, J; Sindelka, G; Kvasnicka, J; Hilgertová, J

    1999-04-01

    Increased oxidative stress, hypofibrinolysis and insulin resistance are present in obese Type 2 diabetic patients. It is supposed that treatment with antioxidant alpha-tocopherol (vitamin E) could not only decrease free radical production, but also ameliorate insulin action. We evaluated the effect of 3 months administration of vitamin E (600 mg daily) on insulin action examined by hyperinsulinemic clamp in 11 obese Type 2 diabetic patients. Oxidative stress and fibrinolysis were also determined. The administration of vitamin E caused a decrease of glucose disposal rate (26.6 +/- 9.5 vs 21.3 +/- 7.5 micromol/kg/min, P < 0.02) and of metabolic clearance rate of glucose (3.7 +/- 1.6 vs 2.9 +/- 0.8 ml/kg/min. P < 0.02). A decrease of insulin receptor number was observed on erythrocytes after vitamin E (284 +/- 84 vs 171 +/- 59 pmol/l, P < 0.01). Significantly higher plasma malondialdehyde (MDA) concentration documented an increased oxidative stress in diabetic patients as compared with healthy persons (3.13 +/- 0.68 vs 1.89 +/- 0.18 micromol/l, P<0.001). An inverse relationship was found between MDA concentration and insulin sensitivity expressed by glucose disposal rate (r = -0.73). Vitamin E further worsened the hypofibrinolysis documented by a decrease of tissue plasminogen activator (P < 0.01) without changes in its inhibitor PAI-1. In conclusion. our results demonstrate that higher doses of vitamin E may further deteriorate insulin action and fibrinolysis in obese Type 2 diabetic patients.

  15. Inflammasome is a central player in the induction of obesity and insulin resistance

    PubMed Central

    Stienstra, Rinke; van Diepen, Janna A.; Tack, Cees J.; Zaki, Md. Hasan; van de Veerdonk, Frank L.; Perera, Deshani; Neale, Geoffrey A.; Hooiveld, Guido J.; Hijmans, Anneke; Vroegrijk, Irene; van den Berg, Sjoerd; Romijn, Johannes; Rensen, Patrick C. N.; Joosten, Leo A. B.; Netea, Mihai G.; Kanneganti, Thirumala-Devi

    2011-01-01

    Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in proinflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3, resulting in caspase-1 activation and production of proinflammatory cytokines IL-1β and IL-18. Here, we showed that mice deficient in Nlrp3, apoptosis-associated speck-like protein, and caspase-1 were resistant to the development of high-fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Furthermore, hepatic triglyceride content, adipocyte size, and macrophage infiltration in adipose tissue were all reduced in mice deficient in inflammasome components. Monocyte chemoattractant protein (MCP)-1 is a key molecule that mediates macrophage infiltration. Indeed, defective inflammasome activation was associated with reduced MCP-1 production in adipose tissue. Furthermore, plasma leptin and resistin that affect energy use and insulin sensitivity were also changed by inflammasome-deficiency. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance, and suggest inhibition of the inflammasome as a potential therapeutic strategy. PMID:21876127

  16. Does Insulin Explain the Relation between Maternal Obesity and Poor Lactation Outcomes? An Overview of the Literature.

    PubMed

    Nommsen-Rivers, Laurie A

    2016-03-01

    It is well established that obese women are at increased risk of delayed lactogenesis and short breastfeeding duration, but the underlying causal contributors remain unclear. This review summarizes the literature examining the role of insulin in lactation outcomes. Maternal obesity is a strong risk factor for insulin resistance and prediabetes, but until recently a direct role for insulin in milk production had not been elucidated. Over the past 6 y, studies in both animal models and humans have shown insulin-sensitive gene expression to be dramatically upregulated specifically during the lactation cycle. Insulin is now considered to play a direct role in lactation, including essential roles in secretory differentiation, secretory activation, and mature milk production. At the same time, emerging clinical research suggests an important association between suboptimal glucose tolerance and lactation difficulty. To develop effective interventions to support lactation success in obese women further research is needed to identify how, when, and for whom maternal insulin secretion and sensitivity affect lactation ability. © 2016 American Society for Nutrition.

  17. Long-term ingestion of monosodium L-glutamate did not induce obesity, dyslipidemia or insulin resistance: a two-generation study in mice.

    PubMed

    Nakamura, Hidehiro; Kawamata, Yasuko; Kuwahara, Tomomi; Smriga, Miro; Sakai, Ryosei

    2013-01-01

    The use of monosodium glutamate (MSG) as a flavor enhancer spans more than 100 y and there are many studies indicating the safety of general use of MSG. Recently, however, Collison et al. (2010) reported a two-generation study with a low dose of MSG that caused abdominal obesity, insulin resistance and dyslipidemia in mice. Due to public health concerns over metabolic syndrome, their report merits careful analysis. The present study attempted to repeat the Collison et al. findings. Groups of male or female C57BL/6J mice were fed a control diet or one supplemented with high-fructose corn syrup (HFCS) at a level of 20%. Drinking water control was provided or treatment groups were given 0.064% MSG solution (w/v). Diets and MSG administration continued throughout mating and during gestation and lactation periods. To further investigate the effects of ingestion of MSG, the offspring were continued on the same dosing conditions until they reached 32 wk of age. MSG administration in mice fed a normal or a HFCS diet throughout gestation and for 32 wk after birth, did not affect growth, girth size, abdominal fat weight or body composition. This study reports that MSG did not trigger insulin resistance, dyslipidemia or hepatic steatosis, regardless of the diet, not reproducing the results of the above-mentioned study (Collison et al., 2010).

  18. Divergent Effects of a Combined Hormonal Oral Contraceptive on Insulin Sensitivity in Lean versus Obese Women

    PubMed Central

    Cheang, Kai I.; Essah, Paulina A.; Sharma, Susmeeta; Wickham, Edmond P.; Nestler, John E.

    2011-01-01

    Objective To evaluate the effects of a commonly used combined hormonal oral contraceptive (OC) on carbohydrate metabolism in obese as compared with obese women. Design 6-month prospective study. Setting Clinical Research Center at an academic medical center. Patients Premenopausal non-diabetic women with BMI < 25 kg/m2 (n=15) or > 30 kg/m2 (n=14). Intervention Ethinyl estradiol 35mcg and norgestimate 0.18/0.215/0.25 mg for 6 cycles. Main Outcome Measures Insulin sensitivity (Si) by frequent sampling intravenous glucose tolerance test; other indices of insulin sensitivity (ISI HOMA, Matsuda index); fasting lipid panel. Results Si changed from 6.62±3.69 min−1/mu/L (baseline) to 8.23±3.30 min−1/mu/L (6 months) in lean women, and from 4.36±2.32 to 3.82±2.32 min−1/mu/L in obese women (p for interaction=0.0494). Divergent effects on insulin sensitivity were also observed with ISI HOMA (p=0.0128) and Matsuda index (p=0.0227). LDL increased by approximately 20 mg/dL in both groups (p<0.005 [lean]; p<0.01 [obese]). Conclusions Lean and obese women exhibit differential changes in insulin sensitivity when given 6 months of a commonly used OC. The mechanisms of these differences, and whether these divergent effects persist long-term, require further investigations. Capsule Lean and obese non-diabetic women exhibit differential changes in insulin sensitivity when given 6 months of a commonly used OC (ethinyl estradiol 35mcg and norgestimate 0.18/0.215/0.25 mg) PMID:21676394

  19. Glucocorticoid receptor polymorphism in obesity and glucose homeostasis.

    PubMed

    Majer-Łobodzińska, Agnieszka; Adamiec-Mroczek, Joanna

    2017-01-01

    Glucocorticoid receptor (GR) activity plays a significant role in the etiology of obesity and is essential for glucose homeostasis, the development of hyperinsulinaemia and subsequent increased fat deposition. Several polymorphisms in the GR gene have been described, and at least three of them seem to be associated with altered glucocorticoid sensitivity and changes in glucose homeostasis, and other metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to glucocorticoides, increased insulin response to dexamethasone and increased plasma glucose level. BclI polymorphism is associated with increased abdominal obesity, hyperinsulinaemia and increased insulin resistance. Another polymorphism, ER22/23EK, in contrast to the others, is associated with relative resistance to glucocoricides actions and more beneficial metabolic profile-lower insulin resistance level, decreased lower cardiovascular risk and subseuent prolongation of life time. More research is still needed to understand the mechanisms behind these associations at the molecular level.

  20. Does Insulin Explain the Relation between Maternal Obesity and Poor Lactation Outcomes? An Overview of the Literature1234

    PubMed Central

    2016-01-01

    It is well established that obese women are at increased risk of delayed lactogenesis and short breastfeeding duration, but the underlying causal contributors remain unclear. This review summarizes the literature examining the role of insulin in lactation outcomes. Maternal obesity is a strong risk factor for insulin resistance and prediabetes, but until recently a direct role for insulin in milk production had not been elucidated. Over the past 6 y, studies in both animal models and humans have shown insulin-sensitive gene expression to be dramatically upregulated specifically during the lactation cycle. Insulin is now considered to play a direct role in lactation, including essential roles in secretory differentiation, secretory activation, and mature milk production. At the same time, emerging clinical research suggests an important association between suboptimal glucose tolerance and lactation difficulty. To develop effective interventions to support lactation success in obese women further research is needed to identify how, when, and for whom maternal insulin secretion and sensitivity affect lactation ability. PMID:26980825

  1. Adipose Tissue Insulin Resistance in Gestational Diabetes.

    PubMed

    Tumurbaatar, Batbayar; Poole, Aaron T; Olson, Gayle; Makhlouf, Michel; Sallam, Hanaa S; Thukuntla, Shwetha; Kankanala, Sucharitha; Ekhaese, Obos; Gomez, Guillermo; Chandalia, Manisha; Abate, Nicola

    2017-03-01

    Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1. AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose-lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice. We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01-ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P < 0.05 each), (3) AT ENPP1 expression levels were positively correlated with HOMA-IR (P = 0.01-ANOVA). (4) Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046-t test on area under curve [AUC] glucose ). Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.

  2. Population-attributable fraction of hypertension associated with obesity, abdominal obesity, and the joint effect of both in the Central Provinces of Iran.

    PubMed

    Mohammadi, Masoud; Mirzaei, Masoud

    2017-03-01

    The prevalence of obesity has been increasing in Iran over the past decade. This study aimed to determine the population-attributable fraction (PAF) of hypertension associated with obesity, abdominal obesity, and the joint effect of both in the central provinces of Iran. Prevalence of hypertension was extracted from the Iranian Ministry of Health Non-Communicable Disease Risk Factor InfoBase 2009. Measure of association between obesity and hypertension was extracted from Tehran Lipid and Glucose Study, for males and females, in order to calculate the PAF of hypertension associated with obesity. Age standardization of the reported prevalence of obesity was done using the World Health Organization method. The PAF of hypertension associated with the joint effect of obesity and abdominal obesity in females was highest in Semnan Province: 22.7 [95% confidence interval (CI): 4.2-35.6], followed by Qom 21.09 (95% CI: 3.7-33.1), and Yazd 20.3 (95% CI: 3.5-32.1). In males, the highest PAF was observed in Qom Province 31.07 (95% CI: 16.7-41.1), followed by Semnan 29.6 (95% CI: 15.9-39.3), Qazvin 25.9 (95% CI: 13.7-34.5), Tehran 24.2 (95% CI: 12.7-32.3), and Isfahan 20.4 (95% CI: 3.5-27.4). Prevalence of hypertension is higher in more developed provinces. PAFs suggest that a sizable share of hypertension in these provinces is associated with obesity. It is recommended that health promotion programs focus on obesity in the provinces with a higher share of hypertension due to obesity. Copyright © 2016 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  3. Abdominal obesity and its association with socioeconomic factors among adolescents from different living environments.

    PubMed

    Costa de Oliveira Forkert, E; de Moraes, A C F; Carvalho, H B; Kafatos, A; Manios, Y; Sjöström, M; González-Gross, M; Gottrand, F; Beghin, L; Censi, L; Kersting, M; Moreno, L A

    2017-04-01

    Socioeconomic status has been associated with obesity in children and adolescents. This association may be dependent according with where adolescents lives. The aim of this study was to evaluate the association between different socioeconomic indicators such as parental education and occupation and socioeconomic status with abdominal obesity in adolescents from two observational studies: the Healthy Lifestyle in Europe by Nutrition in Adolescence cross-sectional study (HELENA-CSS) and the Brazilian Cardiovascular Adolescent Health (BRACAH) study. European (n = 3192, aged 12.5-17.5 years, with 53.1% girls from HELENA-CSS) and Brazilian (n = 991, aged 14-18 years, with 54.5% girls from BRACAH study) adolescents from two cross-sectional studies were included in this analysis. Complete data on waist circumference (WC), height, socioeconomic status indicators and several confounders were collected. Socioeconomic indicators were measured using a self-reported questionnaire in order to assess the family social status of the adolescents. Multilevel linear regression models were used to examine associations, and results were adjusted for potential confounders. Adjusted results showed inverse associations between mother's and father's education levels (p < 0.001) and father's occupation level (p < 0.001) with waist-to-height ratio (WHtR) and WC in HELENA-CSS girls. Similarly in European girls, socioeconomic indicators by socioeconomic status and maternal occupation level were associated with WHtR. In HELENA-CSS boys, the same significant association was found between WHtR and WC with maternal occupation level. Moreover, in European boys WHtR was also associated with parental education. In Brazilian adolescents, both indicators of abdominal obesity did not remain associated with the independents variables, after adjustment for potential confounders. Abdominal obesity was associated with socioeconomic indicators in higher-income countries, but this

  4. Serum leptin is associated with metabolic syndrome in obese Mexican subjects.

    PubMed

    García-Jiménez, Sara; Bernal Fernández, German; Martínez Salazar, Maria Fernanda; Monroy Noyola, Antonio; Toledano Jaimes, Cairo; Meneses Acosta, Angelica; Gonzalez Maya, Leticia; Aveleyra Ojeda, Elizabeth; Terrazas Meraz, Maria A; Boll, Marie-Catherine; Sánchez-Alemán, Miguel A

    2015-01-01

    The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including insulin resistance, dyslipidemia, high blood pressure, and abdominal adiposity. Obese patients develop leptin resistance, and an increased waist circumference (WC) due to deposition of abdominal fat. The aim of this study was to evaluate the association between circulating leptin levels and MetS among sample adult Mexican workers. A total of 204 workers aged 20-56 were evaluated. Anthropometric index, blood pressure, fasting plasma glucose, and lipid profile were measured by spectrophotometric methods. Fasting insulin and leptin were measured by inmunoenzimatic methods. Furthermore, homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. The prevalence of MetS according to the ATP-III criteria was 33.8% and leptin concentrations were 2.5 times higher in women than men. Subjects with MetS had higher levels of leptin (26.7 ± 13.7) compared with those without MetS (20.1 ± 13.9; P <0.001). Leptin increased significantly while BMI increased as well (normal 14.0 ± 8.9, overweight 22.7 ± 11.7 and obese 31.4 ± 14.6) in addition to other variables such as WC, HDL-C, insulin levels, and HOMA index. Each component of MetS was stratified by sex and submitted by linear regression with a 95% of accuracy. The 50% and 53% of the BMI is explained by the concentration of leptin in men and women, respectively (P < 0.001). This study found that leptin was associated with the MetS, especially in obesity and insulin resistance, indicating a high risk for university workers to develop hypertension, DM2, and cardiovascular disease. © 2014 Wiley Periodicals, Inc.

  5. GH Receptor Deficiency in Ecuadorian Adults Is Associated With Obesity and Enhanced Insulin Sensitivity

    PubMed Central

    Rosenbloom, Arlan L.; Balasubramanian, Priya; Teran, Enrique; Guevara-Aguirre, Marco; Guevara, Carolina; Procel, Patricio; Alfaras, Irene; De Cabo, Rafael; Di Biase, Stefano; Narvaez, Luis; Saavedra, Jannette

    2015-01-01

    Context: Ecuadorian subjects with GH receptor deficiency (GHRD) have not developed diabetes, despite obesity. Objective: We sought to determine the metabolic associations for this phenomenon. Design: Four studies were carried out: 1) glucose, lipid, adipocytokine concentrations; 2) metabolomics evaluation; 3) metabolic responses to a high-calorie meal; and 4) oral glucose tolerance tests. Setting: Clinical Research Institute in Quito, Ecuador. Subjects: Adults homozygous for the E180 splice mutation of the GH receptor (GHRD) were matched for age, gender, and body mass index with unaffected control relatives (C) as follows: study 1, 27 GHRD and 35 C; study 2, 10 GHRD and 10 C; study 3, seven GHRD and 11 C; and study 4, seven GHRD and seven C. Results: Although GHRD subjects had greater mean percentage body fat than controls, their fasting insulin, 2-hour blood glucose, and triglyceride levels were lower. The indicator of insulin sensitivity, homeostasis model of assessment 2%S, was greater (P < .0001), and the indicator of insulin resistance, homeostasis model of assessment 2-IR, was lower (P = .0025). Metabolomic differences between GHRD and control subjects were consistent with their differing insulin sensitivity, including postprandial decreases of branched-chain amino acids that were more pronounced in controls. High molecular weight and total adiponectin concentrations were greater in GHRD (P = .0004 and P = .0128, respectively), and leptin levels were lower (P = .02). Although approximately 65% the weight of controls, GHRD subjects consumed an identical high-calorie meal; nonetheless, their mean glucose concentrations were lower, with mean insulin levels one-third those of controls. Results of the 2-hour oral glucose tolerance test were similar. Main Outcome Measures: Measures of insulin sensitivity, adipocytokines, and energy metabolites. Conclusions: Without GH counter-regulation, GHRD is associated with insulin efficiency and obesity. Lower leptin levels

  6. Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats.

    PubMed

    Zhao, M; Li, Y; Wang, J; Ebihara, K; Rong, X; Hosoda, K; Tomita, T; Nakao, K

    2011-12-01

    Hypertension often coexists with insulin resistance. However, most metabolic effects of the antihypertensive agents have been investigated in nomotensive animals, in which different conclusions may arise. We investigated the metabolic effects of the new angiotensin II type 1 receptor blocker azilsartan using the obese Koletsky rats superimposed on the background of the spontaneously hypertensive rats. Male Koletsky rats were treated with azilsartan (2 mg/kg/day) over 3 weeks. Blood pressure was measured by tail-cuff. Blood biochemical and hormonal parameters were determined by enzymatic or ELISA methods. Gene expression was assessed by RT-PCR. In Koletsky rats, azilsartan treatment lowered blood pressure, basal plasma insulin concentration and the homeostasis model assessment of insulin resistance index, and inhibited over-increase of plasma glucose and insulin concentrations during oral glucose tolerance test. These effects were accompanied by decreases in both food intake and body weight (BW) increase. Although two treatments showed the same effect on BW gain, insulin sensitivity was higher after azilsartan treatment than pair-feeding. Azilsartan neither affected plasma concentrations of triglyceride and free fatty acids, nor increased adipose mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ and its target genes such as adiponectin, aP2. In addition, azilsartan downregulated 11β-hydroxysteroid dehydrogenase type 1 expression. These results show the insulin-sensitizing effect of azilsartan in obese Koletsky rats. This effect is independent of decreases in food intake and BW increase or of the activation of adipose PPARγ. Our findings indicate the possible usefulness of azilsartan in the treatment of metabolic syndrome. © 2011 Blackwell Publishing Ltd.

  7. Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats.

    PubMed

    Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Teerapornpuntakit, Jarinthorn; Aeimlapa, Ratchaneevan; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2018-02-02

    Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  8. Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance

    PubMed Central

    Palanivel, R.; Fullerton, M. D.; Galic, S.; Honeyman, J.; Hewitt, K. A.; Jorgensen, S. B.; Steinberg, G. R.

    2017-01-01

    Aims/hypothesis Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known. Methods We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed. Results The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic–euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1). Conclusions/interpretation These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity. PMID:22872213

  9. Obesity: genes, glands or gluttony?

    PubMed

    Chisholm, D J; Samaras, K; Markovic, T; Carey, D; Lapsys, N; Campbell, L V

    1998-01-01

    Distribution as well as amount of fat has health implications; central abdominal fat seems to be the major contributor to insulin resistance and risk of diabetes, hypertension and cardiovascular disease. Physical activity and diet affect overall adiposity; moreover, exercise specifically reduces visceral fat. The sexes differ in fat distribution; in particular, pre-menopausal women, despite greater overall adiposity, have much less visceral fat than men. There is a strong genetic determination of overall obesity and central abdominal adiposity. Genes regulating obesity (e.g. Ob) could modulate appetite, satiety, metabolic rate or physical activity. Moderate obesity probably results from interaction between genetic predisposition and an environment of abundant calories and reduced physical activity. Single gene mutations are being identified in a few morbidly obese people; however, the common genetic predisposition for obesity may relate to more subtle variations in regulatory controls. Diet and exercise are effective for some, but the response is often disappointing. Definition of pathways controlling appetite, metabolic rate and lipid metabolism may generate improved pharmacological compounds. Education and availability of lower-energy foods may help, but more radical approaches may be needed, such as environmental restructuring to increase physical activity. The problem is great, but failure will mean intolerably increased health costs.

  10. Effects of fasting on insulin action and glucose kinetics in lean and obese men and women.

    PubMed

    Bergman, Bryan C; Cornier, Marc-Andre; Horton, Tracy J; Bessesen, Daniel H

    2007-10-01

    The development of insulin resistance in the obese individual could impair the ability to appropriately adjust metabolism to perturbations in energy balance. We investigated a 12- vs. 48-h fast on hepatic glucose production (R(a)), peripheral glucose uptake (R(d)), and skeletal muscle insulin signaling in lean and obese subjects. Healthy lean [n = 14; age = 28.0 +/- 1.4 yr; body mass index (BMI) = 22.8 +/- 0.42] and nondiabetic obese (n = 11; age = 34.6 +/- 2.3 yr; BMI = 36.1 +/- 1.5) subjects were studied following a 12- and 48-h fast during 2 h of rest and a 3-h 40 mUxm(-2)xmin(-1) hyperinsulinemic-euglycemic clamp (HEC). Basal glucose R(a) decreased significantly from the 12- to 48-h fast (lean 1.96 +/- 0.23 to 1.63 +/- 0.15; obese 1.23 +/- 0.07 to 1.07 +/- 0.07 mgxkg(-1)xmin(-1); P = 0.004) and was equally suppressed during the HEC after both fasts. The increase in glucose R(d) during the HEC after the 12-h fast was significantly decreased in lean and obese subjects after the 48-h fast (lean 9.03 +/- 1.17 to 4.16 +/- 0.34, obese 6.10 +/- 0.77 to 3.56 +/- 0.30 mgxkg FFM(-1)xmin(-1); P < 0.001). After the 12- but not the 48-h fast, insulin-stimulated AKT Ser(473) phosphorylation was greater in lean than obese subjects. We conclude that 1) 48 h of fasting produces a marked decline in peripheral insulin action, while suppression of hepatic glucose production is maintained in lean and obese men and women; and 2) the magnitude of this decline is greater in lean vs. obese subjects.

  11. Abdominal Subcutaneous Fat Thickness Measured by Ultrasonography Correlates with Hyperlipidemia and Steatohepatitis in Obese Children.

    PubMed

    Lee, Sung Hyun; Kim, Dongwan; Baek, Min Young; Tchah, Hann; Kim, Yeon Sun; Ryoo, Eell; Kim, Yun Mi

    2015-06-01

    The aim of this study is to evaluate the relationship between abdominal subcutaneous fat thickness measured by ultrasonography (US) and serum lipid profile and liver transaminases in obese children. One hundred and sixty-six children diagnosed with obesity from May 2001 to December 2013 were included in this study. Data on serum lipid profile and liver transaminases were collected from clinical records. Abdominal subcutaneous fat thickness and grade of hepatic steatosis were evaluated by US. Of the 166 children, 107 were diagnosed with hepatic steatosis by US, 46 with grade I, 56 with grade II, and five children with grade III. According to the grade of hepatic steasosis, the average values of midline abdominal subcutaneous fat thickness and right flank abdominal subcutaneous fat thickness measured 2.9±0.8 cm and 1.9±0.7 cm in the normal group, 3.3±0.8 cm and 2.0±0.7 cm in grade I, 3.8±0.8 cm and 2.3±0.8 cm in grade II, and 4.1±0.8 cm and 2.8±1.4 cm in grade III, respectively. Abdominal subcutaneous fat thickness correlated with grade of hepatic steatosis (p<0.01). In addition, abdominal subcutaneous fat thickness correlated with concentration of serum lipids and liver transaminases in the age group of 12-14 years (p<0.01). Abdominal subcutaneous fat thickness measured by US can be used as a reliable predictor of possible hyperlipidemia and steatohepatitis in children, especially during the adolescent stage.

  12. Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study.

    PubMed

    Suk, Seung-Han; Sacco, Ralph L; Boden-Albala, Bernadette; Cheun, Jian F; Pittman, John G; Elkind, Mitchell S; Paik, Myunghee C

    2003-07-01

    Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Our aim was to evaluate abdominal obesity as an independent risk factor for ischemic stroke in a multiethnic community. A population-based, incident case-control study was conducted July 1993 through June 1997 in northern Manhattan, New York, NY. Cases (n=576) of first ischemic stroke (66% >or=BORDER="0">65 years of age; 56% women; 17% whites; 26% blacks; 55% Hispanics) were enrolled and matched by age, sex, and race-ethnicity to stroke-free community controls (n=1142). All subjects were interviewed and examined and had measurements of waist-to-hip ratio (WHR). Odds ratios (ORs) of ischemic stroke were calculated with gender-specific quartiles (GQs) and gender-specific medians of WHR adjusted for stroke risk factors and body mass index (BMI). Compared with the first quartile, the third and fourth quartiles of WHR had an increased risk of stroke (GQ3: OR, 2.4; 95% CI, 1.5 to 3.9; GQ4: OR, 3.0; 95% CI, 1.8 to 4.8) adjusted for other risk factors and BMI. Those with WHR equal to or greater than the median had an overall OR of 3.0 (95% CI, 2.1 to 4.2) for ischemic stroke even after adjustment for other risk factors and BMI. Increased WHR was associated with a greater risk of stroke in men and women and in all race-ethnic groups. The effect of WHR was stronger among younger persons (test for heterogeneity, P<0.0002) (<65 years of age: OR, 4.4; 95%CI, 2.2 to 9.0; >or=65 years of age: OR, 2.2; 95% CI, 1.4 to 3.2). WHR was associated with an increased risk among those with and without large-artery atherosclerotic stroke. Abdominal obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. Prevention of obesity and weight reduction need greater emphasis in stroke prevention programs.

  13. Immunity as a link between obesity and insulin resistance

    USDA-ARS?s Scientific Manuscript database

    Type-2 diabetes mellitus (T2DM) is a major health problem in the United States and worldwide. Obesity is causally linked to the pathogenesis of insulin resistance, metabolic syndrome and T2DM. A chronic low-grade inflammation occurring in adipose tissue is at least in part responsible for the obesit...

  14. Contributions of dysglycemia, obesity and insulin resistance to impaired endothelium-dependent vasodilation in humans

    PubMed Central

    Han, KA; Patel, Y; Lteif, AA; Chisholm, R; Mather, KJ

    2011-01-01

    Background Individual effects of hyperglycemia and obesity to impair vascular health are recognized. However, the relative contributions of dysglycemia versus other obesity-related traits to vascular dysfunction have not been systematically evaluated. Methods We undertook a cross-sectional evaluation of factors contributing to vascular function in 271 consecutive subjects, categorized as non-obese normal glucose tolerant (n=115), non-obese dysglycemic (n=32), obese normal glucose tolerant (n=57), obese dysglycemic (n=38), or type 2 diabetic (n=29). Vascular function was measured invasively as leg blood flow responses to methacholine chloride, an endothelium-dependent vasodilator. Categorical and continuous analyses were used to assess the contributions of hyperglycemia to vascular dysfunction. Results Even among normoglycemic subjects, obese subjects had impaired vascular function compared to non-obese subjects (p=0.004). Vascular function was also impaired in non-obese dysglycemic subjects (p=0.04 versus non-obese normoglycemic subjects), to a level comparable to normoglycemic obese subjects. Within obese subject groups, gradations of dysglycemia including the presence of diabetes were not associated with further worsening of these vascular responses beyond the effect of obesity alone (p=NS comparing all obese groups, p<0.001 versus lean normoglycemic subjects). In univariate and multivariable modeling analyses we found that effects of glycemia were less powerful than effects of insulin resistance and obesity on vascular dysfunction. Conclusions Dysglycemia contributes to impaired vascular function in non-obese subjects, but obesity and insulin resistance are more important determinants of vascular function in obese and diabetic subjects. PMID:21309061

  15. Epidemiology of general obesity, abdominal obesity and related risk factors in urban adults from 33 communities of northeast china: the CHPSNE study

    PubMed Central

    2012-01-01

    Background Obesity increases the risk of many diseases. However, there has been little literature about the epidemiology of obesity classified by body mass index (BMI) or waist (abdominal obesity) among urban Chinese adults. This study is to fill the gap by assessing the prevalence of obesity and associated risk factors among urban Chinese adults. Methods A representative sample of 25,196 urban adults aged 18 to 74 years in Northeast China was selected and measurements of height, weight and waist circumference (WC) were taken from 2009–2010. Definitions of overweight and obesity by the World Health Organization (WHO) were used. Results The overall prevalence rates of general obesity and overweight classified by BMI were 15.0% (15.7% for men and 14.3% for women, p<0.01) and 19.2% (20.8% for men and 17.7% for women, p<0.01), respectively, and the overall prevalence rate of abdominal obesity was 37.6% (31.1% for men and women 43.9% for women, p<0.01). Multivariable logistic regression showed that the elderly and those who had a history of parental obesity, alcohol drinking, or former cigarette smoking were at high risk of obesity classified by BMI or WC, whereas those with a higher level of education, higher family income, or a healthy and balanced diet were at low risk of obesity. Analysis stratified by gender showed that men with a higher level education level, a white-collar job, a cadre job, or higher family income were the high risk group, and women with a higher level of education or higher family income were the low risk group. Conclusions Obesity and overweight have become epidemic in urban populations in China; associations of risk factors with obesity differ between men and women. PMID:23146089

  16. Association Between Insulin Resistance and Oxidative Stress Parameters in Obese Adolescents with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Pirgon, Özgür; Bilgin, Hüseyin; Çekmez, Ferhat; Kurku, Hüseyin; Dündar, Bumin Nuri

    2013-01-01

    Objective: Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in children. The aim of this study was to investigate the associations of oxidative stress with insulin resistance and metabolic risk factors in obese adolescents with NAFLD. Methods: Forty-six obese adolescents (23 girls and 23 boys, mean age: 12.8±2.2 years) and 29 control subjects (15 girls and 14 boys, mean age: 12.7±2.7 years) were enrolled in the study. The obese subjects were divided into two groups (NAFLD group and non-NAFLD group) based on the elevated alanine aminotransferase levels (>30 IU/L) and the presence or absence of liver steatosis detected by ultrasonography. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. Plasma total antioxidant status (TAS) and total oxidant status (TOS) level measurements (REL Assay Diagnostics) were done in all participants. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of OS. Results: Fasting insulin levels and HOMA-IR values in the NAFLD group were significantly higher than in the non-NAFLD and control groups. TAS measurements were decreased in both obese groups (NAFLD and non-NAFLD) in comparison with the control group. TOS and OSI measurements were higher in the NAFLD group than in the non-NAFLD and control groups. OSI was positively correlated with fasting insulin (r=0.67, p=0.01) and HOMA-IR (r=0.71, p=0.02) in the NAFLD obese group. Conclusions: In this cross-sectional study, elevated OS markers in obese adolescents with NAFLD were associated with insulin resistance. This data suggest that an antioxidant therapy might have a potential for treating NAFLD associated with insulin resistance. Conflict of interest:None declared. PMID:23367495

  17. Association between insulin resistance and oxidative stress parameters in obese adolescents with non-alcoholic fatty liver disease.

    PubMed

    Pirgon, Özgür; Bilgin, Hüseyin; Çekmez, Ferhat; Kurku, Hüseyin; Dündar, Bumin Nuri

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in children. The aim of this study was to investigate the associations of oxidative stress with insulin resistance and metabolic risk factors in obese adolescents with NAFLD. Forty-six obese adolescents (23 girls and 23 boys, mean age: 12.8 ± 2.2 years) and 29 control subjects (15 girls and 14 boys, mean age: 12.7 ± 2.7 years) were enrolled in the study. The obese subjects were divided into two groups (NAFLD group and non-NAFLD group) based on the elevated alanine aminotransferase levels (>30 IU/L) and the presence or absence of liver steatosis detected by ultrasonography. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. Plasma total antioxidant status (TAS) and total oxidant status (TOS) level measurements (REL Assay Diagnostics) were done in all participants. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of OS. Fasting insulin levels and HOMA-IR values in the NAFLD group were significantly higher than in the non-NAFLD and control groups. TAS measurements were decreased in both obese groups (NAFLD and non-NAFLD) in comparison with the control group. TOS and OSI measurements were higher in the NAFLD group than in the non-NAFLD and control groups. OSI was positively correlated with fasting insulin (r=0.67, p=0.01) and HOMA-IR (r=0.71, p=0.02) in the NAFLD obese group. In this cross-sectional study, elevated OS markers in obese adolescents with NAFLD were associated with insulin resistance. This data suggest that an antioxidant therapy might have a potential for treating NAFLD associated with insulin resistance.

  18. Insulin response to a spontaneously ingested standard meal during the development of obesity in GTG-injected mice.

    PubMed

    Blair, S C; Caterson, I D; Cooney, G J

    1996-04-01

    (1) To determine glucose and insulin levels in response to ingestion of a standard meal during the development of gold-thioglucose (GTG)-induced obesity. (2) To examine whether the pancreatic beta-cells of GTG-injected mice possess sufficient insulin secretory capacity to compensate for the increasing tissue insulin resistance that occurs with the development of this obesity. The insulin secretory response to a standard meal of chow was examined in chronically catheterised conscious mice 2, 5 and 10 weeks after induction of obesity by a single injection of GTG. At 2 weeks after administration of GTG both the basal insulinaemia and the incremental area under the curve (iAUC) of insulin release after a chow meal were increased compared with age-matched lean control mice (2 week control: 1004 +/- 316 min/microU/ml; 2 week GTG: 1968 +/- 300 min/microU/ml; P < 0.05). By 5 weeks, the GTG-injected mice were approximately 42% heavier than their lean controls and showed a marked glucose intolerance. This was accompanied by hyperinsulinaemia in both the basal state and also in response to ingestion of the chow meal as indicated by the increase in the iAUC of insulin (5 week control: 1113 +/- 331 min/microU/ml; 5 week GTG: 2682 +/- 295 min/microU/ml; P < 0.05). At 10 weeks after GTG administration body weight was further increased, as was the degree of glucose intolerance. Plasma insulin levels, in both the basal state and in response to the ingestion of chow, were also further elevated by 10 weeks following GTG injection (10 week control: 1234 +/- 311 min/microU/ml; 10 week GTG: 6640 +/- 1198 min/microU/ml; P < 0.05). It is apparent that the secretion of insulin in response to a standard chow meal increases progressively with the development of obesity. This finding, in conjunction with an earlier study showing that the insulin secretory response to intravenously administered glucose becomes impaired in the latter stages of the development of obesity in GTG-injected mice

  19. Roles of oxidative stress, adiponectin, and nuclear hormone receptors in obesity-associated insulin resistance and cardiovascular risk.

    PubMed

    Matsuda, Morihiro; Shimomura, Iichiro

    2014-08-01

    Obesity leads to the development of type 2 diabetes mellitus, which is a strong risk factor for cardiovascular disease. A better understanding of the molecular basis of obesity will lead to the establishment of effective prevention strategies for cardiovascular diseases. Adipocytes have been shown to generate a variety of endocrine factors termed adipokines/adipocytokines. Obesity-associated changes to these adipocytokines contribute to the development of cardiovascular diseases. Adiponectin, which is one of the most well-characterized adipocytokines, is produced exclusively by adipocytes and exerts insulin-sensitizing and anti-atherogenic effects. Obese subjects have lower levels of circulating adiponectin, and this is recognized as one of the factors involved in obesity-induced insulin resistance and atherosclerosis. Another pathophysiological feature of obesity may involve the low-grade chronic inflammation in adipose tissue. This inflammatory process increases oxidative stress in adipose tissue, which may affect remote organs, leading to the development of diabetes, hypertension, and atherosclerosis. Nuclear hormone receptors (NRs) regulate the transcription of the target genes in response to binding with their ligands, which include metabolic and nutritional substrates. Among the various NRs, peroxisome proliferator-activated receptor γ promotes the transcription of adiponectin and antioxidative enzymes, whereas mineralocorticoid receptor mediates the effects of aldosterone and glucocorticoid to induce oxidative stress in adipocytes. It is hypothesized that both play crucial roles in the pathophysiology of obesity-associated insulin resistance and cardiovascular diseases. Thus, reduced adiponectin and increased oxidative stress play pathological roles in obesity-associated insulin resistance to increase the cardiovascular disease risk, and various NRs may be involved in this pathogenesis.

  20. Association of acrylamide hemoglobin biomarkers with obesity, abdominal obesity and overweight in general US population: NHANES 2003-2006.

    PubMed

    Huang, Mengmeng; Zhuang, Pan; Jiao, Jingjing; Wang, Jun; Zhang, Yu

    2018-08-01

    Exposure to chemical contaminants is considered as one of risk factors to the current epidemic of obesity. Acrylamide (AA) is a ubiquitous chemical contaminant in environmental waste, mainstream cigarette smoke and carbohydrate-rich foods, and widely used in industrial manufacturers and cosmetics. Few studies have highlighted the association of daily exposure to AA with obesity-related outcomes. We analyzed data from 8364 participants who aged 20-85years and were recruited in National Health and Nutrition Examination Surveys (NHANES) 2003-2006. We established the model of PROC Survey Logistic regressions via using AA biomarkers in blood, hemoglobin adducts of acrylamide and glycidamide (HbAA and HbGA), as the measure of internal exposure to AA, and assessing obesity, abdominal obesity and overweight with body mass index (BMI) or waist circumference (WC). After the adjustment of sociodemographic variables, lifestyle behaviors, and health-related factors, the ratio of HbGA to HbAA (HbGA/HbAA) was significantly associated with obesity (p for trend<0.0001). The odd ratios (ORs) with 95% confidence intervals (CIs) of HbGA/HbAA across increasing quartiles were 1.740 (1.413-2.144), 2.604 (2.157-3.144), and 2.863 (2.425-3.380) compared with the lowest quartile. HbGA was positively associated with obesity [OR (95% CI): 1.226 (1.041-1.443), 1.283 (1.121-1.468), and 1.398 (1.165-1.679); p for trend=0.0004], while HbAA was inversely associated with obesity [OR (95% CI): 0.839 (0.718-0.980), 0.713 (0.600-0.848), and 0.671 (0.554-0.811); p for trend<0.0001]. Negative associations were found between the sum of HbAA and HbGA (HbAA+HbGA) and the body weight outcomes. Similar associations were also observed between the hemoglobin biomarkers of AA and abdominal obesity as well as overweight. Thus, the hemoglobin adducts of AA as long-term internal exposure biomarkers are strongly associated with obesity-related outcomes in a population of US adults. Copyright © 2018 Elsevier B

  1. Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness.

    PubMed

    Stuart, Charles A; Lee, Michelle L; South, Mark A; Howell, Mary E A; Cartwright, Brian M; Ramsey, Michael W; Stone, Michael H

    2017-03-01

    Stuart, CA, Lee, ML, South, MA, Howell, MEA, Cartwright, BM, Ramsey, MW, and Stone, MH. Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798-808, 2017-Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow-twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and glucose transporter type 4 (GLUT4) expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole-body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not

  2. The gut microbiota, obesity and insulin resistance.

    PubMed

    Shen, Jian; Obin, Martin S; Zhao, Liping

    2013-02-01

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate

  3. Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ding, Lili; Li, Jinmei

    Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gainmore » and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance. - Highlights: • Curcumin decreases biosynthesis of cholesterol and fatty acid in vitro. • Curcumin as a SREBP inhibitor ameliorates HFD-induced obesity. • Curcumin as a SREBP inhibitor improves insulin resistance.« less

  4. Molecular adaptations of adipose tissue to 6 weeks of morning fasting vs. daily breakfast consumption in lean and obese adults.

    PubMed

    Gonzalez, Javier T; Richardson, Judith D; Chowdhury, Enhad A; Koumanov, Francoise; Holman, Geoffrey D; Cooper, Scott; Thompson, Dylan; Tsintzas, Kostas; Betts, James A

    2018-02-15

    In lean individuals, 6 weeks of extended morning fasting increases the expression of genes involved in lipid turnover (ACADM) and insulin signalling (IRS2) in subcutaneous abdominal adipose tissue. In obese individuals, 6 weeks of extended morning fasting increases IRS2 expression in subcutaneous abdominal adipose tissue. The content and activation status of key proteins involved in insulin signalling and glucose transport (GLUT4, Akt1 and Akt2) were unaffected by extended morning fasting. Therefore, any observations of altered adipose tissue insulin sensitivity with extended morning fasting do not necessarily require changes in insulin signalling proximal to Akt. Insulin-stimulated adipose tissue glucose uptake rates are lower in obese versus lean individuals, but this difference is abolished when values are normalised to whole-body fat mass. This suggests a novel hypothesis which proposes that the reduced adipose glucose uptake in obesity is a physiological down-regulation to prevent excessive de novo lipogenesis. This study assessed molecular responses of human subcutaneous abdominal adipose tissue (SCAT) to 6 weeks of morning fasting. Forty-nine healthy lean (n = 29) and obese (n = 20) adults provided SCAT biopsies before and after 6 weeks of morning fasting (FAST; 0 kcal until 12.00 h) or daily breakfast consumption (BFAST; ≥700 kcal before 11.00 h). Biopsies were analysed for mRNA levels of selected genes, and GLUT4 and Akt protein content. Basal and insulin-stimulated Akt activation and tissue glucose uptake rates were also determined. In lean individuals, lipid turnover and insulin signalling genes (ACADM and IRS2) were up-regulated with FAST versus BFAST (ACADM: 1.14 (95% CI: 0.97-1.30) versus 0.80 (95% CI: 0.64-0.96), P = 0.007; IRS2: 1.75 (95% CI: 1.33-2.16) versus 1.09 (95% CI: 0.67-1.51), P = 0.03, respectively). In obese individuals, no differential (FAST versus BFAST) expression was observed in genes involved in lipid turnover (all

  5. Cardiovascular fitness, insulin resistance and metabolic syndrome in severely obese prepubertal Italian children.

    PubMed

    Brufani, Claudia; Grossi, Armando; Fintini, Danilo; Fiori, Rossana; Ubertini, Graziamaria; Colabianchi, Diego; Ciampalini, Paolo; Tozzi, Alberto; Barbetti, Fabrizio; Cappa, Marco

    2008-01-01

    To evaluate if insulin resistance (IR) and metabolic syndrome (MS) were associated with poor cardiovascular fitness in very obese prepubertal Italian subjects. Children referred to the Endocrinology and Diabetes Unit of Bambino Gesù Children's Hospital underwent an OGTT with glucose and insulin assays. QUICKI, ISI and HOMA-IR were calculated. Total and HDL cholesterol, triglycerides and percentage of body fat (DEXA) were determined. Cardiovascular fitness (maximal treadmill time) was evaluated using a treadmill protocol. The MS was defined as having 3 or more of following risk factors: obesity, impaired glucose tolerance, high blood pressure, low HDL-cholesterol, high triglycerides. Fifty-five very obese prepubertal Italian children were enrolled in the study. Unadjusted correlation revealed maximal treadmill time negatively related to fasting insulin (r = -0.53, p < 0.0001) and HOMA-IR (r = -0.57, p < 0.0001) and positively to QUICKI (r = 0.51, p < 0.0001) and ISI (r = 0.46, p = 0.0035). These relationships remained significant when in multivariate analysis age, gender, BMI SD and body composition were accounted for (all p < 0.01). The presence of the MS was independently associated with maximal treadmill time. Poorcardiovascular fitness, IR and MS were independently related, suggesting that the relationship between fitness and insulin action develops early in life. Copyright 2008 S. Karger AG, Basel.

  6. Predictive equations for central obesity via anthropometrics, stereovision imaging, and MRI in adults

    PubMed Central

    Lee, Jane J; Freeland-Graves, Jeanne H; Pepper, M Reese; Yao, Ming; Xu, Bugao

    2013-01-01

    Objective Abdominal visceral adiposity is related to risks for insulin resistance and metabolic perturbations. Magnetic resonance imaging (MRI) and computed tomography are advanced instruments that quantify abdominal adiposity; yet field use is constrained by their bulkiness and costliness. The purpose of this study is to develop prediction equations for total abdominal, subcutaneous, and visceral adiposity via anthropometrics, stereovision body imaging (SBI), and MRI. Design and Methods Participants (67 men and 55 women) were measured for anthropometrics, and abdominal adiposity volumes evaluated by MRI umbilicus scans. Body circumferences and central obesity were obtained via SBI. Prediction models were developed via multiple linear regression analysis, utilizing body measurements and demographics as independent predictors, and abdominal adiposity as a dependent variable. Cross-validation was performed by the data-splitting method. Results The final total abdominal adiposity prediction equation was –470.28+7.10waist circumference–91.01gender+5.74sagittal diameter (R²=89.9%); subcutaneous adiposity was –172.37+8.57waist circumference–62.65gender–450.16stereovision waist-to-hip ratio (R²=90.4%); and visceral adiposity was –96.76+11.48central obesity depth–5.09 central obesity width+204.74stereovision waist-to-hip ratio–18.59gender (R²=71.7%). R² significantly improved for predicting visceral fat when SBI variables were included, but not for total abdominal or subcutaneous adiposity. Conclusions SBI is effective for predicting visceral adiposity and the prediction equations derived from SBI measurements can assess obesity. PMID:23613161

  7. Comparative effects of several simple carbohydrates on erythrocyte insulin receptors in obese subjects.

    PubMed

    Rizkalla, S W; Baigts, F; Fumeron, F; Rabillon, B; Bayn, P; Ktorza, A; Spielmann, D; Apfelbaum, M

    1986-09-01

    The effects of simple carbohydrates on erythrocyte insulin receptors, plasma insulin and plasma glucose were studied during four hypocaloric, hyperproteic, diets. One diet contained no carbohydrate; the other three contained 36 g of either glucose, galactose or fructose. These diets were given for a 14-day period to groups of moderately obese subjects. The hypocaloric carbohydrate-free diet produced a decrease in plasma insulin and glucose concentrations concomitant with an increase in the number of insulin receptors. A similar increase in insulin receptor number was found when the diet was supplemented with glucose or galactose, but not with fructose. The presence of fructose in the diet prevented any increase in insulin receptor number.

  8. Neuropeptide Y genotype, central obesity, and abdominal fat distribution: the POUNDS LOST trial1,2

    PubMed Central

    Lin, Xiaochen; Qi, Qibin; Zheng, Yan; Huang, Tao; Lathrop, Mark; Zelenika, Diana; Bray, George A; Sacks, Frank M; Liang, Liming; Qi, Lu

    2015-01-01

    Background: Neuropeptide Y is a key peptide affecting adiposity and has been related to obesity risk. However, little is known about the role of NPY variations in diet-induced change in adiposity. Objective: The objective was to examine the effects of NPY variant rs16147 on central obesity and abdominal fat distribution in response to dietary interventions. Design: We genotyped a functional NPY variant rs16147 among 723 participants in the Preventing Overweight Using Novel Dietary Strategies trial. Changes in waist circumference (WC), total abdominal adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue (SAT) from baseline to 6 and 24 mo were evaluated with respect to the rs16147 genotypes. Genotype–dietary fat interaction was also examined. Results: The rs16147 C allele was associated with a greater reduction in WC at 6 mo (P < 0.001). In addition, the genotypes showed a statistically significant interaction with dietary fat in relation to WC and SAT (P-interaction = 0.01 and 0.04): the association was stronger in individuals with high-fat intake than in those with low-fat intake. At 24 mo, the association remained statistically significant for WC in the high-fat diet group (P = 0.02), although the gene–dietary fat interaction became nonsignificant (P = 0.30). In addition, we found statistically significant genotype–dietary fat interaction on the change in total abdominal adipose tissue, visceral adipose tissue, and SAT at 24 mo (P = 0.01, 0.05, and 0.04): the rs16147 T allele appeared to associate with more adverse change in the abdominal fat deposition in the high-fat diet group than in the low-fat diet group. Conclusion: Our data indicate that the NPY rs16147 genotypes affect the change in abdominal adiposity in response to dietary interventions, and the effects of the rs16147 single-nucleotide polymorphism on central obesity and abdominal fat distribution were modified by dietary fat. This trial was registered at clinicaltrials.gov as

  9. [PSYCHOEDUCATIONAL PROGRAM AS A WAY OF CORRECTING MOTIVATIONAL COMPONENTS IN PATIENTS WITH PARANOID SCHIZOPHRENIA WITH ABDOMINAL OBESITY].

    PubMed

    Sinayko, V; Korovina, L

    2016-01-01

    The aim of the study was to investigate the influence of motivational and targeted psychoeducational programs designed for patients with paranoid schizophrenia with abdominal obesity. We observed 34 women aged 18-42 with continuous-flow type paranoid schizophrenia. All patients had a concomitant abdominal obesity, which developed secondarily after long-term administration of second generation antipsychotic medications (at least 1 year). Based on clinical-psychopathological and psychometric methods of assessment and on the analysis of Treatment Satisfaction Questionnaire we have developed modules for psychoeducational programs. Based on the results of the treatment we conclude that the application of psychoeducational programs is an effective component of complex treatment of patients with paranoid schizophrenia. Abdominal obesity should be regarded as an important and the main side effect of long-term therapy with atypical antipsychotic medications. It has a marked negative effect on subjective assessment of patients and decreases the level of their mental and social adaptation. This factor should be the basis for the formation of re-socialization and compliance-oriented actions.

  10. The relationship between regional abdominal fat distribution and both insulin resistance and subclinical chronic inflammation in non-diabetic adults

    PubMed Central

    2014-01-01

    Objective Obesity is associated with a high risk of insulin resistance (IR) and its metabolic complications. It is still debated that distributions of adipose tissue relate to an excess risk of IR and chronic inflammation in different race. This study was designed to examine the relation between insulin sensitivity, chronic inflammation and central fat distribution in non-diabetic volunteers in Taiwanese. Methods There were 328 volunteers without family history of diabetes mellitus and with normal oral glucose tolerance test enrolled. Total body fat and abdominal fat were measured. Abdominal fat was categorized into intraperitoneal (IP), retroperitoneal (RP) and subcutaneous (SC) fat. The IR index was estimated by homeostatic model assessment. Five inflammatory markers: adiponectin, leptin, tumor necrosing factor-α (TNF-α), resistin and high sensitive CRP (hs-CRP) were measured. Results IR was related to IP fat (r = 0.23, p < 0.001), but not RP fat, SC fat or total body fat. After correcting for age and sex, IP fat was the only significant predictor of IR (r2 = 58%, p = 0.001). Leptin showed the strongest relationship with all fat compartments (IP fat: r = 0.44, p = 0.001; RP fat: r = 0.36, p = 0.005, SC fat: r = 0.54, p < 0.001; total body fat: r = 0.61, p < 0.001). The hs-CRP and adiponectin were closely related both to IP (r = 0.29, p = 0.004; r = -0.20, p = 0.046, respectively) and total body fat (r = 0.29, p = 0.004; r = -0.29, p = 0.005, respectively), but not RP, or SC fat. TNF-α and resistin were not correlated to any fat compartment. After correcting for age and sex, leptin variance was mostly explained by SC fat (41.3%), followed by IP fat (33.6%) and RP fat (25.3%). The hs-CRP and adiponectin variance were mostly explained by IP fat (40% and 49% respectively). Conclusions IP fat is better predictors of IR and subclinical chronic inflammation in Taiwanese adults. A

  11. Cytokines and their association with insulin resistance in obese pregnant women with different levels of physical activity.

    PubMed

    Nayak, Minakshi; Eekhoff, Marelise E W; Peinhaupt, Miriam; Heinemann, Akos; Desoye, Gernot; van Poppel, Mireille N M

    2016-01-01

    Cytokines contribute to insulin resistance in pregnancy, but the role of distinct cytokines is not fully understood. To study whether cytokines produced by tissues other than skeletal muscle are associated with glucose and insulin metabolism activity in overweight and obese women and to study whether these associations can be modified by physical activity. A longitudinal study with 44 overweight and obese pregnant women was conducted. Changes in cytokines levels (IFN-γ, IP-10, IL1-α, MIP1-α, adiponectin and leptin) and ICAM1 from early (15wk) to late (32wk) pregnancy were determined. Physical activity was measured objectively with accelerometers. In linear regression models, the associations between (changes in) cytokine levels and fasting glucose, fasting insulin and HOMA-IR were studied. Both IFN-γ and IP-10 levels increased from early to late pregnancy, and adiponectin levels decreased. IFN-γ and IP-10 were positively associated with fasting glucose, whereas IL-1α, ICAM1 and adiponectin were inversely associated with insulin and insulin resistance. The association of IL-1α with insulin and insulin resistance was only found in women with low levels of physical activity. IFN-γ, IP-10, IL1-α, ICAM1, and adiponectin may play a role in glucose and insulin metabolism in pregnancy. The relationship of IL-1α with insulin and insulin resistance might be moderated by levels of physical activity. Further studies are required to confirm the role of these cytokines in glucose and insulin metabolism in obese pregnant women. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Convergence in insulin resistance between very severely obese and lean women at the end of pregnancy.

    PubMed

    Forbes, Shareen; Barr, Sarah M; Reynolds, Rebecca M; Semple, Scott; Gray, Calum; Andrew, Ruth; Denison, Fiona C; Walker, Brian R; Norman, Jane E

    2015-11-01

    Disrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity. Our aim was to study metabolism in such pregnancies. We recruited a longitudinal cohort of very severely obese (n = 190) and lean (n = 118) glucose-tolerant women for anthropometric and metabolic measurements at early, mid and late gestation and postpartum. In case-control studies of very severely obese and lean women we measured glucose and glycerol turnover during low- and high-dose hyperinsulinaemic-euglycaemic clamps (HEC) at early and late pregnancy and in non-pregnant women (each n = 6-9) and body fat distribution by MRI in late pregnancy (n = 10/group). Although greater glucose, insulin, NEFA and insulin resistance (HOMA-IR), and greater weight and % fat mass (FM) was observed in very severely obese vs lean participants, the degree of worsening was attenuated in the very severely obese individuals with advancing gestation, with no difference in triacylglycerol (TG) concentrations between very severely obese and lean women at term. Enhanced glycerol production was observed in early pregnancy only in very severely obese individuals, with similar intrahepatic FM in very severely obese vs lean women by late gestation. Offspring from obese mothers were heavier (p = 0.04). Pregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women. Increased glycerol production is confined to obese women in early pregnancy and obese and lean individuals have similar intrahepatic FM by term. When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy.

  13. [Effect of oral administration of ascorbic acid on insulin sensitivity and lipid profile in obese individuals].

    PubMed

    Martínez-Abundis, E; Pascoe-González, S; González-Ortiz, M; Mora-Martínez, J M; Cabrera-Pivaral, C E

    2001-01-01

    The aim of this study was to identify the effect of an oral ascorbic acid (AA) supplement on lipid profile and insulin sensitivity in obese people. A randomized double-blind clinical trial placebo controlled was performed in 16 obese male volunteers [body mass index (BMI) 30-40 kg/m2]. Eight received orally 1 g of AA daily for four weeks and the other eight volunteers received placebo by the same scheme and period of time. Before and after the pharmacological intervention were measured total cholesterol, high-density-lipoprotein (HDL) cholesterol, triglycerides, glucose, creatinine and uric acid. Low-density-lipoprotein (LDL) cholesterol and very-low-density-lipoprotein (VLDL) triglycerides were calculated using formulas. In order to assess insulin sensitivity before and after the intervention, the steady-state glucose (SSG) was calculated from the insulin suppression test modified with octreotide. There were not significant differences in clinical characteristics between both groups. Basal metabolic profile and SSG were similar between both groups. There were not significant differences in both groups between before and after the intervention in metabolic profile and insulin sensitivity. AA did not modify the lipid profile nor insulin sensitivity in the group of obese people studied.

  14. The Gradual Shift of Overweight, Obesity, and Abdominal Obesity Towards the Poor in a Multi-ethnic Developing Country: Findings From the Malaysian National Health and Morbidity Surveys.

    PubMed

    Mariapun, Jeevitha; Ng, Chiu-Wan; Hairi, Noran N

    2018-06-05

    Economic development is known to shift the distribution of obesity from the socioeconomically more advantaged to the less advantaged. We assessed the socioeconomic trends in overweight, obesity, and abdominal obesity across a period of significant economic growth. We used the Malaysian National Health and Morbidity Survey data sets for the years 1996, 2006, and 2011 to analyze the trends among adults aged 30 years and above. The World Health Organization's Asian body mass index cut-off points of ≥23.0 kg/m 2 and ≥27.5 kg/m 2 were used to define overweight and obesity, respectively. Abdominal obesity was defined as having a waist circumference of ≥90 cm for men and ≥80 cm for women. Household per-capita income was used as a measure of socioeconomic position. As a summary measure of inequality, we computed the concentration index. Women in Peninsular Malaysia demonstrated patterns that were similar to that of developed countries in which the distributions for overweight, obesity, and abdominal obesity became concentrated among the poor. For women in East Malaysia, distributions became neither concentrated among the rich nor poor, while distributions for men were still concentrated among the rich. Chinese women, particularly from the richest quintile, had the lowest rates and lowest increase in overweight and obesity. All distributions of Chinese women were concentrated among the poor. The distributions of Malay men were still concentrated among the rich, while distributions for Chinese and Indian men and Malay and Indian women were neither concentrated among the rich nor poor. As the country continues to progress, increasing risks of overweight and obesity among the socioeconomically less advantaged is expected.

  15. Intake and Dietary Food Sources of Fibre in Spain: Differences with Regard to the Prevalence of Excess Body Weight and Abdominal Obesity in Adults of the ANIBES Study

    PubMed Central

    González-Rodríguez, Liliana G.; Perea Sánchez, José Miguel; Aranceta-Bartrina, Javier; Gil, Ángel; González-Gross, Marcela; Serra-Majem, Lluis; Varela-Moreiras, Gregorio; Ortega, Rosa M.

    2017-01-01

    The aim was to study the intake and food sources of fibre in a representative sample of Spanish adults and to analyse its association with excess body weight and abdominal obesity. A sample of 1655 adults (18–64 years) from the ANIBES (“Anthropometric data, macronutrients and micronutrients intake, practice of physical activity, socioeconomic data and lifestyles”) cross-sectional study was analysed. Fibre intake and dietary food sources were determined by using a three-day dietary record. Misreporters were identified using the protocol of the European Food Safety Authority. Mean (standard deviation) fibre intake was 12.59 (5.66) g/day in the whole sample and 15.88 (6.29) g/day in the plausible reporters. Mean fibre intake, both in the whole sample and the plausible reporters, was below the adequate intake established by European Food Safety Authority (EFSA) and the Institute of Medicine of the United States (IOM). Main fibre dietary food sources were grains, followed by vegetables, fruits, and pulses. In the whole sample, considering sex, and after adjusting for age and physical activity, mean (standard error) fibre intake (adjusted by energy intake) was higher in subjects who had normal weight (NW) 13.40 (0.184) g/day, without abdominal obesity 13.56 (0.192) g/day or without excess body weight and/or abdominal obesity 13.56 (0.207) g/day compared to those who were overweight (OW) 12.31 (0.195) g/day, p < 0.001 or obese (OB) 11.83 (0.266) g/day, p < 0.001, with abdominal obesity 12.09 (0.157) g/day, p < 0.001 or with excess body weight and/or abdominal obesity 12.22 (0.148) g/day, p < 0.001. There were no significant differences in relation with the fibre intake according to the body mass index (BMI), presence or absence of abdominal obesity or excess body weight and/or abdominal obesity in the plausible reporters. Fibre from afternoon snacks was higher in subjects with NW (6.92%) and without abdominal obesity (6.97%) or without excess body weight and

  16. Intake and Dietary Food Sources of Fibre in Spain: Differences with Regard to the Prevalence of Excess Body Weight and Abdominal Obesity in Adults of the ANIBES Study.

    PubMed

    González-Rodríguez, Liliana G; Perea Sánchez, José Miguel; Aranceta-Bartrina, Javier; Gil, Ángel; González-Gross, Marcela; Serra-Majem, Lluis; Varela-Moreiras, Gregorio; Ortega, Rosa M

    2017-03-25

    The aim was to study the intake and food sources of fibre in a representative sample of Spanish adults and to analyse its association with excess body weight and abdominal obesity. A sample of 1655 adults (18-64 years) from the ANIBES ("Anthropometric data, macronutrients and micronutrients intake, practice of physical activity, socioeconomic data and lifestyles") cross-sectional study was analysed. Fibre intake and dietary food sources were determined by using a three-day dietary record. Misreporters were identified using the protocol of the European Food Safety Authority. Mean (standard deviation) fibre intake was 12.59 (5.66) g/day in the whole sample and 15.88 (6.29) g/day in the plausible reporters. Mean fibre intake, both in the whole sample and the plausible reporters, was below the adequate intake established by European Food Safety Authority (EFSA) and the Institute of Medicine of the United States (IOM). Main fibre dietary food sources were grains, followed by vegetables, fruits, and pulses. In the whole sample, considering sex, and after adjusting for age and physical activity, mean (standard error) fibre intake (adjusted by energy intake) was higher in subjects who had normal weight (NW) 13.40 (0.184) g/day, without abdominal obesity 13.56 (0.192) g/day or without excess body weight and/or abdominal obesity 13.56 (0.207) g/day compared to those who were overweight (OW) 12.31 (0.195) g/day, p < 0.001 or obese (OB) 11.83 (0.266) g/day, p < 0.001, with abdominal obesity 12.09 (0.157) g/day, p < 0.001 or with excess body weight and/or abdominal obesity 12.22 (0.148) g/day, p < 0.001. There were no significant differences in relation with the fibre intake according to the body mass index (BMI), presence or absence of abdominal obesity or excess body weight and/or abdominal obesity in the plausible reporters. Fibre from afternoon snacks was higher in subjects with NW (6.92%) and without abdominal obesity (6.97%) or without excess body weight and/or abdominal

  17. The PPARα/γ dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats

    PubMed Central

    Li, Ping-Ping; Shan, Song; Chen, Yue-Teng; Ning, Zhi-Qiang; Sun, Su-Juan; Liu, Quan; Lu, Xian-Ping; Xie, Ming-Zhi; Shen, Zhu-Fang

    2006-01-01

    The aim of this study was to investigate the capacity of chiglitazar to improve insulin resistance and dyslipidemia in monosodium L-glutamate (MSG) obese rats and to determine whether its lipid-lowering effect is mediated through its activation of PPARα. Chiglitazar is a PPARα/γ dual agonist. The compound improved impaired insulin and glucose tolerance; decreased plasma insulin level and increased the insulin sensitivity index and decreased HOMA index. Euglycemic hyperinsulinemic clamp studies showed chiglitazar increased the glucose infusion rate in MSG obese rats. Chiglitazar inhibited alanine gluconeogenesis, lowered the hepatic glycogen level in MSG obese rats. Like rosiglitazone, chiglitazar promoted the differentiation of adipocytes and decreased the maximal diameter of adipocytes. In addition, chiglitazar decreased the fibrosis and lipid accumulation in the islets and increased the size of islets. Chiglitazar reduced plasma triglyceride, total cholesterol (TCHO), nonesterified fatty acids (NEFA) and low density lipoprotein-cholesterol levels; lowered hepatic triglyceride and TCHO contents; decreased muscular NEFA level. Unlike rosiglitazone, chiglitazar showed significant increase of mRNA expression of PPARα, CPT1, BIFEZ, ACO and CYP4A10 in the liver of MSG obese rats. These data suggest that PPARα/γ coagonist, such as chiglitazar, affect lipid homeostasis with different mechanisms from rosiglitazone, chiglitazar may have better effects on lipid homeostasis in diabetic patients than selective PPARγ agonists. PMID:16751799

  18. Accumulation of ceramide in slow-twitch muscle contributes to the development of insulin resistance in the obese JCR:LA-cp rat.

    PubMed

    Fillmore, Natasha; Keung, Wendy; Kelly, Sandra E; Proctor, Spencer D; Lopaschuk, Gary D; Ussher, John R

    2015-06-01

    What is the central question of this study? The aim was to determine whether the accumulation of ceramide contributes to skeletal muscle insulin resistance in the JCR obese rat. What is the main finding and its importance? Our main new finding is that ceramides accumulate only in slow-twitch skeletal muscle in the JCR obese rat and that reducing ceramide content in this muscle type by inhibition of serine palmitoyl transferase-1 halts the progression of insulin resistance in this rat model predisposed to early development of type 2 diabetes. Our findings highlight the importance of assessing insulin signalling/sensitivity and lipid intermediate accumulation in different muscle fibre types. It has been postulated that insulin resistance results from the accumulation of cytosolic lipid metabolites (i.e. diacylglycerol/ceramide) that impede insulin signalling and impair glucose homeostasis. De novo ceramide synthesis is catalysed by serine palmitoyl transferase-1. Our aim was to determine whether de novo ceramide synthesis plays a role during development of insulin resistance in the JCR:LA-cp obese rat. Ten-week-old JCR:LA-cp obese rats were supplemented with either vehicle or the serine palmitoyl transferase-1 inhibitor l-cycloserine (360 mg l(-1) ) in their drinking water for a 2 week period, and glycaemia was assessed by meal tolerance testing. Treatment of JCR:LA-cp obese rats with l-cycloserine improved their plasma glucose and insulin levels during a meal tolerance test. Examination of muscle lipid metabolites and protein phosphorylation patterns revealed differential signatures in slow-twitch (soleus) versus fast-twitch muscle (gastrocnemius), in that ceramide levels were increased in soleus but not gastrocnemius muscles of JCR:LA-cp obese rats. Likewise, improved glycaemia in l-cycloserine-treated JCR:LA-cp obese rats was associated with enhanced Akt and pyruvate dehydrogenase signalling in soleus but not gastrocnemius muscles, probably as a result of l

  19. Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats

    NASA Technical Reports Server (NTRS)

    Brooks-Asplund, Esther M.; Shoukas, Artin A.; Kim, Soon-Yul; Burke, Sean A.; Berkowitz, Dan E.

    2002-01-01

    We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.

  20. Unhealthy Phenotype as Indicated by Salivary Biomarkers: Glucose, Insulin, VEGF-A, and IL-12p70 in Obese Kuwaiti Adolescents

    PubMed Central

    Hartman, Mor-Li; Goodson, J. Max; Shi, Ping; Vargas, Jorel; Yaskell, Tina; Stephens, Danielle; Cugini, Maryann; Hasturk, Hatice; Barake, Roula; Alsmadi, Osama; Al-Mutawa, Sabiha; Ariga, Jitendra; Soparkar, Pramod; Behbehani, Jawad; Behbehani, Kazem; Welty, Francine

    2016-01-01

    Objective. Here, we investigated the relationships between obesity and the salivary concentrations of insulin, glucose, and 20 metabolic biomarkers in Kuwaiti adolescents. Previously, we have shown that certain salivary metabolic markers can act as surrogates for blood concentrations. Methods. Salivary samples of whole saliva were collected from 8,317 adolescents. Salivary glucose concentration was measured by a high-sensitivity glucose oxidase method implemented on a robotic chemical analyzer. The concentration of salivary insulin and 20 other metabolic biomarkers was assayed in 744 randomly selected saliva samples by multiplexed bead-based immunoassay. Results. Obesity was seen in 26.5% of the adolescents. Salivary insulin predicting hyperinsulinemia occurred in 4.3% of normal-weight adolescents, 8.3% of overweight adolescents, and 25.7% of obese adolescents (p < 0.0001). Salivary glucose predicting hyperglycemia was found in only 3% of obese children and was not predictive (p = 0.89). Elevated salivary glucose and insulin occurring together was associated with elevated vascular endothelial growth factor and reduced salivary interleukin-12. Conclusion. Considering the surrogate nature of salivary insulin and glucose, this study suggests that elevated insulin may be a dominant sign of metabolic disease in adolescent populations. It also appears that a proangiogenic environment may accompany elevated glucose in obese adolescents. PMID:27069678

  1. Cellular and Molecular Players in Adipose Tissue Inflammation in the Development of Obesity-induced Insulin Resistance

    PubMed Central

    Lee, Byung-Cheol; Lee, Jongsoon

    2013-01-01

    There is increasing evidence showing that inflammation is an important pathogenic mediator of the development of obesity-induced insulin resistance. It is now generally accepted that tissue-resident immune cells play a major role in the regulation of this obesity-induced inflammation. The roles that adipose tissue (AT)-resident immune cells play have been particularly extensively studied. AT contains most types of immune cells and obesity increases their numbers and activation levels, particularly in AT macrophages (ATMs). Other pro-inflammatory cells found in AT include neutrophils, Th1 CD4 T cells, CD8 T cells, B cells, DCs, and mast cells. However, AT also contains anti-inflammatory cells that counter the pro-inflammatory immune cells that are responsible for the obesity-induced inflammation in this tissue. These anti-inflammatory cells include regulatory CD4 T cells (Tregs), Th2 CD4 T cells, and eosinophils. Hence, AT inflammation is shaped by the regulation of pro- and anti-inflammatory immune cell homeostasis, and obesity skews this balance towards a more pro-inflammatory status. Recent genetic studies revealed several molecules that participate in the development of obesity-induced inflammation and insulin resistance. In this review, the cellular and molecular players that participate in the regulation of obesity-induced inflammation and insulin resistance are discussed, with particular attention being placed on the roles of the cellular players in these pathogeneses. PMID:23707515

  2. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes.

    PubMed

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J; Blaszczak, Alecia; Kashyap, Sangeeta R; Kirwan, John P

    2013-11-15

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P < 0.05). Exercise reduced glucose iAUCOGTT in IGT only (P < 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity (P < 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P < 0.05). Adults with IFG + IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

  3. Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods.

    PubMed

    Kurtoğlu, Selim; Hatipoğlu, Nihal; Mazıcıoğlu, Mümtaz; Kendirici, Mustafa; Keskin, Mehmet; Kondolot, Meda

    2010-01-01

    Childhood obesity is associated with an increased risk for insulin resistance. The underlying mechanism for the physiological increase in insulin levels in puberty is not clearly understood. The aim of the present study was to determine the cut-off values for homeostasis model assessment for insulin resistance (HOMA-IR) in obese children and adolescents according to gender and pubertal status. Two hundred and eight obese children and adolescents (141 girls, 127 boys) aged between 5 and 18 years were included in the study. The children were divided into prepubertal and pubertal groups. A standard oral glucose tolerance test (OGTT) was carried out in all children. A total insulin level exceeding 300 μU/mL in the blood samples, collected during the test period, was taken as the insulin resistance criterion. Cut-off values for HOMA-IR were calculated by receiver operating characteristic (ROC) analysis. In the prepubertal period, the rate of insulin resistance was found to be 37% in boys and 27.8% in girls,while in the pubertal period, this rate was 61.7% in boys and 66.7% in girls. HOMA-IR cut-off values for insulin resistance in the prepubertal period were calculated to be 2.67 (sensitivity 88.2%, specificity 65.5%) in boys and 2.22 (sensitivity 100%, specificity 42.3%) in girls, and in the pubertal period, they were 5.22 (sensitivity 56%, specificity 93.3%) in boys and 3.82 (sensitivity 77.1%, specificity 71.4%) in girls. Since gender, obesity and pubertal status are factors affecting insulin resistance, cut-off values which depend on gender and pubertal status, should be used in evaluation of insulin resistance.

  4. Changes in subcutaneous fat cell volume and insulin sensitivity after weight loss.

    PubMed

    Andersson, Daniel P; Eriksson Hogling, Daniel; Thorell, Anders; Toft, Eva; Qvisth, Veronica; Näslund, Erik; Thörne, Anders; Wirén, Mikael; Löfgren, Patrik; Hoffstedt, Johan; Dahlman, Ingrid; Mejhert, Niklas; Rydén, Mikael; Arner, Erik; Arner, Peter

    2014-07-01

    Large subcutaneous fat cells associate with insulin resistance and high risk of developing type 2 diabetes. We investigated if changes in fat cell volume and fat mass correlate with improvements in the metabolic risk profile after bariatric surgery in obese patients. Fat cell volume and number were measured in abdominal subcutaneous adipose tissue in 62 obese women before and 2 years after Roux-en-Y gastric bypass (RYGB). Regional body fat mass by dual-energy X-ray absorptiometry; insulin sensitivity by hyperinsulinemic-euglycemic clamp; and plasma glucose, insulin, and lipid profile were assessed. RYGB decreased body weight by 33%, which was accompanied by decreased adipocyte volume but not number. Fat mass in the measured regions decreased and all metabolic parameters were improved after RYGB (P < 0.0001). Whereas reduced subcutaneous fat cell size correlated strongly with improved insulin sensitivity (P = 0.0057), regional changes in fat mass did not, except for a weak correlation between changes in visceral fat mass and insulin sensitivity and triglycerides. The curve-linear relationship between fat cell size and fat mass was altered after weight loss (P = 0.03). After bariatric surgery in obese women, a reduction in subcutaneous fat cell volume associates more strongly with improvement of insulin sensitivity than fat mass reduction per se. An altered relationship between adipocyte size and fat mass may be important for improving insulin sensitivity after weight loss. Fat cell size reduction could constitute a target to improve insulin sensitivity. © 2014 by the American Diabetes Association.

  5. Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity.

    PubMed

    Broussard, Josiane L; Nelson, Michael D; Kolka, Cathryn M; Bediako, Isaac Asare; Paszkiewicz, Rebecca L; Smith, Laura; Szczepaniak, Edward W; Stefanovski, Darko; Szczepaniak, Lidia S; Bergman, Richard N

    2016-01-01

    The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n = 26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n = 12), a salmon oil diet (rich in polyunsaturated fat; n = 8) or a control diet (n = 6). High-fat feeding with lard increased body weight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased body weight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health.

  6. Herbal Formula HT048 Attenuates Diet-Induced Obesity by Improving Hepatic Lipid Metabolism and Insulin Resistance in Obese Rats.

    PubMed

    Lee, Yoon Hee; Jin, Bora; Lee, Sung Hyun; Song, MiKyung; Bae, HyeonHui; Min, Byung Jae; Park, Juyeon; Lee, Donghun; Kim, Hocheol

    2016-10-25

    It is well established that obesity causes a variety of chronic diseases such as cardiovascular diseases and diabetes. Despite the diligent scientific efforts to find effective ways to lower the level of obesity, the size of obese population grows continuously around the world. Here we present the results that show feeding diet containing HT048, a mixture of the extracts of Crataegus pinnatifida leaves and Citrus unshiu peel, two of the well-known traditional herbal medicines in Eastern Asia, decreases obesity in rats. We fed rats with five different diets for 10 weeks: chow diet (STD), high-fat diet (HFD), high-fat diet with 0.04% orlistat, a drug to treat obesity (HFD + Orlistat), high-fat diet with 0.2% HT048 ( w / w ; HFD + 0.2% HT048), and high-fat diet with 0.6% HT048 ( w / w ; HFD + 0.6% HT048). It was found that both body and total white adipose tissue weight of HT048 groups significantly decreased compared to those of the HFD group. Moreover, HT048 decreased serum insulin levels in HFD-fed obese rats. At the molecular level, HT048 supplementation downregulated genes involved in lipogenesis, gluconeogenesis, and adipogenesis, while the expression level of β-oxidation genes was increased. Supplementation-drug interactions are not likely as HFD and HT048-containing diet did not significantly induce genes encoding CYPs. Collectively, this study suggests that HT048 taken as dietary supplement helps to decrease obesity and insulin resistance in HFD-fed obese rats.

  7. Abdominal obesity and gastroesophageal cancer risk: systematic review and meta-analysis of prospective studies.

    PubMed

    Du, Xuan; Hidayat, Khemayanto; Shi, Bi-Min

    2017-06-30

    To systematically and quantitatively review the relation of abdominal obesity, as measured by waist circumference (WC) and waist to hip ratio (WHR), to total gastroesophageal cancer, gastric cancer (GC), and esophageal cancer. PubMed and Web of Science databases were searched for studies assessing the association between abdominal obesity and gastroesophageal cancer (GC and/or esophageal cancer) up to August 2016. A random-effect model was used to calculate the summary relative risks (RRs) and 95% confidence intervals (CIs). Seven prospective cohort studies - one publication included two separate cohorts - from six publications were included in the final analysis. A total of 2130 gastroesophageal cancer cases diagnosed amongst 913182 participants. Higher WC and WHR were significantly associated with increased risk of total gastroesophageal cancer (WC: RR 1.68, 95% CI: 1.38, 2.04; WHR: RR 1.49, 95% CI: 1.19, 1.88), GC (WC: RR 1.48, 95% CI: 1.24, 1.78; WHR: 1.33, 95% CI: 1.04, 1.70), and esophageal cancer (WC: RR 2.06, 95% CI: 1.30, 3.24; WHR: RR 1.99, 95% CI: 1.05, 3.75).Findings from our subgroup analyses showed non-significant positive associations between gastric non-cardia adenocarcinoma (GNCA) and both measures of abdominal adiposity, while gastric cardia adenocarcinoma (GCA) was positively associated with WC but not with WHR. On analysis restricted to studies that adjusted for body mass index (BMI), WC was positively associated with GC and esophageal cancer, whereas WHR was positively associated with risk of GC only. Although limited, the findings from our meta-analysis suggest the potential role of abdominal obesity in the etiology of gastric and esophageal cancers. © 2017 The Author(s).

  8. Abdominal obesity and gastroesophageal cancer risk: systematic review and meta-analysis of prospective studies

    PubMed Central

    Du, Xuan; Hidayat, Khemayanto

    2017-01-01

    To systematically and quantitatively review the relation of abdominal obesity, as measured by waist circumference (WC) and waist to hip ratio (WHR), to total gastroesophageal cancer, gastric cancer (GC), and esophageal cancer. PubMed and Web of Science databases were searched for studies assessing the association between abdominal obesity and gastroesophageal cancer (GC and/or esophageal cancer) up to August 2016. A random-effect model was used to calculate the summary relative risks (RRs) and 95% confidence intervals (CIs). Seven prospective cohort studies – one publication included two separate cohorts – from six publications were included in the final analysis. A total of 2130 gastroesophageal cancer cases diagnosed amongst 913182 participants. Higher WC and WHR were significantly associated with increased risk of total gastroesophageal cancer (WC: RR 1.68, 95% CI: 1.38, 2.04; WHR: RR 1.49, 95% CI: 1.19, 1.88), GC (WC: RR 1.48, 95% CI: 1.24, 1.78; WHR: 1.33, 95% CI: 1.04, 1.70), and esophageal cancer (WC: RR 2.06, 95% CI: 1.30, 3.24; WHR: RR 1.99, 95% CI: 1.05, 3.75).Findings from our subgroup analyses showed non-significant positive associations between gastric non-cardia adenocarcinoma (GNCA) and both measures of abdominal adiposity, while gastric cardia adenocarcinoma (GCA) was positively associated with WC but not with WHR. On analysis restricted to studies that adjusted for body mass index (BMI), WC was positively associated with GC and esophageal cancer, whereas WHR was positively associated with risk of GC only. Although limited, the findings from our meta-analysis suggest the potential role of abdominal obesity in the etiology of gastric and esophageal cancers. PMID:28336766

  9. Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance.

    PubMed

    Almuraikhy, Shamma; Kafienah, Wael; Bashah, Moataz; Diboun, Ilhame; Jaganjac, Morana; Al-Khelaifi, Fatima; Abdesselem, Houari; Mazloum, Nayef A; Alsayrafi, Mohammed; Mohamed-Ali, Vidya; Elrayess, Mohamed A

    2016-11-01

    A subset of obese individuals remains insulin sensitive by mechanisms as yet unclear. The hypothesis that maintenance of normal subcutaneous (SC) adipogenesis accounts, at least partially, for this protective phenotype and whether it can be abrogated by chronic exposure to IL-6 was investigated. Adipose tissue biopsies were collected from insulin-sensitive (IS) and insulin-resistant (IR) individuals undergoing weight-reduction surgery. Adipocyte size, pre-adipocyte proportion of stromal vascular fraction (SVF)-derived cells, adipogenic capacity and gene expression profiles of isolated pre-adipocytes were determined, along with local in vitro IL-6 secretion. Adipogenic capacity was further assessed in response to exogenous IL-6 application. Despite being equally obese, IR individuals had significantly lower plasma leptin and adiponectin levels and higher IL-6 levels compared with age-matched IS counterparts. Elevated systemic IL-6 in IR individuals was associated with hyperplasia of adipose tissue-derived SVF cells, despite higher frequency of hypertrophied adipocytes. SC pre-adipocytes from these tissues exhibited lower adipogenic capacity accompanied by downregulation of PPARγ (also known as PPARG) and CEBPα (also known as CEBPA) and upregulation of GATA3 expression. Impaired adipogenesis in IR individuals was further associated with increased adipose secretion of IL-6. Treatment of IS-derived SC pre-adipocytes with IL-6 reduced their adipogenic capacity to levels of the IR group. Obesity-associated insulin resistance is marked by impaired SC adipogenesis, mediated, at least in a subset of individuals, by elevated local levels of IL-6. Understanding the molecular mechanisms underlying reduced adipogenic capacity in IR individuals could help target appropriate therapeutic strategies aimed at those at greatest risk of insulin resistance and type 2 diabetes mellitus.

  10. The Effects of Combined Exercise on Health-Related Fitness, Endotoxin, and Immune Function of Postmenopausal Women with Abdominal Obesity.

    PubMed

    Park, Sung-Mo; Kwak, Yi-Sub; Ji, Jin-Goo

    2015-01-01

    This study was conducted to examine the effects of combined exercise on health-related fitness, endotoxin concentrations, and immune functions of postmenopausal women with abdominal obesity. 20 voluntary participants were recruited and they were randomly allocated to the combined exercise group (n = 10) or the control group (n = 10). Visceral obesity was defined as a visceral-to-subcutaneous fat ratio ≥ 0.4 based on computed tomography (CT) results. Body composition, exercise stress testing, fitness measurement, CT scan, and blood variables were analyzed to elucidate the effects of combined exercise. The SPSS Statistics 18.0 program was used to calculate means and standard deviations for all variables. Significant differences between the exercise group and control group were determined with 2-way ANOVA and paired t-tests. The exercise group's abdominal obesity was mitigated due to visceral fat reduction; grip strength, push-ups, and oxygen uptake per weight improved; and HDL-C and IgA level also increased, while TNF-α, CD14, and endotoxin levels decreased. Lowered TNF-α after exercise might have an important role in the obesity reduction. Therefore, we can conclude that combined exercise is effective in mitigating abdominal obesity, preventing metabolic diseases, and enhancing immune function.

  11. Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness

    PubMed Central

    Stuart, Charles A.; Lee, Michelle L.; South, Mark A.; Howell, Mary E.A.; Cartwright, Brian M.; Ramsey, Michael W.; Stone, Michael H.

    2016-01-01

    Only half of pre-diabetic, subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pre-training characteristics favoring a positive response to exercise training. Thirty non-diabetic, subjects who are obese volunteered for eight weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and GLUT4 expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pre-training baseline. PMID:27379957

  12. Obesity and Dyslipidemia in South Asians

    PubMed Central

    Misra, Anoop; Shrivastava, Usha

    2013-01-01

    Obesity and dyslipidemia are emerging as major public health challenges in South Asian countries. The prevalence of obesity is more in urban areas than rural, and women are more affected than men. Further, obesity in childhood and adolescents is rising rapidly. Obesity in South Asians has characteristic features: high prevalence of abdominal obesity, with more intra-abdominal and truncal subcutaneous adiposity than white Caucasians. In addition, there is greater accumulation of fat at “ectopic” sites, namely the liver and skeletal muscles. All these features lead to higher magnitude of insulin resistance, and its concomitant metabolic disorders (the metabolic syndrome) including atherogenic dyslipidemia. Because of the occurrence of type 2 diabetes, dyslipidemia and other cardiovascular morbidities at a lower range of body mass index (BMI) and waist circumference (WC), it is proposed that cut-offs for both measures of obesity should be lower (BMI 23–24.9 kg/m2 for overweight and ≥25 kg/m2 for obesity, WC ≥80 cm for women and ≥90 cm for men for abdominal obesity) for South Asians, and a consensus guideline for these revised measures has been developed for Asian Indians. Increasing obesity and dyslipidemia in South Asians is primarily driven by nutrition, lifestyle and demographic transitions, increasingly faulty diets and physical inactivity, in the background of genetic predisposition. Dietary guidelines for prevention of obesity and diabetes, and physical activity guidelines for Asian Indians are now available. Intervention programs with emphasis on improving knowledge, attitude and practices regarding healthy nutrition, physical activity and stress management need to be implemented. Evidence for successful intervention program for prevention of childhood obesity and for prevention of diabetes is available for Asian Indians, and could be applied to all South Asian countries with similar cultural and lifestyle profiles. Finally, more research on

  13. Dependence of Cardiac Systolic Function on Elevated Fatty Acid Availability in Obese, Insulin-Resistant Rats.

    PubMed

    Smith, Wayne; Norton, Gavin R; Woodiwiss, Angela J; Lochner, Amanda; du Toit, Eugene F

    2016-07-01

    Clinical data advocating an adverse effect of obesity on left ventricular (LV) systolic function independent of comorbidities is controversial. We hypothesized that in obesity with prediabetic insulin resistance, circulating fatty acids (FAs) become a valuable fuel source in the maintenance of normal systolic function. Male Wistar rats were fed a high caloric diet for 32 weeks to induce obesity. Myocardial LV systolic function was assessed using echocardiography and isolated heart preparations. Aortic output was reduced in obese rat hearts over a range of filling pressures (for example: 15 cmH2O, obese: 32.6 ± 1.2 ml/min vs control: 46.2 ± 0.9 ml/min, P < .05) when perfused with glucose alone. Similarly, the slope of the LV end-systolic pressure-volume relationship decreased, and there was a right shift in the LV end-systolic stress-strain relationship as determined in Langendorff perfused, isovolumic rat heart preparations in the presence of isoproterenol (10(-8)M) (LV systolic stress-strain relationship and a reduced load-independent intrinsic systolic myocardial function, obese: 791 ± 62 g/cm(2) vs control: 1186 ± 74 g/cm(2), P < .01). The addition of insulin to the perfusion buffer improved aortic output, whereas the addition of FAs completely normalized aortic output. LV function was maintained in obese animals in vivo during an inotropic challenge. Elevated circulating FA levels may be important to maintain myocardial systolic function in the initial stages of obesity and insulin resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Mediterranean dietary pattern in pregnant women and offspring risk of overweight and abdominal obesity in early childhood: the INMA birth cohort study.

    PubMed

    Fernández-Barrés, S; Romaguera, D; Valvi, D; Martínez, D; Vioque, J; Navarrete-Muñoz, E M; Amiano, P; Gonzalez-Palacios, S; Guxens, M; Pereda, E; Riaño, I; Tardón, A; Iñiguez, C; Arija, V; Sunyer, J; Vrijheid, M

    2016-12-01

    Animal models have suggested that maternal diet quality may reduce offspring obesity risk regardless of maternal body weight; however, evidence from human studies is scarce. The aim of this study was to evaluate associations between adherence to the Mediterranean diet (MD) during pregnancy and childhood overweight and abdominal obesity risk at 4 years of age. We analysed 1827 mother-child pairs from the Spanish 'Infancia y Medio Ambiente' cohort study, recruited between 2003 and 2008. Diet was assessed during pregnancy using a food frequency questionnaire and MD adherence by the relative Mediterranean diet score (rMED). Overweight (including obesity) was defined as an age-specific and sex-specific body mass index ≥85th percentile (World Health Organization referent), and abdominal obesity as a waist circumference (WC) >90th percentile. Multivariate adjusted linear and logistic regression models were used to evaluate associations between pregnancy rMED and offspring overweight and abdominal obesity. There was no association between rMED and body mass index z-score, whereas there was a significant association between higher adherence to MD and lower WC (β of high vs. low rMED: -0.62 cm; 95% confidence interval: -1.10, -0.14 cm, P for trend = 0.009). Pregnancy adherence to the MD was not associated with childhood overweight risk, but it was associated with lower WC, a marker of abdominal obesity. © 2016 World Obesity Federation.

  15. The Gradual Shift of Overweight, Obesity, and Abdominal Obesity Towards the Poor in a Multi-ethnic Developing Country: Findings From the Malaysian National Health and Morbidity Surveys

    PubMed Central

    Mariapun, Jeevitha; Ng, Chiu-Wan; Hairi, Noran N.

    2018-01-01

    Background Economic development is known to shift the distribution of obesity from the socioeconomically more advantaged to the less advantaged. We assessed the socioeconomic trends in overweight, obesity, and abdominal obesity across a period of significant economic growth. Methods We used the Malaysian National Health and Morbidity Survey data sets for the years 1996, 2006, and 2011 to analyze the trends among adults aged 30 years and above. The World Health Organization’s Asian body mass index cut-off points of ≥23.0 kg/m2 and ≥27.5 kg/m2 were used to define overweight and obesity, respectively. Abdominal obesity was defined as having a waist circumference of ≥90 cm for men and ≥80 cm for women. Household per-capita income was used as a measure of socioeconomic position. As a summary measure of inequality, we computed the concentration index. Results Women in Peninsular Malaysia demonstrated patterns that were similar to that of developed countries in which the distributions for overweight, obesity, and abdominal obesity became concentrated among the poor. For women in East Malaysia, distributions became neither concentrated among the rich nor poor, while distributions for men were still concentrated among the rich. Chinese women, particularly from the richest quintile, had the lowest rates and lowest increase in overweight and obesity. All distributions of Chinese women were concentrated among the poor. The distributions of Malay men were still concentrated among the rich, while distributions for Chinese and Indian men and Malay and Indian women were neither concentrated among the rich nor poor. Conclusion As the country continues to progress, increasing risks of overweight and obesity among the socioeconomically less advantaged is expected. PMID:29657257

  16. Programming of Fetal Insulin Resistance in Pregnancies with Maternal Obesity by ER Stress and Inflammation

    PubMed Central

    Sáez, Pablo J.; Villalobos-Labra, Roberto; Farías-Jofré, Marcelo

    2014-01-01

    The global epidemics of obesity during pregnancy and excessive gestational weight gain (GWG) are major public health problems worldwide. Obesity and excessive GWG are related to several maternal and fetal complications, including diabetes (pregestational and gestational diabetes) and intrauterine programming of insulin resistance (IR). Maternal obesity (MO) and neonatal IR are associated with long-term development of obesity, diabetes mellitus, and increased global cardiovascular risk in the offspring. Multiple mechanisms of insulin signaling pathway impairment have been described in obese individuals, involving complex interactions of chronically elevated inflammatory mediators, adipokines, and the critical role of the endoplasmic reticulum (ER) stress-dependent unfolded protein response (UPR). However, the underlying cellular processes linking MO and IR in the offspring have not been fully elucidated. Here, we summarize the state-of-the-art evidence supporting the possibility that adverse metabolic postnatal outcomes such as IR in the offspring of pregnancies with MO and/or excessive GWG may be related to intrauterine activation of ER stress response. PMID:25093191

  17. Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

    PubMed

    Kowalska, Irina; Straczkowski, Marek; Nikolajuk, Agnieszka; Adamska, Agnieszka; Karczewska-Kupczewska, Monika; Otziomek, Elzbieta; Wolczynski, Slawomir; Gorska, Maria

    2007-07-01

    Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.

  18. Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance.

    PubMed

    Van Name, Michelle; Giannini, Cosimo; Santoro, Nicola; Jastreboff, Ania M; Kubat, Jessica; Li, Fangyong; Kursawe, Romy; Savoye, Mary; Duran, Elvira; Dziura, James; Sinha, Rajita; Sherwin, Robert S; Cline, Gary; Caprio, Sonia

    2015-03-01

    Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity. Adolescents were divided into lean (n = 14), obese insulin sensitive (n = 12) (OIS), and obese insulin resistant (n = 15) (OIR). In a double-blind, cross-over design, subjects drank 75 g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes. Baseline acyl-ghrelin was highest in lean and lowest in OIR (P = 0.02). After glucose ingestion, acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR (vs. lean, P = 0.03). Suppression differences were more pronounced after fructose (lean vs. OIS, P = 0.008, lean vs. OIR, P < 0.001). OIS became significantly hungrier after fructose (P = 0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose. Compared with lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating. © 2015 The Obesity Society.

  19. Physical Training Improves Insulin Resistance Syndrome Markers in Obese Adolescents.

    ERIC Educational Resources Information Center

    Kang, Hyun-Sik; Gutin, Bernard; Barbeau, Paule; Owens, Scott; Lemmon, Christian R.; Allison, Jerry; Litaker, Mark S.; Le, Ngoc-Anh

    2002-01-01

    Tested the hypothesis that physical training (PT), especially high-intensity PT, would favorably affect components of the insulin resistance syndrome (IRS) in obese adolescents. Data on teens randomized into lifestyle education (LSE) alone, LSE plus moderate -intensity PT, and LSE plus high-intensity PT indicated that PT, especially high-intensity…

  20. Evaluating the association of APOA2 polymorphism with insulin resistance in adolescents.

    PubMed

    Zaki, Moushira Erfan; Amr, Khalda Sayed; Abdel-Hamid, Mohamed

    2014-12-01

    265T>C SNP in the APOA-II gene promoter may be associated with obesity risk and insulin resistance (IR). This study aims to analyze the association between the APOA2 - 265T>C SNP and risk for obesity and IR in adolescents. The study was conducted on 500 adolescents. They were 240 obese and 260 non-obese individuals, aged 16-21 years old. Their mean age was 18.25 ± 2.54 years. Variables examined body weight, height, waist circumference (WC), systolic and diastolic blood pressure (BP), body fat percentage (BF%), and abdominal visceral fat layer. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used as a biomarker for IR. BF% was assessed by body composition analyzer and abdominal visceral fat thickness was determined by ultrasonography. The APOA2 - 265T>C polymorphism genotype was analyzed by PCR amplification of a 273-bp fragment. Genotype frequencies were in Hardy-Weinberg equilibrium. The frequency of the mutant C allele was significantly higher in obese cases than non-obese cases. After multivariate adjustment, waist, BF%, visceral adipose layer and HOMA-IR were significantly higher in homozygous allele CC carriers than TT + TC carriers. Homozygous individuals for the CC allele had statistically higher values of energy intake, total fat (g/day) and saturated fat (SATFAT) than carriers of the T allele. Homozygous individuals for the C allele had higher obesity risk than carriers of the T allele and had elevated levels of visceral adipose tissue. Moreover, the present study shows that the CC polymorphism is associated with the development of IR [OR 1.89 (1.35-2.91), P = .012] and remains significant after adjusting for gender, age and body mass index.

  1. Evaluating the association of APOA2 polymorphism with insulin resistance in adolescents

    PubMed Central

    Zaki, Moushira Erfan; Amr, Khalda Sayed; Abdel-Hamid, Mohamed

    2014-01-01

    Background 265T>C SNP in the APOA-II gene promoter may be associated with obesity risk and insulin resistance (IR). This study aims to analyze the association between the APOA2 − 265T>C SNP and risk for obesity and IR in adolescents. Material and methods The study was conducted on 500 adolescents. They were 240 obese and 260 non-obese individuals, aged 16–21 years old. Their mean age was 18.25 ± 2.54 years. Variables examined body weight, height, waist circumference (WC), systolic and diastolic blood pressure (BP), body fat percentage (BF%), and abdominal visceral fat layer. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used as a biomarker for IR. BF% was assessed by body composition analyzer and abdominal visceral fat thickness was determined by ultrasonography. The APOA2 − 265T>C polymorphism genotype was analyzed by PCR amplification of a 273-bp fragment. Results Genotype frequencies were in Hardy–Weinberg equilibrium. The frequency of the mutant C allele was significantly higher in obese cases than non-obese cases. After multivariate adjustment, waist, BF%, visceral adipose layer and HOMA-IR were significantly higher in homozygous allele CC carriers than TT + TC carriers. Homozygous individuals for the CC allele had statistically higher values of energy intake, total fat (g/day) and saturated fat (SATFAT) than carriers of the T allele. Conclusions Homozygous individuals for the C allele had higher obesity risk than carriers of the T allele and had elevated levels of visceral adipose tissue. Moreover, the present study shows that the CC polymorphism is associated with the development of IR [OR 1.89 (1.35–2.91), P = .012] and remains significant after adjusting for gender, age and body mass index. PMID:25606421

  2. Uncoupling of Obesity from Insulin Resistance Through a Targeted Mutation in aP2, the Adipocyte Fatty Acid Binding Protein

    NASA Astrophysics Data System (ADS)

    Hotamisligil, Gokhan S.; Johnson, Randall S.; Distel, Robert J.; Ellis, Ramsey; Papaioannou, Virginia E.; Spiegelman, Bruce M.

    1996-11-01

    Fatty acid binding proteins (FABPs) are small cytoplasmic proteins that are expressed in a highly tissue-specific manner and bind to fatty acids such as oleic and retinoic acid. Mice with a null mutation in aP2, the gene encoding the adipocyte FABP, were developmentally and metabolically normal. The aP2-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also unlike their obese wild-type counterparts, obese aP2-/- animals failed to express in adipose tissue tumor necrosis factor-α (TNF-α), a molecule implicated in obesity-related insulin resistance. These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-α.

  3. Smad3 Deficiency in Mice Protects Against Insulin Resistance and Obesity Induced by a High-Fat Diet

    PubMed Central

    Tan, Chek Kun; Leuenberger, Nicolas; Tan, Ming Jie; Yan, Yew Wai; Chen, Yinghui; Kambadur, Ravi; Wahli, Walter; Tan, Nguan Soon

    2011-01-01

    OBJECTIVE Obesity and associated pathologies are major global health problems. Transforming growth factor-β/Smad3 signaling has been implicated in various metabolic processes, including adipogenesis, insulin expression, and pancreatic β-cell function. However, the systemic effects of Smad3 deficiency on adiposity and insulin resistance in vivo remain elusive. This study investigated the effects of Smad3 deficiency on whole-body glucose and lipid homeostasis and its contribution to the development of obesity and type 2 diabetes. RESEARCH DESIGN AND METHODS We compared various metabolic profiles of Smad3-knockout and wild-type mice. We also determined the mechanism by which Smad3 deficiency affects the expression of genes involved in adipogenesis and metabolism. Mice were then challenged with a high-fat diet to study the impact of Smad3 deficiency on the development of obesity and insulin resistance. RESULTS Smad3-knockout mice exhibited diminished adiposity with improved glucose tolerance and insulin sensitivity. Chromatin immunoprecipitation assay revealed that Smad3 deficiency increased CCAAT/enhancer-binding protein β-C/EBP homologous protein 10 interaction and exerted a differential regulation on proliferator-activated receptor β/δ and proliferator-activated receptor γ expression in adipocytes. Focused gene expression profiling revealed an altered expression of genes involved in adipogenesis, lipid accumulation, and fatty acid β-oxidation, indicative of altered adipose physiology. Despite reduced physical activity with no modification in food intake, these mutant mice were resistant to obesity and insulin resistance induced by a high-fat diet. CONCLUSIONS Smad3 is a multifaceted regulator in adipose physiology and the pathogenesis of obesity and type 2 diabetes, suggesting that Smad3 may be a potential target for the treatment of obesity and its associated disorders. PMID:21270259

  4. The insulin effect on cerebrocortical theta activity is associated with serum concentrations of saturated nonesterified Fatty acids.

    PubMed

    Tschritter, Otto; Preissl, Hubert; Hennige, Anita M; Sartorius, Tina; Grichisch, Yuko; Stefan, Norbert; Guthoff, Martina; Düsing, Stephan; Machann, Jürgen; Schleicher, Erwin; Cegan, Alexander; Birbaumer, Niels; Fritsche, Andreas; Häring, Hans-Ulrich

    2009-11-01

    Insulin action in the brain contributes to adequate regulation of body weight, neuronal survival, and suppression of endogenous glucose production. We previously demonstrated by magnetoencephalography in lean humans that insulin stimulates activity in beta and theta frequency bands, whereas this effect was abolished in obese individuals. The present study aims to define metabolic signals associated with the suppression of the cerebrocortical response in obese humans. We determined insulin-mediated modulation of spontaneous cerebrocortical activity by magnetoencephalography during a hyperinsulinemic euglycemic clamp and related it to measures of ectopic fat deposition and mediators of peripheral insulin resistance. Visceral fat mass and intrahepatic lipid content were quantified by magnetic resonance imaging and spectroscopy. Multiple regression analysis was used to analyze associations of cerebrocortical insulin sensitivity and metabolic markers related to obesity. Forty-nine healthy, nondiabetic humans participated in the study. In a multiple regression, insulin-mediated stimulation of theta activity was negatively correlated to body mass index, visceral fat mass, and intrahepatic lipid content. Although fasting saturated nonesterified fatty acids mediated the correlations of theta activity with abdominal and intrahepatic lipid stores, adipocytokines displayed no independent correlation with insulin-mediated cortical activity in the theta frequency band. Thus, insulin action at the level of cerebrocortical activity in the brain is diminished in the presence of elevated levels of saturated nonesterified fatty acids.

  5. [Cyanidin-3-glucoside attenuates body weight gain, serum lipid concentrations and insulin resistance in high-fat diet-induced obese rats].

    PubMed

    Yu, Ren-Qiang; Wu, Xiao-You; Zhou, Xiang; Zhu, Jing; Ma, Lu-Yi

    2014-05-01

    Cyanidin-3-glucoside (C3G) is the main active ingredient of anthocyanidin. This study aimed to evaluate the effects of C3G on body weight gain, visceral adiposity, lipid profiles and insulin resistance in high-fat diet-induced obese rats. Thirty male Sprague-Dawley rats were randomly divided into a control group (n=8) and a high fat diet group (n=22), and were fed with standard diet or high fat diet. Five weeks later, 17 high-fat diet-induced obese rats were randomly given C3G [100 mg/(kg·d)] or normal saline via intragastric administration for 5 weeks. Five weeks later, body weight, visceral adiposity and food intake were measured. Blood samples were collected for detecting fasting glucose, serum insulin, lipid profiles and adiponectin. Insulin resistance index, atherosclerosis index and average feed efficiency ratio were calculated. C3G supplementation markedly decreased body weight, visceral adiposity, average feed efficiency ratio, triglyceride, total cholesterol, low density lipoprotein cholesterol, fasting glucose, serum insulin, insulin resistance index and atherosclerosis index in high-fat diet-induced obese rats. C3G supplementation normalized serum adiponectin and high density lipoprotein cholesterol levels in high-fat diet-induced obese rats. Cyanidin-3-glucoside can reduce body weight gain, and attenuate obesity-associated dyslipidemia and insulin resistance in high-fat diet-fed rats via up-regulating serum adiponectin level.

  6. Zinc-α2-glycoprotein expression in adipose tissue of obese postmenopausal women before and after weight loss and exercise + weight loss.

    PubMed

    Ge, Shealinna; Ryan, Alice S

    2014-08-01

    Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the regulation of adipose tissue metabolism due to its negative association with obesity and insulin resistance. The purpose of this study is to investigate the relationships between adipose tissue ZAG expression and central obesity, and the effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX + WL) on ZAG expression. A six-month, longitudinal study of 33 healthy, overweight or obese postmenopausal women (BMI: 25-46 kg/m(2)) was conducted. Abdominal and gluteal adipose tissue samples were obtained before and after AEX + WL (n = 17) and WL (n = 16). ZAG expression was determined by RT-PCR. Prior to interventions, abdominal ZAG expression was negatively correlated with visceral fat (r = -0.50, P < 0.005), sagittal diameter (r = -0.42, P < 0.05), and positively related to VO(2)max (r = 0.37, P < 0.05). Gluteal ZAG expression was negatively correlated with weight, fat-free mass, visceral fat, resting metabolic rate, and fasting insulin (r = -0.39 to -0.50, all P < 0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after AEX + WL and 11% after WL. Gluteal ZAG mRNA levels also did not change significantly with AEX + WL and WL. Abdominal ZAG expression may be important in central fat accumulation and fitness but only modestly increase (nonsignificantly) with weight reduction alone or with aerobic training in obese postmenopausal women. Published by Elsevier Inc.

  7. Serum resistin correlates with central obesity but weakly with insulin resistance in Chinese children and adolescents.

    PubMed

    Li, M; Fisette, A; Zhao, X-Y; Deng, J-Y; Mi, J; Cianflone, K

    2009-04-01

    Resistin has been linked with obesity and hypothesized as a potential marker of insulin resistance in addition to being linked with acute inflammation. However, these links are still highly controversial in humans. Our goal was to examine resistin levels in relation to obesity, insulin resistance and inflammation markers in a large population of Asian children and adolescents. Children and adolescents (n=3472) aged 6-18 years, boys (n=1765) and girls (n=1707), were assessed for body size parameters, pubertal development, blood lipids, glucose, insulin, resistin, C-reactive protein (CRP), adiponectin and complement C3 (C3) levels. Resistin increased with central obesity in both genders but not with simple adiposity in boys. Several markers associated with central obesity correlated in a gender-specific fashion with plasma resistin. Waist circumference, fat-mass percentage, waist-to-height ratio and body mass index (BMI) positively correlated with resistin in both genders. Blood lipids such as triglycerides, nonesterified fatty acids (NEFA) and low-density lipoprotein cholesterol, diastolic and systolic blood pressure correlated positively with resistin in boys. NEFA, high-density lipoprotein cholesterol (negatively) and inflammation markers, such as CRP and C3, positively correlated with resistin in girls. There was no correlation between resistin and adiponectin, and no association of adiponectin with resistin quintiles in either boys or girls. In both boys and girls, resistin tended to decrease with age, with girls having higher levels than boys. Few indices of insulin resistance were linked with plasma resistin in either gender. In this population, plasma resistin levels are a weak biochemical marker of metabolic dysfunction defined by central obesity, adiposity and inflammation and does not predict insulin resistance. Only a small proportion of resistin variation can be explained by factors related to metabolic syndrome, suggesting that resistin is not strongly

  8. Fitness, adiposopathy, and adiposity are independent predictors of insulin sensitivity in middle-aged men without diabetes.

    PubMed

    Huth, Claire; Pigeon, Étienne; Riou, Marie-Ève; St-Onge, Josée; Arguin, Hélène; Couillard, Erick; Dubois, Marie-Julie; Marette, André; Tremblay, Angelo; Weisnagel, S John; Lacaille, Michel; Mauriège, Pascale; Joanisse, Denis R

    2016-09-01

    Adiposopathy, or sick fat, refers to adipose tissue dysfunction that can lead to several complications such as dyslipidemia, insulin resistance, and hyperglycemia. The relative contribution of adiposopathy in predicting insulin resistance remains unclear. We investigated the relationship between adiposopathy, as assessed as a low plasma adiponectin/leptin ratio, with anthropometry, body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), inflammation, and fitness level (ergocycle VO2max, mL/kgFFM/min) in 53 men (aged 34-53 years) from four groups: sedentary controls without obesity (body mass index [BMI] <25 kg/m(2)), sedentary with obesity (BMI > 30 kg/m(2)), sedentary with obesity and glucose intolerance, and endurance trained active without obesity. The adiponectin/leptin ratio was the highest in trained men (4.75 ± 0.82) and the lowest in glucose intolerant subjects with obesity (0.27 ± 0.06; ANOVA p < 0.0001) indicating increased adiposopathy in those with obesity. The ratio was negatively associated with adiposity (e.g., waist circumference, r = -0.59, p < 0.01) and positively associated with VO2max (r = 0.67, p < 0.01) and insulin sensitivity (M/I, r = 0.73, p < 0.01). Multiple regression analysis revealed fitness as the strongest independent predictor of insulin sensitivity (partial R (2) = 0.61). While adiposopathy was also an independent and significant contributor (partial R (2) = 0.10), waist circumference added little power to the model (partial R (2) = 0.024). All three variables remained significant independent predictors when trained subjects were excluded from the model. Plasma lipids were not retained in the model. We conclude that low fitness, adiposopathy, as well as adiposity (and in particular abdominal obesity) are independent contributors to insulin resistance in men without diabetes.

  9. Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant state.

    PubMed

    Adams, Sean H

    2011-11-01

    Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well known and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. Although the central role of proper blood sugar control in maintaining metabolic health is well established, recent developments have begun to shed light on associations between compromised insulin action [obesity, prediabetes, and type 2 diabetes mellitus (T2DM)] and altered intermediary metabolism of fats and amino acids. For amino acids, changes in blood concentrations of select essential amino acids and their derivatives, in particular BCAA, sulfur amino acids, tyrosine, and phenylalanine, are apparent with obesity and insulin resistance, often before the onset of clinically diagnosed T2DM. This review provides an overview of these changes and places recent observations from metabolomics research into the context of historical reports in the areas of biochemistry and nutritional biology. Based on this synthesis, a model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+).

  10. [Evaluate the Efficacy of Electroacupuncture Therapy on Abdominal Fat in Obese Women by Using Magnetic Resonance Imaging].

    PubMed

    Lei, Hong; Chen, Xiao; Hu, Dong-Gang; Chen, Yu-Ting; Feng, Li-Cheng; Chen, Zhen-Yan; Li, Fang

    2016-10-25

    To evaluate the efficacy of electroacupuncture (EA) therapy on abdominal fat in obese women by using magnetic resonance imaging(MRI). Thirty abdominal obesity women patients were randomly divided into control group ( n =15) and EA group ( n =15). The obesity patients of the control group did not receive any treatment for weight reduction, and those of the EA group were treated by EA stimulation of bilateral Neiting (ST 44), Fenglong (ST 40), Zusanli (ST 36), Huaroumen (ST 24), Tianshu (ST 25), Wailing (ST 26), Shuidao (ST 28), Fujie (SP 14), Daheng (SP 13), etc. for 25 min, once every other day, 3 times per week for 3 months. The patient's body weight, height, waist circumference (WC) were mea-sured with different devices, and the body mass index (BMI) was calculated, and the subcutaneous adipose tissue thickness at the inferior edges of L 4 , L 5 and S 3 and the superior edge of the pubic symphysis and the total abdominal fat volume between the L 4 and S 3 levels were detected using MRI systems before and after the treatment. The effects of the EA group were significantly superior to those of the control group in lowering difference values (between pre- and post-treatment) of BMI, WC and subcutaneous adipose tissue thickness at the levels of the inferior edges of L 4 , L 5 , S 3 and the superior edge of the pubic symphysis(all P <0.01)and in reducing total abdominal fat volume between L 4 and S 3 (all P <0.01). After the treatment, the subcutaneous adipose tissue thickness at the superior edge of the pubic symphysis ( P <0.01) and the total abdominal fat volume between L 4 and S 3 ( P <0.05) were significantly decreased in the EA group compared to pre-treatment. There were no significant differences between post- and pre-treatment in BMI, WC, subcutaneous adipose tissue thickness at the levels of the L 4 , L 5 and S 3 in both EA and control groups and in the subcutaneous adipose tissue thickness at the level of the superior edge of the pubic symphysis and the

  11. Effects of combined physical activity and dietary intervention on obesity and metabolic parameters in adults with abdominal obesity.

    PubMed

    Soon, Heng Kiang; Saad, Hazizi Abu; Taib, Mohd Nasir Mohd; Rahman, Hejar Abd; Mun, Chan Yoke

    2013-03-01

    A twelve-week controlled intervention trial was carried out to evaluate the effects of combined physical activity and dietary intervention on obesity and metabolic risk factors among employees of Universiti Putra Malaysia. Participants consisted of adults aged 25-55 years with no reported chronic diseases but with abdominal obesity. They were assigned to either a combined physical activity and dietary intervention group or a control group. The final sample consisted of 56 participants, with an equal number of 28 for each study group. No significant group effect was observed for any variable except for hip circumference (HC) and fasting plasma glucose (FPG). There was a significant increase in HC (p=0.007) and reduction in FPG (p=0.02) in the intervention group compared to the control group. In the intervention group, HC (p=0.002), triglycerides (TG) (p=0.0001), total cholesterol (TC) (p=0.0001), LDL cholesterol (LDLC) (p=0.0001) and FPG (p=0.005) were significantly reduced, while waist circumference (WC) (p=0.025) and the waist-to-hip ratio (WHR) (p=0.027) were significantly reduced in the control group. No significant change in steps/day or calorie intake'was observed in either group. Taken together, these data indicate that the combined physical activity and dietary intervention was not effective at improving diet or physical activity level. However, the intervention was effective in improving FPG among participants with abdominal obesity. The significant increase in HC in the interventions group warrants further study. These findings will be useful to further improve group-based intervention for the prevention and management of obesity.

  12. Identification of fatty acid binding protein 4 as an adipokine that regulates insulin secretion during obesity

    PubMed Central

    Wu, Lindsay E.; Samocha-Bonet, Dorit; Whitworth, P. Tess; Fazakerley, Daniel J.; Turner, Nigel; Biden, Trevor J.; James, David E.; Cantley, James

    2014-01-01

    A critical feature of obesity is enhanced insulin secretion from pancreatic β-cells, enabling the majority of individuals to maintain glycaemic control despite adiposity and insulin resistance. Surprisingly, the factors coordinating this adaptive β-cell response with adiposity have not been delineated. Here we show that fatty acid binding protein 4 (FABP4/aP2) is an adipokine released from adipocytes under obesogenic conditions, such as hypoxia, to augment insulin secretion. The insulinotropic action of FABP4 was identified using an in vitro system that recapitulates adipocyte to β-cell endocrine signalling, with glucose-stimulated insulin secretion (GSIS) as a functional readout, coupled with quantitative proteomics. Exogenous FABP4 potentiated GSIS in vitro and in vivo, and circulating FABP4 levels correlated with GSIS in humans. Insulin inhibited FABP4 release from adipocytes in vitro, in mice and in humans, consistent with feedback regulation. These data suggest that FABP4 and insulin form an endocrine loop coordinating the β-cell response to obesity. PMID:24944906

  13. Abdominal obesity and the metabolic syndrome: a surgeon's perspective.

    PubMed

    Mathieu, Patrick

    2008-09-01

    Over the past decade, a major shift in the clinical risk factors in the population undergoing a cardiac surgery has been observed. In the general population, an increasing prevalence of obesity has largely contributed to the development of cardiovascular disorders. Obesity is a heterogeneous condition in which body fat distribution largely determines metabolic perturbations. Consequently, individuals characterized by increased abdominal fat deposition and the so-called metabolic syndrome (MetS) have a higher risk of developing coronary artery disease. Recent studies have also emphasized that visceral obesity is a strong risk factor for the development of heart valve diseases. In fact, individuals characterized by visceral obesity and its metabolic consequences, such as the small dense low-density lipoprotein phenotype, have a faster progression rate of aortic stenosis, which is related to increased valvular inflammation. Furthermore, the degenerative process of implanted bioprostheses is increased in subjects with the MetS and/or diabetes, suggesting that a process akin to atherosclerosis could be involved in the failure of bioprostheses. In addition to being an important risk factor for the development of cardiovascular disorders, the MetS is increasing the operative mortality risk following coronary artery bypass graft surgery. Thus, recent evidence supports visceral obesity as a global risk factor that is affecting the development of many heart disorders, and that is also impacting negatively on the results of patients undergoing surgical treatment for cardiovascular diseases. In the present paper, recent concepts surrounding the MetS and its implications in various cardiovascular disorders are reviewed along with the clinical implications.

  14. Association of the Myostatin gene with obesity, abdominal obesity and low lean body mass and in non-diabetic Asian Indians in north India.

    PubMed

    Bhatt, Surya Prakash; Nigam, Priyanka; Misra, Anoop; Guleria, Randeep; Luthra, Kalpana; Jain, S K; Qadar Pasha, M A

    2012-01-01

    To determine the association of the A55T and K153R polymorphisms of the Myostatin gene with obesity, abdominal obesity and lean body mass (LBM) in Asian Indians in north India. A total of 335 subjects (238 men and 97 women) were assessed for anthropometry, % body fat (BF), LBM and biochemical parameters. Associations of Myostatin gene polymorphisms were evaluated with anthropometric, body composition and biochemical parameters. In A55T polymorphism, BMI (p=0.04), suprailiac skinfold (p=0.05), total skinfold (p=0.008), %BF (p=0.002) and total fat mass (p=0.003) were highest and % LBM (p=0.03) and total LBM (Kg) were lowest (p=0.04) in subjects with Thr/Thr genotype as compared to other genotypes. Association analysis of K153R polymorphism showed that subjects with R/R genotype had significantly higher BMI (p=0.05), waist circumference (p=0.04), %BF (p=0.04) and total fat mass (p=0.03), and lower %LBM (p=0.02) and total LBM [(Kg), (p=0.04)] as compared to other genotypes. Using a multivariate logistic regression model after adjusting for age and sex, subjects with Thr/Thr genotype of A55T showed high risk for high %BF (OR, 3.92, 95% Cl: 2.61-12.41), truncal subcutaneous adiposity (OR, 2.9, 95% Cl: 1.57-6.60)] and low LBM (OR, 0.64, 95% CI: 0.33-0.89) whereas R/R genotype of K153R showed high risk of obesity (BMI; OR, 3.2, 95% CI: 1.2-12.9; %BF, OR, 3.6, 95% CI: 1.04-12.4), abdominal obesity (OR, 2.12, 95% CI: 2.71-14.23) and low LBM (OR, 0.61, 95% CI: 0.29-0.79). We report that variants of Myostatin gene predispose to obesity, abdominal obesity and low lean body mass in Asian Indians in north India.

  15. The potential impact of animal protein intake on global and abdominal obesity: evidence from the Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) study.

    PubMed

    Alkerwi, Ala'a; Sauvageot, Nicolas; Buckley, Jonathan D; Donneau, Anne-Françoise; Albert, Adelin; Guillaume, Michèle; Crichton, Georgina E

    2015-07-01

    To examine the association of total animal protein intake and protein derived from different dietary sources (meat; fish and shellfish; eggs; milk products) with global and abdominal obesity among adults in Luxembourg. Binary logistic regression analysis was used to assess the relationship between animal protein intake (as a percentage of total energy intake) and global obesity (BMI ≥ 30.0 kg/m(2)) and abdominal obesity (waist circumference ≥ 102 cm for men and ≥ 88 cm for women), after controlling for potential confounders. Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) study. The study population was derived from a national cross-sectional stratified sample of 1152 individuals aged 18-69 years, recruited between November 2007 and January 2009. There was an independent positive association between total animal protein intake and both global (OR = 1.18; 95% CI 1.12, 1.25) and abdominal obesity (OR = 1.14; 95% CI 1.08, 1.20) after adjustment for age, gender, education, smoking, physical activity and intakes of total fat, carbohydrate, fibre, and fruit and vegetables. Protein intakes from meat, fish and shellfish were positively associated with global and abdominal obesity with further adjustment for vegetal protein and other sources of animal-derived protein (all P < 0.01). Protein derived from eggs or milk products was unrelated to global or abdominal obesity. Our findings suggest that protein derived from animal sources, in particular from meat, fish and shellfish, may be associated with increased risk of both global and abdominal obesity among presumably healthy adults in Luxembourg. These findings suggest that lower animal protein intakes may be important for maintenance of healthy body weight.

  16. Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.

    PubMed

    Cui, Ju; Pang, Jing; Lin, Ya-Jun; Gong, Huan; Wang, Zhen-He; Li, Yun-Xuan; Li, Jin; Wang, Zai; Jiang, Ping; Dai, Da-Peng; Li, Jian; Cai, Jian-Ping; Huang, Jian-Dong; Zhang, Tie-Mei

    2017-06-01

    Recent studies have shown that KIF5B (conventional kinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement of KIF5B in the homeostasis of metabolism. However, the in vivo physiologic function of KIF5B in adipose tissue remains to be determined. In this study, adipose-specific Kif5b knockout (F-K5bKO) mice were generated using the Cre-LoxP strategy. F-K5bKO mice had similar body weights to controls fed on a standard chow diet. However, F-K5bKO mice had hyperlipidemia and significant glucose intolerance and insulin resistance. Deletion of Kif5b aggravated the deleterious impact of a high-fat diet (HFD) on body weight gain, hepatosteatosis, glucose tolerance, and systematic insulin sensitivity. These changes were accompanied by impaired insulin signaling, decreased secretion of adiponectin, and increased serum levels of leptin and proinflammatory adipokines. F-K5bKO mice fed on an HFD exhibited lower energy expenditure and thermogenic dysfunction as a result of whitening of brown adipose due to decreased mitochondria biogenesis and down-regulation of key thermogenic gene expression. In conclusion, selective deletion of Kif5b in adipose tissue exacerbates HFD-induced obesity and its associated metabolic disorders, partly through a decrease in energy expenditure, dysregulation of adipokine secretion, and insulin signaling.-Cui, J., Pang, J., Lin, Y.-J., Gong, H., Wang, Z.-H., Li, Y.-X., Li, J., Wang, Z., Jiang, P., Dai, D.-P., Li, J., Cai, J.-P., Huang, J.-D., Zhang, T.-M. Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity. © FASEB.

  17. Compensation for obesity-induced insulin resistance in dogs: assessment of the effects of leptin, adiponectin, and glucagon-like peptide-1 using path analysis.

    PubMed

    Verkest, K R; Fleeman, L M; Morton, J M; Ishioka, K; Rand, J S

    2011-07-01

    The hormonal mediators of obesity-induced insulin resistance and compensatory hyperinsulinemia in dogs have not been identified. Plasma samples were obtained after a 24-h fast from 104 client-owned lean, overweight, and obese dogs. Plasma glucose and insulin concentrations were used to calculate insulin sensitivity and β-cell function with the use of the homeostasis model assessment (HOMA(insulin sensitivity) and HOMA(β-cell function), respectively). Path analysis with multivariable linear regression was used to identify whether fasting plasma leptin, adiponectin, or glucagon-like peptide-1 concentrations were associated with adiposity, insulin sensitivity, and basal insulin secretion. None of the dogs were hyperglycemic. In the final path model, adiposity was positively associated with leptin (P < 0.01) and glucagon-like peptide-1 (P = 0.04) concentrations. No significant total effect of adiposity on adiponectin in dogs (P = 0.24) was observed. If there is a direct effect of leptin on adiponectin, then our results indicate that this is a positive relationship, which at least partly counters a negative direct relationship between adiposity and adiponectin. Fasting plasma leptin concentration was directly negatively associated with fasting insulin sensitivity (P = 0.01) and positively associated with β-cell function (P < 0.01), but no direct association was observed between adiponectin concentration and either insulin sensitivity or β-cell function (P = 0.42 and 0.11, respectively). We conclude that dogs compensate effectively for obesity-induced insulin resistance. Fasting plasma leptin concentrations appear to be associated with obesity-associated changes in insulin sensitivity and compensatory hyperinsulinemia in naturally occurring obese dogs. Adiponectin does not appear to be involved in the pathophysiology of obesity-associated changes in insulin sensitivity. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Insulin resistance in prepubertal obese children correlates with sex-dependent early onset metabolomic alterations.

    PubMed

    Mastrangelo, A; Martos-Moreno, G Á; García, A; Barrios, V; Rupérez, F J; Chowen, J A; Barbas, C; Argente, J

    2016-10-01

    Insulin resistance (IR) is usually the first metabolic alteration diagnosed in obese children and the key risk factor for development of comorbidities. The factors determining whether or not IR develops as a result of excess body mass index (BMI) are still not completely understood. This study aimed to elucidate the mechanisms underpinning the predisposition toward hyperinsulinemia-related complications in obese children by using a metabolomic strategy that allows a profound interpretation of metabolic profiles potentially affected by IR. Serum from 60 prepubertal obese children (30 girls/30 boys, 50% IR and 50% non-IR in each group, but with similar BMIs) were analyzed by using liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry following an untargeted metabolomics approach. Validation was then performed on a group of 100 additional children with the same characteristics. When obese children with and without IR were compared, 47 metabolites out of 818 compounds (P<0.05) obtained after data pre-processing were found to be significantly different. Bile acids exhibit the greatest changes (that is, approximately a 90% increase in IR). The majority of metabolites differing between groups were lysophospholipids (15) and amino acids (17), indicating inflammation and central carbon metabolism as the most altered processes in impaired insulin signaling. Multivariate analysis (OPLS-DA models) showed subtle differences between groups that were magnified when females were analyzed alone. Inflammation and central carbon metabolism, together with the contribution of the gut microbiota, are the most altered processes in obese children with impaired insulin signaling in a sex-specific fashion despite their prepubertal status.

  19. Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges.

    PubMed

    Jeanes, Yvonne M; Reeves, Sue

    2017-06-01

    Women with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed with dietary interventions.

  20. Pregnancy Complicated by Obesity Induces Global Transcript Expression Alterations in Visceral and Subcutaneous Fat

    PubMed Central

    Bashiri, Asher; Heo, Hye J.; Ben-Avraham, Danny; Mazor, Moshe; Budagov, Temuri; Einstein, Francine H.; Atzmon, Gil

    2014-01-01

    Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet little is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n=4/group) at time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations lead to identification of indolethylamine N-methyltransferase (INMT), tissue factor pathway inhibitor-2 (TFPI-2), and ephrin type-B receptor 6 (EPHB6), not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity. PMID:24696292

  1. Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance.

    PubMed

    Ortiz Segura, Maria Del Carmen; Del Río Navarro, Blanca Estela; Rodríguez Espino, Benjamín Antonio; Marchat, Laurence A; Sánchez Muñoz, Fausto; Villafaña, Santiago; Hong, Enrique; Meza-Cuenca, Fabián; Mailloux Salinas, Patrick; Bolaños-Jiménez, Francisco; Zambrano, Elena; Arredondo-López, Abel Armando; Bravo, Guadalupe; Huang, Fengyang

    2017-08-01

    The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS). Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65). The circulating concentrations of leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and IR were determined by standard methods. The obese adolescents with IR presented increased presence of MetS and higher circulating concentrations in sICAM-1 in comparison with the obese subjects without IR. The lowest concentrations of adiponectin were observed in the obese with IR. In multivariate linear regression models, sICAM-1 along with triglycerides, total cholesterol, and waist circumference was strongly associated with HOMA-IR (R 2 =0.457, P=0.008). Similarly, after adjustment for age, BMI-SDS, lipids, and adipokines, HOMA-IR remained associated with sICAM-1 (R 2 =0.372, P=0.008). BMI-SDS was mildly associated with leptin (R 2 =0.176, P=0.002) and the waist circumference was mild and independent determinant of adiponectin (R 2 =0.136, P=0.007). Our findings demonstrated that the obese adolescents, particularly the obese subjects with IR exhibited increased presence of MetS, abnormality of adipokines, and endothelial dysfunction. The significant interaction between IR and endothelial dysfunction may suggest a novel therapeutic approach to prevent or delay systemic IR and the genesis of cardiovascular diseases in obese patients.

  2. Outcomes after elective abdominal aortic aneurysm repair in obese versus nonobese patients.

    PubMed

    Locham, Satinderjit; Rizwan, Muhammad; Dakour-Aridi, Hanaa; Faateh, Muhammad; Nejim, Besma; Malas, Mahmoud

    2018-06-07

    Obesity is a worldwide epidemic, particularly in Western society. It predisposes surgical patients to an increased risk of adverse outcomes. The aim of our study was to use a nationally representative vascular database and to compare in-hospital outcomes in obese vs nonobese patients undergoing elective open aortic repair (OAR) and endovascular aneurysm repair (EVAR). All patients undergoing elective abdominal aortic aneurysm repair were identified in the Vascular Quality Initiative database (2003-2017). Obesity was defined as body mass index ≥30 kg/m 2 . Univariable (Student t-test and χ 2  test) and multivariable (logistic regression) analyses were implemented to compare in-hospital mortality and any major complications (wound infection, renal failure, and cardiopulmonary failure) in obese vs nonobese patients. We identified a total of 33,082 patients undergoing elective OAR (nonobese, n = 4605 [72.4%]; obese, n = 1754 [27.6%]) and EVAR (nonobese, n = 18,338 [68.6%]; obese, n = 8385 [31.4%]). Obese patients undergoing OAR and EVAR were relatively younger compared with nonobese patients (mean age [standard deviation], 67.55 [8.26] years vs 70.27 [8.30] years and 71.06 [8.22] years vs 74.55 [8.55] years), respectively; (both P < .001). Regardless of approach, obese patients had slightly longer operative time (OAR, 259.02 [109.97] minutes vs 239.37 [99.78] minutes; EVAR, 138.27 [70.64] minutes vs 134.34 [69.98] minutes) and higher blood loss (OAR, 2030 [1823] mL vs 1619 [1642] mL; EVAR, 228 [354] mL vs 207 [312] mL; both P < .001). There was no significant difference in mortality between the two groups undergoing OAR and EVAR (OAR, 2.9% vs 3.2% [P = .50]; EVAR, 0.5% vs 0.6% [P = .76]). On multivariable analysis, obese patients undergoing OAR had 33% higher odds of renal failure (adjusted odds ratio [OR], 1.33; 95% confidence interval [CI], 1.09-1.63; P = .006) and 75% higher odds of wound infections (adjusted OR, 1.75; 95% CI, 1.11-2.76; P = .02

  3. Higher association of coronary artery calcification with non-alcoholic fatty liver disease than with abdominal obesity in middle-aged Korean men: the Kangbuk Samsung Health Study.

    PubMed

    Lee, Min-Kyung; Park, Hye-Jeong; Jeon, Won Seon; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

    2015-07-15

    It is uncertain whether non-alcoholic fatty liver disease (NAFLD) or abdominal obesity is more associated with atherosclerosis. The aim of this study was to determine whether NAFLD or abdominal obesity is more strongly associated with subclinical atherosclerosis represented by coronary artery calcification (CAC). A total of 21,335 male participants in a health screening program (mean age 41 years) were enrolled. Ultrasonographic measurements of fatty liver and multi-detector computed tomography were performed to determine the coronary artery calcium score (CACS). The presence of CAC was defined as CACS > 0. Subjects were divided into four groups according to the presence or absence of NAFLD and/or abdominal obesity as assessed by waist-hip ratio (WHR) > 0.9. The presence of CAC was detected in 2,385 subjects (11.2%). The proportion of subjects with CAC was highest in the abdominal obesity only group (23.2%). After adjustment for age, diabetes history, hypertension, cigarette smoking, and physical inactivity, the odds ratio (OR) for CAC was the highest in the group with both abnormalities [1.465 (1.324-1.623)]. The NAFLD only group showed significantly increased OR for CAC compared to that in the abdominal obesity only group [1.286 (1.151-1.436) vs. 1.076 (0.939-1.233)]. Non-alcoholic fatty liver disease is more closely associated with CAC than abdominal obesity as assessed by the WHR. NAFLD could be considered an independent determinant of subclinical atherosclerosis as assessed by CAC.

  4. Evaluation of Mn-superoxide dismutase and catalase gene expression in childhood obesity: its association with insulin resistance.

    PubMed

    Mohseni, Roohollah; Arab Sadeghabadi, Zahra; Goodarzi, Mohammad Taghi; Teimouri, Maryam; Nourbakhsh, Mitra; Razzaghy Azar, Maryam

    2018-06-28

    Obesity is associated with oxidative stress. Superoxide dismutase (SOD) is the first line of defense against reactive oxygen species (ROS), eliminating the strong superoxide radical and producing H2O2, which can then be degraded by catalase (CAT). The main objective of this study was to evaluate the gene expression antioxidant enzymes (Mn-SOD and CAT) in peripheral blood mononuclear cells (PBMCs) of obese and normal-weight children, and its association with anthropometric and biochemical parameters. Thirty obese and 30 control subjects between the ages of 8 and 16 years were enrolled in this study. Serum insulin levels were measured using enzyme-linked immunosorbent assay (ELISA), and insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Biochemical parameters were also measured. PBMCs of the subjects were separated and Mn-SOD and CAT gene expression was measured using real-time polymerase chain reaction (PCR). Mn-SOD and CAT gene expression was significantly lower in the obese group compared with the control group (p<0.01). Also, a positive correlation was observed between the gene expression of Mn-SOD and CAT and body mass index (BMI), fasting blood sugar, insulin resistance, low density lipoprotein-cholesterol (LDL-C) cholesterol, triglycerides (TG) and systolic blood pressure (SBP). Induction of antioxidants, especially Mn-SOD and CAT, can lead to reduction of oxidative stress and prevent the complications of obesity in children.

  5. Double-stranded RNA-activated protein kinase is a key modulator of insulin sensitivity in physiological conditions and in obesity in mice.

    PubMed

    Carvalho-Filho, M A; Carvalho, B M; Oliveira, A G; Guadagnini, D; Ueno, M; Dias, M M; Tsukumo, D M; Hirabara, S M; Reis, L F; Curi, R; Carvalheira, J B C; Saad, Mario J A

    2012-11-01

    The molecular integration of nutrient- and pathogen-sensing pathways has become of great interest in understanding the mechanisms of insulin resistance in obesity. The double-stranded RNA-dependent protein kinase (PKR) is one candidate molecule that may provide cross talk between inflammatory and metabolic signaling. The present study was performed to determine, first, the role of PKR in modulating insulin action and glucose metabolism in physiological situations, and second, the role of PKR in insulin resistance in obese mice. We used Pkr(-/-) and Pkr(+/+) mice to investigate the role of PKR in modulating insulin sensitivity, glucose metabolism, and insulin signaling in liver, muscle, and adipose tissue in response to a high-fat diet. Our data show that in lean Pkr(-/-) mice, there is an improvement in insulin sensitivity, and in glucose tolerance, and a reduction in fasting blood glucose, probably related to a decrease in protein phosphatase 2A activity and a parallel increase in insulin-induced thymoma viral oncogene-1 (Akt) phosphorylation. PKR is activated in tissues of obese mice and can induce insulin resistance by directly binding to and inducing insulin receptor substrate (IRS)-1 serine307 phosphorylation or indirectly through modulation of c-Jun N-terminal kinase and inhibitor of κB kinase β. Pkr(-/-) mice were protected from high-fat diet-induced insulin resistance and glucose intolerance and showed improved insulin signaling associated with a reduction in c-Jun N-terminal kinase and inhibitor of κB kinase β phosphorylation in insulin-sensitive tissues. PKR may have a role in insulin sensitivity under normal physiological conditions, probably by modulating protein phosphatase 2A activity and serine-threonine kinase phosphorylation, and certainly, this kinase may represent a central mechanism for the integration of pathogen response and innate immunity with insulin action and metabolic pathways that are critical in obesity.

  6. Changes in visceral adiposity and serum cholesterol with a novel viscous polysaccharide in Japanese adults with abdominal obesity.

    PubMed

    Reimer, Raylene A; Yamaguchi, Hideyo; Eller, Lindsay K; Lyon, Michael R; Gahler, Roland J; Kacinik, Veronica; Juneja, Prateek; Wood, Simon

    2013-09-01

    Evidence supports the role of dietary fiber in improving metabolic health. PolyGlycopleX (PGX), a viscous functional polysaccharide improves lipidemia and glycemia in healthy adults. Our objective was to examine the effects of PGX on risk factors associated with the metabolic syndrome in Japanese adults with abdominal obesity. Sixty four subjects assigned to 14 weeks of 15 g day(-1) of PGX or placebo were assessed in a randomized, double-blind, placebo-controlled, parallel group trial. At week 0 and 14, primary outcome measures were serum lipids, abdominal adiposity, glucose tolerance and blood pressure. Total and LDL cholesterol were reduced at week 14 with PGX but not placebo (P < 0.05). The reduction in waist circumference at week 14 was greater with PGX versus placebo (P < 0.05). In females, abdominal visceral fat was decreased to a greater extent with PGX versus placebo (P < 0.05). While glucose tolerance worsened with placebo over time, PGX reduced glucose total area under the curve from week 0 to 6 (P = 0.039). Serum concentrations of resistin and IL6 increased slightly in placebo and decreased slightly with PGX . PGX is a functional fiber that shows promise in reducing risk factors related to the metabolic syndrome in Japanese adults with abdominal obesity. Copyright © 2013 The Obesity Society.

  7. Insulin Sensitivity and Secretion in Obese Type 2 Diabetic Women after Various Bariatric Operations

    PubMed Central

    Vrbikova, Jana; Kunesova, Marie; Kyrou, Ioannis; Tura, Andrea; Hill, Martin; Grimmichova, Tereza; Dvorakova, Katerina; Sramkova, Petra; Dolezalova, Karin; Lischkova, Olga; Vcelak, Josef; Hainer, Vojtech; Bendlova, Bela; Kumar, Sudhesh; Fried, Martin

    2017-01-01

    Objective To compare the effects of biliopancreatic diversion (BPD) and laparoscopic gastric banding (LAGB) on insulin sensitivity and secretion with the effects of laparoscopic gastric plication (P). Methods A total of 52 obese women (age 30-66 years) suffering from type 2 diabetes mellitus (T2DM) were prospectively recruited into three study groups: 16 BPD; 16 LAGB, and 20 P. Euglycemic clamps and mixed meal tolerance tests were performed before, at 1 month and at 6 months after bariatric surgery. Beta cell function derived from the meal test parameters was evaluated using mathematical modeling. Results Glucose disposal per kilogram of fat free mass (a marker of peripheral insulin sensitivity) increased significantly in all groups, especially after 1 month. Basal insulin secretion decreased significantly after all three types of operations, with the most marked decrease after BPD compared with P and LAGB. Total insulin secretion decreased significantly only following the BPD. Beta cell glucose sensitivity did not change significantly post-surgery in any of the study groups. Conclusion We documented similar improvement in insulin sensitivity in obese T2DM women after all three study operations during the 6-month postoperative follow-up. Notably, only BPD led to decreased demand on beta cells (decreased integrated insulin secretion), but without increasing the beta cell glucose sensitivity. PMID:27951535

  8. Fatty liver disease in severe obese patients: Diagnostic value of abdominal ultrasound

    PubMed Central

    de Moura Almeida, Alessandro; Cotrim, Helma Pinchemel; Barbosa, Daniel Batista Valente; de Athayde, Luciana Gordilho Matteoni; Santos, Adimeia Souza; Bitencourt, Almir Galvão Vieira; de Freitas, Luiz Antonio Rodrigues; Rios, Adriano; Alves, Erivaldo

    2008-01-01

    AIM: To evaluate the sensitivity and specificity of abdominal ultrasound (US) for the diagnosis of hepatic steatosis in severe obese subjects and its relation to histological grade of steatosis. METHODS: A consecutive series of obese patients, who underwent bariatric surgery from October 2004 to May 2005, was selected. Ultrasonography was performed in all patients as part of routine preoperative time and an intraoperative wedge biopsy was obtained at the beginning of the bariatric surgery. The US and histological findings of steatosis were compared, considering histology as the gold standard. RESULTS: The study included 105 patients. The mean age was 37.2 ± 10.6 years and 75.2% were female. The histological prevalence of steatosis was 89.5%. The sensitivity and specificity of US in the diagnosis of hepatic steatosis were, respectively, 64.9% (95% CI: 54.9-74.3) and 90.9% (95% CI: 57.1-99.5). The positive predictive value and negative predictive value were, respectively, 98.4% (95% CI: 90.2-99.9) and 23.3% (95% CI: 12.3-39.0). The presence of steatosis on US was associated to advanced grades of steatosis on histology (P = 0.016). CONCLUSION: Preoperative abdominal US in our series has not shown to be an accurate method for the diagnosis of hepatic steatosis in severe obese patients. Until another non-invasive method demonstrates better sensitivity and specificity values, histological evaluation may be recommended to these patients undergoing bariatric surgery. PMID:18322958

  9. Endoplasmic reticulum chaperone GRP78 regulates macrophage function and insulin resistance in diet-induced obesity.

    PubMed

    Kim, Jong Hun; Lee, Eunjung; Friedline, Randall H; Suk, Sujin; Jung, Dae Young; Dagdeviren, Sezin; Hu, Xiaodi; Inashima, Kunikazu; Noh, Hye Lim; Kwon, Jung Yeon; Nambu, Aya; Huh, Jun R; Han, Myoung Sook; Davis, Roger J; Lee, Amy S; Lee, Ki Won; Kim, Jason K

    2018-04-01

    Obesity-mediated inflammation is a major cause of insulin resistance, and macrophages play an important role in this process. The 78-kDa glucose-regulated protein (GRP78) is a major endoplasmic reticulum chaperone that modulates unfolded protein response (UPR), and mice with GRP78 heterozygosity were resistant to diet-induced obesity. Here, we show that mice with macrophage-selective ablation of GRP78 (Lyz- GRP78 -/- ) are protected from skeletal muscle insulin resistance without changes in obesity compared with wild-type mice after 9 wk of high-fat diet. GRP78-deficient macrophages demonstrated adapted UPR with up-regulation of activating transcription factor (ATF)-4 and M2-polarization markers. Diet-induced adipose tissue inflammation was reduced, and bone marrow-derived macrophages from Lyz- GRP78 -/- mice demonstrated a selective increase in IL-6 expression. Serum IL-13 levels were elevated by >4-fold in Lyz- GRP78 -/- mice, and IL-6 stimulated the myocyte expression of IL-13 and IL-13 receptor. Lastly, recombinant IL-13 acutely increased glucose metabolism in Lyz- GRP78 -/- mice. Taken together, our data indicate that GRP78 deficiency activates UPR by increasing ATF-4, and promotes M2-polarization of macrophages with a selective increase in IL-6 secretion. Macrophage-derived IL-6 stimulates the myocyte expression of IL-13 and regulates muscle glucose metabolism in a paracrine manner. Thus, our findings identify a novel crosstalk between macrophages and skeletal muscle in the modulation of obesity-mediated insulin resistance.-Kim, J. H., Lee, E., Friedline, R. H., Suk, S., Jung, D. Y., Dagdeviren, S., Hu, X., Inashima, K., Noh, H. L., Kwon, J. Y., Nambu, A., Huh, J. R., Han, M. S., Davis, R. J., Lee, A. S., Lee, K. W., Kim, J. K. Endoplasmic reticulum chaperone GRP78 regulates macrophage function and insulin resistance in diet-induced obesity.

  10. Indices of insulin secretion during a liquid mixed-meal test in obese youth with diabetes

    USDA-ARS?s Scientific Manuscript database

    To compare indices of insulin secretion, insulin sensitivity (IS),and oral disposition index (oDI) during the liquid mixed-meal test in obese youth with clinically diagnosed type 2 diabetes mellitus (T2DM) and negative autoantibodies (Ab-) versus those with T2DM and positive autoantibodies (Ab+) to ...

  11. Adipocyte-specific deficiency of NADPH oxidase 4 delays the onset of insulin resistance and attenuates adipose tissue inflammation in obesity

    PubMed Central

    Den Hartigh, Laura J.; Omer, Mohamed; Goodspeed, Leela; Wang, Shari; Wietecha, Tomasz; O’Brien, Kevin D.; Han, Chang Yeop

    2017-01-01

    Objective Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown. Approach and Results In this study, control C57BL/6 mice and mice in which NOX4 has been deleted specifically in adipocytes were fed a high fat, high sucrose (HFHS) diet. During the development of obesity in control mice, adipocyte NOX4 and PPP activity were transiently increased. Primary adipocytes differentiated form mice with adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged HFHS feeding. Conclusions These findings imply that NOX4-derived ROS may play a role in the onset of insulin resistance and adipose tissue inflammation. As such, therapeutics targeting NOX4-mediated ROS production could be effective in preventing obesity-associated conditions such as insulin resistance. PMID:28062496

  12. Adipocyte-Specific Deficiency of NADPH Oxidase 4 Delays the Onset of Insulin Resistance and Attenuates Adipose Tissue Inflammation in Obesity.

    PubMed

    Den Hartigh, Laura J; Omer, Mohamed; Goodspeed, Leela; Wang, Shari; Wietecha, Tomasz; O'Brien, Kevin D; Han, Chang Yeop

    2017-03-01

    Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown. In this study, control C57BL/6 mice and mice in which NOX4 has been deleted specifically in adipocytes were fed a high-fat, high-sucrose diet. During the development of obesity in control mice, adipocyte NOX4 and pentose phosphate pathway activity were transiently increased. Primary adipocytes differentiated from mice with adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged high-fat, high-sucrose feeding. These findings imply that NOX4-derived ROS may play a role in the onset of insulin resistance and adipose tissue inflammation. As such, therapeutics targeting NOX4-mediated ROS production could be effective in preventing obesity-associated conditions, such as insulin resistance. © 2016 American Heart Association, Inc.

  13. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance.

    PubMed

    Lee, Byung-Cheol; Lee, Jongsoon

    2014-03-01

    There is increasing evidence showing that inflammation is an important pathogenic mediator of the development of obesity-induced insulin resistance. It is now generally accepted that tissue-resident immune cells play a major role in the regulation of this obesity-induced inflammation. The roles that adipose tissue (AT)-resident immune cells play have been particularly extensively studied. AT contains most types of immune cells and obesity increases their numbers and activation levels, particularly in AT macrophages (ATMs). Other pro-inflammatory cells found in AT include neutrophils, Th1 CD4 T cells, CD8 T cells, B cells, DCs, and mast cells. However, AT also contains anti-inflammatory cells that counter the pro-inflammatory immune cells that are responsible for the obesity-induced inflammation in this tissue. These anti-inflammatory cells include regulatory CD4 T cells (Tregs), Th2 CD4 T cells, and eosinophils. Hence, AT inflammation is shaped by the regulation of pro- and anti-inflammatory immune cell homeostasis, and obesity skews this balance towards a more pro-inflammatory status. Recent genetic studies revealed several molecules that participate in the development of obesity-induced inflammation and insulin resistance. In this review, the cellular and molecular players that participate in the regulation of obesity-induced inflammation and insulin resistance are discussed, with particular attention being placed on the roles of the cellular players in these pathogeneses. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. [Metabolic profile in obese patients with obstructive sleep apnea. A comparison between patients with insulin resistance and with insulin sensitivity].

    PubMed

    Dumitrache-Rujinski, Stefan; Dinu, Ioana; Călcăianu, George; Erhan, Ionela; Cocieru, Alexandru; Zaharia, Dragoş; Toma, Claudia Lucia; Bogdan, Miron Alexandru

    2014-01-01

    Obstructive sleep apnea syndrome (OSAS) may induce metabolic abnormalities through intermittent hypoxemia and simpathetic activation. It is difficult to demonstrate an independent role of OSAS in the occurrence of metabolic abnormalities, as obesity represents an important risk factor for both OSAS and metabolic abnormalities. to assess the relations between insulin resistance (IR), insulin sensitivity (IS), OSAS severity and nocturnal oxyhaemoglobin levels in obese, nondiabetic patients with daytime sleepiness. We evaluated 99 consecutive, obese, nondiabetic patients (fasting glycemia < 126 mg/dL, no hypoglycemic or hypolipemiant medication) diagnosed with OSAS (AHI > 5/hour and daytime sleepiness) by an ambulatory six channel cardio-respiratory polygraphy. Hight, weight serum triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) levels were evaluated. Correlations between Apneea Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), average and lowest oxyhaemoglobin saturation (SaO), body mass index (BMI) and insulin resistance or sensitivity were assesed. IR was defined as a TG/ HDL-Cratio > 3, and insulin sensitivity (IS) as a TG/HDL-C ratio < 2. 64 patients (out of 99) had lR and 18 IS. In the IR group (44 men and 20 women), the mean age was 52 +/- 10.6 years, mean BMI: 38.54 +/- 6.67 Kg/m2 (30-60), TG/HDL-C:5, 27 +/- 2.03 (3.02-11.1), mean AHI: 49.65 +/- 25.55/hour (7-110), mean ODI: 4769 +/- 24.95/hour (4-98), mean average SaO2 89.42 +/- 4.6 and mean lowest SaO2 68.4% +/- 13.8% (32-88%). 48 patients had severe, 7 moderate and 9 mild OSAS. In the IS group (10 men and 8 women), the mean age was 58.4 +/- 8.2years, mean BMI: 35.4 +/- 4.29 Kg/m2 (30-46), TG/ HDL-C: 1.64 +/- 0.29 (1.13-1.95), mean AHI: 45.8 +/- 30.3/hour (9-131), mean ODI: 39.9 +/- 32.2/hour (2-133), mean average SaO2 90.8 +/- 8.2 (81-95) and mean lowest SaO2: 74% +/- 10.8% (52-87%). 12 patients had severe, 3 moderate and 3 mild OSAS. Insulin sensitivity positively correlated with mean

  15. C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance.

    PubMed

    Lei, Xia; Seldin, Marcus M; Little, Hannah C; Choy, Nicholas; Klonisch, Thomas; Wong, G William

    2017-09-08

    Obesity is associated with chronic low-grade inflammation, and metabolic regulators linking obesity to inflammation have therefore received much attention. Secreted C1q/TNF-related proteins (CTRPs) are one such group of regulators that regulate glucose and fat metabolism in peripheral tissues and modulate inflammation in adipose tissue. We have previously shown that expression of CTRP6 is up-regulated in leptin-deficient mice and, conversely, down-regulated by the anti-diabetic drug rosiglitazone. Here, we provide evidence for a novel role of CTRP6 in modulating both inflammation and insulin sensitivity. We found that in obese and diabetic humans and mouse models, CTRP6 expression was markedly up-regulated in adipose tissue and that stromal vascular cells, such as macrophages, are a major CTRP6 source. Overexpressing mouse or human CTRP6 impaired glucose disposal in peripheral tissues in response to glucose and insulin challenge in wild-type mice. Conversely, Ctrp6 gene deletion improved insulin action and increased metabolic rate and energy expenditure in diet-induced obese mice. Mechanistically, CTRP6 regulates local inflammation and glucose metabolism by targeting macrophages and adipocytes, respectively. In cultured macrophages, recombinant CTRP6 dose-dependently up-regulated the expression and production of TNF-α. Conversely, CTRP6 deficiency reduced circulating inflammatory cytokines and pro-inflammatory macrophages in adipose tissue. CTRP6-overexpressing mice or CTRP6-treated adipocytes had reduced insulin-stimulated Akt phosphorylation and glucose uptake. In contrast, loss of CTRP6 enhanced insulin-stimulated Akt activation in adipose tissue. Together, these results establish CTRP6 as a novel metabolic/immune regulator linking obesity to adipose tissue inflammation and insulin resistance. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

    PubMed

    McCormack, S E; Shaham, O; McCarthy, M A; Deik, A A; Wang, T J; Gerszten, R E; Clish, C B; Mootha, V K; Grinspoon, S K; Fleischman, A

    2013-02-01

    What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index. Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance. Sixty-nine healthy subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a prospective longitudinal cohort for 18 months (n = 17 with complete data). Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P = 0.046). Elevations in the concentrations of circulating BCAAs are significantly

  17. Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune Adipose Inflammation or Insulin Resistance in Obesity.

    PubMed

    Subramanian, Manikandan; Ozcan, Lale; Ghorpade, Devram Sampat; Ferrante, Anthony W; Tabas, Ira

    2015-01-01

    Obesity-induced inflammation in visceral adipose tissue (VAT) is a major contributor to insulin resistance and type 2 diabetes. Whereas innate immune cells, notably macrophages, contribute to visceral adipose tissue (VAT) inflammation and insulin resistance, the role of adaptive immunity is less well defined. To address this critical gap, we used a model in which endogenous activation of T cells was suppressed in obese mice by blocking MyD88-mediated maturation of CD11c+ antigen-presenting cells. VAT CD11c+ cells from Cd11cCre+Myd88fl/fl vs. control Myd88fl/fl mice were defective in activating T cells in vitro, and VAT T and B cell activation was markedly reduced in Cd11cCre+Myd88fl/fl obese mice. However, neither macrophage-mediated VAT inflammation nor systemic inflammation were altered in Cd11cCre+Myd88fl/fl mice, thereby enabling a focused analysis on adaptive immunity. Unexpectedly, fasting blood glucose, plasma insulin, and the glucose response to glucose and insulin were completely unaltered in Cd11cCre+Myd88fl/fl vs. control obese mice. Thus, CD11c+ cells activate VAT T and B cells in obese mice, but suppression of this process does not have a discernible effect on macrophage-mediated VAT inflammation or systemic glucose homeostasis.

  18. Blunted Suppression of Acyl-Ghrelin in Response to Fructose Ingestion in Obese Adolescents: the Role of Insulin Resistance

    PubMed Central

    Van Name, Michelle; Giannini, Cosimo; Santoro, Nicola; Jastreboff, Ania; Kubat, Jessica; Li, Fangyong; Kursawe, Romy; Savoye, Mary; Duran, Elvira; Dziura, James; Sinha, Rajita; Sherwin, Robert; Cline, Gary; Caprio, Sonia

    2015-01-01

    Objective Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared to glucose ingestion. We evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity. Methods Adolescents were divided into lean (n=14), obese insulin sensitive (n=12) (OIS), and obese insulin resistant (n=15) (OIR). In a double-blind, cross-over design, subjects drank 75g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes. Results Baseline acyl-ghrelin was highest in lean and lowest in OIR (p=0.02). After glucose ingestion acyl-ghrelin decreased similarly in lean and OIS, but appeared lower in OIR (vs lean p=0.03). Suppression differences were more pronounced after fructose (lean vs. OIS p=0.008, lean vs. OIR p<0.001). OIS became significantly hungrier after fructose (p=0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose. Conclusion Compared to lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating. PMID:25645909

  19. Overweight, obesity and features of metabolic syndrome in children with diabetes treated with insulin pump therapy.

    PubMed

    Łuczyński, Włodzimierz; Szypowska, Agnieszka; Głowińska-Olszewska, Barbara; Bossowski, Artur

    2011-07-01

    There has been no specific evaluation of atherogenic risk factors in children with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). We, therefore, studied the prevalence of overweight/obesity and metabolic syndrome among these patients. Five hundred children with T1DM treated with CSII and multiple daily insulin (MDI) regimen were included in the study. Anthropometric data/physical examination, data concerning diabetes, and a lipid profile were assessed in this group, and compared with respect to treatment method (CSII vs. MDI). Almost one-third (30.2%) of the children were overweight/obese. The body mass index (BMI) values at the time of the present evaluation were significantly higher in comparison with the BMI values 3-6 months after the diagnosis. Dyslipidemia was recognized in 51.6%, hypertension in 4.8%, and the metabolic syndrome in 3.2%. of the subjects. The overweight/obese children differed from their normal-weight counterparts with respect to metabolic control, the incidence of hypertension, dyslipidemia, and metabolic syndrome. The girls showed higher prevalence of overweight/obesity and higher BMI values compared to the boys. The children treated with CSII had the same prevalence of overweight/obesity, but a lower incidence of dyslipidemia, and a better metabolic control compared to the children treated with MDI regimen. Our study shows a high prevalence of overweight/obesity and dyslipidemia in children with T1DM including those treated with an insulin pump.

  20. Changes in abdominal obesity in Chilean university students stratified by body mass index.

    PubMed

    Cossio-Bolaños, Marco; Vilchez-Avaca, Catalina; Contreras-Mellado, Victor; Andruske, Cynthia Lee; Gómez-Campos, Rossana

    2016-01-13

    Studies based on Body Mass Index (BMI) and waist circumference (WC) are generally used to examine the prevalence and tendency of overweight and obesity. These studies help determine the socioeconomic development of a country and improve public health policies. Therefore, the goal of this research was to determine the trend of change in abdominal obesity of Chilean university students according to the Body Mass Index (BMI) measured in intervals of three and six years. For this study, a total of 1598 students of both sexes ranging in age from 18 to 26 from a Chilean university were evaluated. Students were assessed commencing in 2007 (372 males and 315 females), 2010 (250 males and 330 females), and ending in 2013 (153 males and 178 females). During the three transversal assessments, weight, height, and waist circumference were evaluated. BMI was calculated for both sexes. No significant differences were found in age and BMI during the three years evaluated (2007, 2010, and 2013). In 2013, waist circumference (WC) increased significantly (p < 0.001 for both sexes). Moreover, in 2013, in all the percentiles evaluated, high values of WC were compared in relation to previous years. Furthermore, in 2013, in all four BMI categories (underweight, normal, overweight, and obese), the university students showed significant increases in WC (Females: p = 0.004; Males: p = 0.035) whereas in 2007 and 2010, the values remained relatively stable. BMI remained constant during 2007, 2010, and 2013. However, the university students of both sexes showed greater risk of abdominal obesity as a result of increased WC in 2013.

  1. Relationships of Dietary Histidine and Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study.

    PubMed

    Li, Yan-Chuan; Li, Chun-Long; Qi, Jia-Yue; Huang, Li-Na; Shi, Dan; Du, Shan-Shan; Liu, Li-Yan; Feng, Ren-Nan; Sun, Chang-Hao

    2016-07-11

    Our previous studies have demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women and high-fat diet-induced obese rats. However, the effects of dietary histidine on general population are not known. The objective of this Internet-based cross-sectional study was to evaluate the associations between dietary histidine and prevalence of overweight/obesity and abdominal obesity in northern Chinese population. A total of 2376 participants were randomly recruited and asked to finish our Internet-based dietary questionnaire for the Chinese (IDQC). Afterwards, 88 overweight/obese participants were randomly selected to explore the possible mechanism. Compared with healthy controls, dietary histidine was significantly lower in overweight (p < 0.05) and obese (p < 0.01) participants of both sexes. Dietary histidine was inversely associated with body mass index (BMI), waist circumference (WC) and blood pressure in overall population and stronger associations were observed in women and overweight/obese participants. Higher dietary histidine was associated with lower prevalence of overweight/obesity and abdominal obesity, especially in women. Further studies indicated that higher dietary histidine was associated with lower fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), 2-h postprandial glucose (2 h-PG), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (CRP), malonaldehyde (MDA) and vaspin and higher glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and adiponectin of overweight/obese individuals of both sexes. In conclusion, higher dietary histidine is inversely associated with energy intake, status of insulin resistance, inflammation and oxidative stress in overweight/obese participants and lower prevalence of overweight/obesity in northern Chinese adults.

  2. Relationships of Dietary Histidine and Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study

    PubMed Central

    Li, Yan-Chuan; Li, Chun-Long; Qi, Jia-Yue; Huang, Li-Na; Shi, Dan; Du, Shan-Shan; Liu, Li-Yan; Feng, Ren-Nan; Sun, Chang-Hao

    2016-01-01

    Our previous studies have demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women and high-fat diet-induced obese rats. However, the effects of dietary histidine on general population are not known. The objective of this Internet-based cross-sectional study was to evaluate the associations between dietary histidine and prevalence of overweight/obesity and abdominal obesity in northern Chinese population. A total of 2376 participants were randomly recruited and asked to finish our Internet-based dietary questionnaire for the Chinese (IDQC). Afterwards, 88 overweight/obese participants were randomly selected to explore the possible mechanism. Compared with healthy controls, dietary histidine was significantly lower in overweight (p < 0.05) and obese (p < 0.01) participants of both sexes. Dietary histidine was inversely associated with body mass index (BMI), waist circumference (WC) and blood pressure in overall population and stronger associations were observed in women and overweight/obese participants. Higher dietary histidine was associated with lower prevalence of overweight/obesity and abdominal obesity, especially in women. Further studies indicated that higher dietary histidine was associated with lower fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), 2-h postprandial glucose (2 h-PG), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (CRP), malonaldehyde (MDA) and vaspin and higher glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and adiponectin of overweight/obese individuals of both sexes. In conclusion, higher dietary histidine is inversely associated with energy intake, status of insulin resistance, inflammation and oxidative stress in overweight/obese participants and lower prevalence of overweight/obesity in northern Chinese adults. PMID:27409634

  3. Increased chemerin concentrations in fetuses of obese mothers and correlation with maternal insulin sensitivity.

    PubMed

    Barker, Gillian; Lim, Ratana; Rice, Gregory E; Lappas, Martha

    2012-11-01

    The aim of this study was to determine the effect of maternal obesity and gestational diabetes mellitus (GDM) on (i) the circulating concentrations of chemerin in cord and maternal plasma, and (ii) gene expression and release of chemerin from human placenta and adipose tissue. Chemerin concentrations were measured in maternal and cord plasma from 62 normal glucose tolerant women (NGT) and 69 women with GDM at the time of term elective Caesarean section. Placenta and adipose tissue expression and release of chemerin was measured from 22 NGT and 22 GDM women. There was no effect of maternal obesity or GDM on maternal chemerin concentrations. Chemerin concentrations were significantly higher in cord plasma from women with maternal obesity. Cord chemerin concentrations in NGT women negatively correlated with the concentrations of maternal insulin sensitivity. There was no effect of GDM on maternal and cord chemerin concentrations, and on the release of chemerin from placenta and adipose tissue. At the time of term Caesarean section, preexisting maternal obesity, and its associated insulin resistance, is associated with higher cord plasma chemerin concentrations.

  4. Gender differences in the prevalence and development of metabolic syndrome in Chinese population with abdominal obesity.

    PubMed

    Xu, Shaoyong; Gao, Bin; Xing, Ying; Ming, Jie; Bao, Junxiang; Zhang, Qiang; Wan, Yi; Ji, Qiuhe

    2013-01-01

    Not all the people with metabolic syndrome (MS) have abdominal obesity (AO). The study aimed to investigate gender differences in the prevalence and development of MS in Chinese population with abdominal obesity, which has rarely been reported. Data were obtained from the 2007-08 China National Diabetes and Metabolic Disorders Study, and participants were divided into two samples for analysis. Sample 1 consisted of 19,046 people with abdominal obesity, while sample 2 included 2,124 people meeting pre-specified requirements. Survival analysis was used to analyze the development of MS. The age-standardized prevalence of MS in Chinese population with AO was 49.5%. The prevalence in males (73.7%) was significantly higher than that in females (36.9%). Males had significantly higher proportions of combinations of three or four MS components than females (36.4% vs. 30.2% and 18.4% vs. 5%, respectively). MS developed quick at first and became slow down later. Half of the participants with AO developed to MS after 3.9 years (95% CI: 3.7-4.1) from the initial metabolic abnormal component, whereas 75% developed to MS after 7.7 years (95% CI: 7.5-7.9). Compared with females, Chinese males with AO should receive more attention because of their higher prevalence of MS and its components, more complex and risky combinations of abnormal components, and faster development of MS.

  5. Serum Chemerin Levels Are Associated with Abdominal Visceral Fat in Type 2 Diabetes.

    PubMed

    Han, Juyoung; Kim, So Hun; Suh, Young Ju; Lim, Hyun Ae; Shin, Heekyoung; Cho, Soon Gu; Kim, Chei Won; Lee, Seung Youn; Lee, Dae Hyung; Hong, Seongbin; Kim, Yong Seong; Nam, Moon-Suk

    2016-06-01

    Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.

  6. Overall and abdominal obesity and incident aortic valve stenosis: two prospective cohort studies

    PubMed Central

    Larsson, Susanna C.; Wolk, Alicja; Håkansson, Niclas; Bäck, Magnus

    2017-01-01

    Abstract Aims The aim of this study was to examine the association of overall and abdominal obesity with aortic valve stenosis (AVS) incidence in two prospective cohorts. Methods and results We used data from the Cohort of Swedish Men and the Swedish Mammography Cohort, involving 71 817 men and women who were free of cardiovascular disease and had reported their anthropometric measures in 1997. Aortic valve stenosis cases were ascertained through linkage with nationwide registers on hospitalization and causes of death. Data were analysed using Cox proportional hazards regression. During a mean follow-up of 15.3 years, 1297 incident AVS cases (771 in men; 526 in women) were ascertained. Both overall and abdominal obesity, measured as body mass index (BMI) and waist circumference, respectively, was associated with AVS incidence, with similar associations in men and women. Compared with BMI 18.5–22.5 kg/m2, the multivariable hazard ratios were 1.24 (95% confidence interval [CI] 1.05–1.48) for overweight (BMI 25.0–29.9 kg/m2) and 1.81 (95% CI 1.47–2.23) for obesity (BMI ≥30 kg/m2). The hazard ratio for substantially increased waist circumference (men: ≥102 cm; women: ≥88 cm) compared with normal waist circumference (men: <94 cm; women: <80 cm) was 1.30 (95% CI 1.12–1.51). The proportion of AVS cases estimated to be attributed to overweight and obesity combined (BMI ≥25 kg/m2) was 10.8% (95% CI 5.2–16.4%). Conclusion These findings indicate that obesity is associated with an increased risk of AVS and that a large proportion of the cases may be prevented if the population maintained a healthy BMI. PMID:28402538

  7. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kanno, Ayumi, E-mail: akanno@med.kobe-u.ac.jp; Asahara, Shun-ichiro, E-mail: asahara@med.kobe-u.ac.jp; Masuda, Katsuhisa, E-mail: katsuhisa.m.0707@gmail.com

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage ofmore » insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets.« less

  8. [Overweight, obesity and metabolic syndrome in children with type 1 diabetes melllitus].

    PubMed

    Luczyński, Włodzimierz; Szypowska, Agnieszka; Bossowski, Artur; Ramotowska, Anna; Rećko, Przemysław; Rembińska, Małgorzata; Tercjak, Magdalena; Blecharczyk, Bernadetta; Lachowska, Urszula; Suchoń, Paweł; Wiśniewska, Karolina; Bernatowicz, Paweł; Głowińska-Olszewska, Barbara

    2010-01-01

    Obesity can be an additional risk factor for developing cardiovascular diseases in patients with diabetes. Aim of the study was the assessment of overweight, obesity and other elements of the metabolic syndrome in children with type 1 diabetes mellitus. 300 children treated with insulin at least one year were enrolled in the study. In the examined group anthropometric data, data concerned with diabetes and additional laboratory tests including risk factors for cardiovascular diseases were assessed. The median age of the examined group was 13.7 years. The body mass deficiency was noted in 0.66%, normal body mass in 71.6%, overweight in 15.3% and obesity in 12.3%. The abdominal obesity was noted in 16.0% of children. The rise in the body weight between 3-6 months from the beginning of the insulin therapy and the present assessment was statistically significant. Children with normal weight had a better metabolic control in comparison to children with overweight/obesity. Girls had a higher rise in body mass index values between the time of diagnosis and the present investigation compared to boys. Higher values of blood pressure or hypertension were noted in 16.6% of children. Altogether in 25.3% of children some dyslipidemia was observed. The metabolic syndrome criteria were noted in: 28.0% - one criterion, 13.0% - two criteria, and 0.3% - three criteria. The population of children with type 1 diabetes is characterized by high frequency of overweight/obesity, abdominal obesity, dyslipidemia and hypertension. The features of metabolic syndrome are less frequent. It is worthwhile to monitor the risk for development of cardiovascular diseases in this group of children.

  9. Assessment of insulin sensitivity from measurements in fasting state and during an oral glucose tolerance test in obese children.

    PubMed

    Atabek, Mehmet Emre; Pirgon, Ozgur

    2007-02-01

    Few previous studies have examined the validity of the fasting glucose-to-insulin ratio (FGIR), homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI) in pediatric populations. To compare simple indices of insulin resistance calculated from fasting glucose and insulin levels with insulin sensitivity indices (area under the response curve [AUCinsulin], insulin sensitivity index [ISI-compositeL) determined by oral glucose tolerance testing (OGTT) in obese children. One hundred and forty-eight obese children and adolescents (86 girls and 62 boys, mean age: 10.86 +/- 3.08 years, mean body mass index (BMI): 27.7 +/- 4.2) participated in the study. OGTT was performed in all participants. After glucose and insulin measurements from OGTT, the children were divided into two groups according to the presence or absence of insulin resistance. Insulin sensitivity indices obtained from the OGTT were compared between the groups. The total plasma glucose response and insulin secretion were evaluated from the AUC estimated by the trapezoid rule. Cut-off points, and sensitivity and specificity calculations were based on insulin resistance with receiver operating characteristic curve (ROC) analysis. The prevalence of insulin resistance, glucose intolerance and dyslipidemia was 37.1%, 24.3% and 54% in obese children, respectively. The groups consisted of 93 children without insulin resistance (54 girls and 39 boys; mean age: 10.5 +/- 3.3 years; mean BMI: 27.0 +/- 4.2) and 55 children with insulin resistance (32 girls and 23 boys; mean age: 11.4 +/- 2.5 years; mean BMI: 27.9 +/- 3.9). There were significant differences in mean FGIR (10.0 +/- 7.2 vs 5.6 +/- 2.8, p < 0.001), HOMA-IR (3.2 +/- 2.3 vs 4.9 +/- 2.3, p < 0.001) and QUICKI (0.33 +/- 0.03 vs 0.30 +/- 0.02, p < 0.001) between the groups. The cut-off points for diagnosis of insulin resistance were < 5.6 for FGIR (sensitivity 61.8, specificity 76.3), > 2.7 for HOMA

  10. Monosodium glutamate versus diet induced obesity in pregnant rats and their offspring.

    PubMed

    Afifi, M M; Abbas, Amr M

    2011-06-01

    We aim at determining the role of monosodium glutamate (MSG) compared with high caloric chow(HCC) in development of obesity in pregnant rats and their offspring. Ninety pregnant rats were divided into 3 groups, control, MSG and HCC fed. We determined energy intake, body weight (BW), abdominal fat, fat to body weight ratio, serum glucose, insulin, leptin, lipid profile, ob and leptin receptor-b gene expressions in pregnant rats and ob and leptin receptor-b gene expressions, serum insulin,glucose, leptin, triacylglycerides (TAG), total lipids (TL) and BW in offspring. Although daily energy intake and BW of MSG treated rats were lower than those of HCC fed rats, their abdominal fat and fat body weight ratio were higher. MSG or HCC increased Ob gene expression, leptin, insulin,LDL, cholesterol, total lipids (TL), glucose and decreased leptin receptor-b gene expression. In offspring of MSG treated rats, BW, serum glucose, insulin, leptin, TAG, TL and Ob gene expression increased and leptin receptor-b gene expression decreased whereas in offspring of HCC fed rats, serum insulin, leptin, Ob and leptin receptor-b gene expression increased but serum glucose, TAG, TL or BW did not change. We conclude that in pregnant rats, MSG, in spite of mild hypophagia, caused severe increase in fat body weight ratio, via leptin resistance, whereas, HCC increased BW and fat body weight ratio, due to hyperphagia with consequent leptin resistance. Moreover, maternal obesity in pregnancy, caused by MSG, has greater impact on offspring metabolism and BW than that induced by HCC.

  11. Arabian Peninsula men tend to insulin resistance and cardiovascular risk seen in South Asians.

    PubMed

    Pugh, R N; Hossain, M M; Malik, M; El Mugamer, I T; White, M A

    1998-02-01

    To test the hypothesis that peninsular Arabs and South Asians share a tendency to insulin resistance, differing from other ethnic groups living in the United Arab Emirates (UAE). A representative sample of 358 apparently healthy men aged 35-49 years drawn from a multiethnic office-based workforce in the UAE was tested. The sample included a reference group of expatriate South Asians, in whom insulin resistance has already been described as the cause of high coronary heart disease (CHD) mortality. All subjects were screened for CHD risk factors, including glucose tolerance and 2-h serum insulin determinations. There was a high prevalence of previously undiagnosed cases of diabetes (10.1%) and hypertension (14.2%). South Asian and peninsular Arab men shared the tendency to significantly higher 2-h glucose and insulin levels, lower HDL cholesterol concentrations and abdominal obesity especially compared to Europeans, who were five times less likely to be glucose-intolerant (OR 5.40, P = 0.015). Three other Arab groups were intermediate in most trends. Susceptibility to insulin resistance in Arabian peninsula men is strongly supported, suggesting that control of obesity and promotion of exercise are the best approach to CHD prevention.

  12. JNK Activation of BIM Promotes Hepatic Oxidative Stress, Steatosis, and Insulin Resistance in Obesity.

    PubMed

    Litwak, Sara A; Pang, Lokman; Galic, Sandra; Igoillo-Esteve, Mariana; Stanley, William J; Turatsinze, Jean-Valery; Loh, Kim; Thomas, Helen E; Sharma, Arpeeta; Trepo, Eric; Moreno, Christophe; Gough, Daniel J; Eizirik, Decio L; de Haan, Judy B; Gurzov, Esteban N

    2017-12-01

    The members of the BCL-2 family are crucial regulators of the mitochondrial pathway of apoptosis in normal physiology and disease. Besides their role in cell death, BCL-2 proteins have been implicated in the regulation of mitochondrial oxidative phosphorylation and cellular metabolism. It remains unclear, however, whether these proteins have a physiological role in glucose homeostasis and metabolism in vivo. In this study, we report that fat accumulation in the liver increases c-Jun N-terminal kinase-dependent BCL-2 interacting mediator of cell death (BIM) expression in hepatocytes. To determine the consequences of hepatic BIM deficiency in diet-induced obesity, we generated liver-specific BIM-knockout (BLKO) mice. BLKO mice had lower hepatic lipid content, increased insulin signaling, and improved global glucose metabolism. Consistent with these findings, lipogenic and lipid uptake genes were downregulated and lipid oxidation enhanced in obese BLKO mice. Mechanistically, BIM deficiency improved mitochondrial function and decreased oxidative stress and oxidation of protein tyrosine phosphatases, and ameliorated activation of peroxisome proliferator-activated receptor γ/sterol regulatory element-binding protein 1/CD36 in hepatocytes from high fat-fed mice. Importantly, short-term knockdown of BIM rescued obese mice from insulin resistance, evidenced by reduced fat accumulation and improved insulin sensitivity. Our data indicate that BIM is an important regulator of liver dysfunction in obesity and a novel therapeutic target for restoring hepatocyte function. © 2017 by the American Diabetes Association.

  13. Fibroblast growth factor-21 restores insulin sensitivity but induces aberrant bone microstructure in obese insulin-resistant rats.

    PubMed

    Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Krishnamra, Nateetip; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpun; Wang, Xiaojie; Liang, Guang; Li, Xiaokun; Jiang, Chao; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2017-03-01

    Fibroblast growth factor (FGF)-21 is a potent endocrine factor that improves insulin resistance and obesity-associated metabolic disorders. However, concomitant activation of peroxisome proliferator-activated receptor-γ by FGF-21 makes bone susceptible to osteopenia and fragility fracture. Since an increase in body weight often induced adaptive change in bone by making it resistant to fracture, it was unclear whether FGF-21 would still induce bone defects in overweight rats. Therefore, the present study aimed to investigate bone microstructure and its mechanical properties in high fat diet (HF)-fed rats treated with 0.1 mg/kg/day FGF-21. Eighteen male rats were divided into two groups to receive either a normal diet or HF for 12 weeks. HF rats were then divided into two subgroups to receive either vehicle or FGF-21 for 4 weeks. The results showed that HF led to obesity, dyslipidemia and insulin resistance, as indicated by hyperinsulinemia with euglycemia. In HF rats, there was an increase in tibial yield displacement (an indicator of ability to be deformed without losing toughness, as determined by 3-point bending) without changes in tibial trabecular volumetric bone mineral density (vBMD) or cortical bone parameters, e.g., cortical thickness and bone area. FGF-21 treatment strongly improved the metabolic parameters and increased insulin sensitivity in HF rats. However, FGF-21-treated HF rats showed lower yield displacement, trabecular vBMD, trabecular bone volume, trabecular thickness, and osteoblast surface compared with vehicle-treated HF rats. These findings suggest that, despite being a potent antagonist of insulin resistance and visceral fat accumulation, FGF-21 is associated with bone defects in HF rats.

  14. Modulatory role of D-chiro-inositol (DCI) on LH and insulin secretion in obese PCOS patients.

    PubMed

    Genazzani, Alessandro D; Santagni, Susanna; Rattighieri, Erika; Chierchia, Elisa; Despini, Giulia; Marini, Giulia; Prati, Alessia; Simoncini, Tommaso

    2014-06-01

    Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects fertility through oligo-ovulation, hyperandrogenism and polycystic morphology of the ovaries. Since it has been demonstrated a high incidence of insulin resistance in PCOS patients, our study aimed to evaluate the efficacy of the integrative treatment with D-chiro-inositol (DCI) (500 mg die, per os, for 12 weeks) on hormonal parameters and insulin sensitivity in a group of overweight/obese PCOS patients (body mass index; BMI > 26). After the treatment, interval several endocrine parameters improved (luteinizing hormone [LH], LH/follicle stimulating hormone [FSH], androstenedione and insulin), insulin response to oral glucose tolerance test reported the significant improvement of insulin sensitivity as well as the gonadotropin-releasing hormone (GnRH)-induced (10 µg, in bolus) LH response. BMI decreased, though no lifestyle modification was requested. When data were analyzed according to the presence or absence of first-grade diabetic relatives, PCOS patients with diabetic relatives showed greater improvement after DCI administration. In conclusion DCI administration is effective in restoring better insulin sensitivity and an improved hormonal pattern in obese hyperinsulinemic PCOS patients, in particular, in hyperinsulinemic PCOS patients who have diabetic relatives.

  15. Impact of Bariatric Surgery on Heme Oxygenase-1, Inflammation, and Insulin Resistance in Morbid Obesity with Obstructive Sleep Apnea.

    PubMed

    Tirado, Raquel; Masdeu, Maria José; Vigil, Laura; Rigla, Mercedes; Luna, Alexis; Rebasa, Pere; Pareja, Rocío; Hurtado, Marta; Caixàs, Assumpta

    2017-09-01

    Morbid obesity and obstructive sleep apnea (OSA) interact at an inflammatory level. Bariatric surgery reduces inflammatory responses associated with obesity. Heme oxygenase-1 (HO-1) is an enzyme with anti-inflammatory properties, which might be increased in morbid obesity or OSA. We studied morbidly obese patients with OSA to determine: (a) HO-1 plasma concentrations according to OSA severity and their relationship with insulin resistance and inflammation and (b) the impact of bariatric surgery on HO-1 and parameters of insulin resistance and inflammation. We analyzed the homeostasis model insulin resistance index (HOMA) and plasma concentrations of HO-1, tumor necrosis factor alpha, interleukin-6, interleukin-1-beta, C reactive protein (CRP), and adiponectin according to polysomnography findings in 66 morbidly obese patients before bariatric surgery and 12 months after surgery. Before surgery, HO-1 plasma concentrations were similar in three groups of patients with mild, moderate, and severe OSA, and correlated with HOMA (r = 0.27, p = 0.02). Twelve months after surgery, low-grade inflammation and insulin resistance had decreased in all the groups, but HO-1 plasma concentration had decreased only in the severe OSA group (p = 0.02). In this group, the reduction in HO-1 correlated with a reduction in CRP concentrations (r = 0.43, p = 0.04) and with improved HOMA score (r = 0.37, p = 0.03). Bariatric surgery decreases HO-1 concentrations in morbid obesity with severe OSA, and this decrease is associated with decreases in insulin resistance and in inflammation.

  16. Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity

    PubMed Central

    Eisenstein, Sarah A.; Gredysa, Danuta M.; Antenor–Dorsey, Jo Ann; Green, Leonard; Arbeláez, Ana Maria; Koller, Jonathan M.; Black, Kevin J.; Perlmutter, Joel S.; Moerlein, Stephen M.; Hershey, Tamara

    2015-01-01

    Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic

  17. Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity.

    PubMed

    Eisenstein, Sarah A; Gredysa, Danuta M; Antenor-Dorsey, Jo Ann; Green, Leonard; Arbeláez, Ana Maria; Koller, Jonathan M; Black, Kevin J; Perlmutter, Joel S; Moerlein, Stephen M; Hershey, Tamara

    2015-01-01

    Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic

  18. Emerging Perspectives on Essential Amino Acid Metabolism in Obesity and the Insulin-Resistant State12

    PubMed Central

    Adams, Sean H.

    2011-01-01

    Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well known and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. Although the central role of proper blood sugar control in maintaining metabolic health is well established, recent developments have begun to shed light on associations between compromised insulin action [obesity, prediabetes, and type 2 diabetes mellitus (T2DM)] and altered intermediary metabolism of fats and amino acids. For amino acids, changes in blood concentrations of select essential amino acids and their derivatives, in particular BCAA, sulfur amino acids, tyrosine, and phenylalanine, are apparent with obesity and insulin resistance, often before the onset of clinically diagnosed T2DM. This review provides an overview of these changes and places recent observations from metabolomics research into the context of historical reports in the areas of biochemistry and nutritional biology. Based on this synthesis, a model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+). PMID:22332087

  19. Irisin and its relation to insulin resistance and puberty in obese children: a longitudinal analysis.

    PubMed

    Reinehr, Thomas; Elfers, Clinton; Lass, Nina; Roth, Christian L

    2015-05-01

    Irisin is a recently identified myokine affecting metabolic and glucose homeostasis. However, the role of irisin in obesity and its metabolic consequences are controversial, and data in children are scarce. To study the relationships between irisin, insulin resistance, and puberty before and after weight loss in obese children with and without impaired glucose tolerance. One-year follow-up study in obese children participating in a lifestyle intervention. Primary care. Forty obese children and 20 normal-weight children of similar age, gender, and pubertal stage. A 1-year outpatient intervention program based on exercise, behavior, and nutrition therapy. Fasting serum irisin, weight status (body mass index [BMI] SD score), and the following parameters of the metabolic syndrome: insulin resistance index (homeostasis model of assessment), blood pressure, and lipids. The irisin levels were the highest in obese children with impaired glucose tolerance, followed by obese children with normal glucose tolerance, and levels were lowest in normal-weight children (P < .001). In a multiple linear regression analysis, baseline irisin was significantly associated with pubertal stage, high-density lipoprotein-cholesterol, and homeostasis model of assessment, but not to age, gender, BMI, or any other parameter of the metabolic syndrome. The irisin concentrations were significantly (P = .010) lower in the prepubertal compared to the pubertal children. In longitudinal analyses, changes of irisin were significantly associated with entry into puberty, change of fasting glucose, and 2-hour glucose in an oral glucose tolerance test, but not with change of BMI or any other parameter. Irisin levels are related to pubertal stage and insulin resistance but not to weight status in childhood.

  20. Intermuscular and perimuscular fat expansion in obesity correlates with skeletal muscle T cell and macrophage infiltration and insulin resistance

    PubMed Central

    Khan, Ilvira M.; Dai Perrard, Xiao-Yuan; Brunner, Gerd; Lui, Hua; Sparks, Lauren M.; Smith, Steven R.; Wang, Xukui; Shi, Zheng-Zheng; Lewis, Dorothy E.; Wu, Huaizhu; Ballantyne, Christie M.

    2015-01-01

    Background/Objectives Limited numbers of studies demonstrated obesity-induced macrophage infiltration in skeletal muscle (SM), but dynamics of immune cell accumulation and contribution of T cells to SM insulin resistance are understudied. Subjects/Methods T cells and macrophage markers were examined in SM of obese humans by RT-PCR. Mice were fed high-fat diet (HFD) for 2–24 weeks, and time course of macrophage and T cell accumulation was assessed by flow cytometry and quantitative RT-PCR. Extramyocellular adipose tissue (EMAT) was quantified by high-resolution micro-CT, and correlation to T cell number in SM was examined. CD11a−/− mice and C57BL/6 mice were treated with CD11a-neutralizing antibody to determine the role of CD11a in T cell accumulation in SM. To investigate the involvement JAK/STAT, the major pathway for T helper I (TH1) cytokine IFNγ? in SM and adipose tissue inflammation and insulin resistance, mice were treated with a JAK1/JAK2 inhibitor, baricitinib. Results Macrophage and T cells markers were upregulated in SM of obese compared with lean humans. SM of obese mice had higher expression of inflammatory cytokines, with macrophages increasing by 2 weeks on HFD and T cells increasing by 8 weeks. The immune cells were localized in EMAT. Micro-CT revealed that EMAT expansion in obese mice correlated with T cell infiltration and insulin resistance. Deficiency or neutralization of CD11a reduced T cell accumulation in SM of obese mice. T cells polarized into a proinflammatory TH1 phenotype, with increased STAT1 phosphorylation in SM of obese mice. In vivo inhibition of JAK/STAT pathway with baricitinib reduced T cell numbers and activation markers in SM and adipose tissue and improved insulin resistance in obese mice. Conclusions Obesity-induced expansion of EMAT in SM was associated with accumulation and proinflammatory polarization of T cells, which may regulate SM metabolic functions through paracrine mechanisms. Obesity-associated SM

  1. Zinc-α2-Glycoprotein Expression in Adipose Tissue of Obese Postmenopausal Women before and after Weight Loss with and without Exercise

    PubMed Central

    Ge, Shealinna; Ryan, Alice S.

    2014-01-01

    Objective Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the regulation of adipose tissue metabolism due to its negative association with obesity and insulin resistance. The purpose of this study is to investigate the relationships between adipose tissue ZAG expression and central obesity, and the effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX+WL) on ZAG expression. Design and Methods A six-month, longitudinal study of 33 healthy, overweight or obese postmenopausal women (BMI: 25–46 kg/m2) was conducted. Abdominal and gluteal adipose tissue samples were obtained before and after AEX+WL (n=17) and WL (n=16). ZAG expression was determined by RT-PCR. Results Prior to interventions, abdominal ZAG expression was negatively correlated with visceral fat (r=−0.50, P<0.005), sagittal diameter (r=−0.42, P<0.05), and positively related to VO2max (r=0.37, P<0.05). Gluteal ZAG expression was negatively correlated with weight, fat-free mass, visceral fat, resting metabolic rate, and fasting insulin (r=−0.39 to −0.50, all P<0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after AEX+WL and 11% after WL. Gluteal ZAG mRNA levels also did not change significantly with AEX+WL and WL. Conclusions Abdominal ZAG expression may be important in central fat accumulation and fitness that modestly but not significantly increases with weight reduction alone or with aerobic training in obese postmenopausal women. PMID:24929893

  2. Is salivary gland function altered in noninsulin-dependent diabetes mellitus and obesity-insulin resistance?

    PubMed

    Ittichaicharoen, Jitjiroj; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2016-04-01

    Salivary gland dysfunction in several systemic diseases has been shown to decrease the quality of life in patients. In non-insulin dependent diabetes mellitus (NIDDM), inadequate salivary gland function has been evidenced to closely associate with this abnormal glycemic control condition. Although several studies demonstrated that NIDDM has a positive correlation with impaired salivary gland function, including decreased salivary flow rate, some studies demonstrated contradictory findings. Moreover, the changes of the salivary gland function in pre-diabetic stage known as insulin resistance are still unclear. The aim of this review is to comprehensively summarize the current evidence from in vitro, in vivo and clinical studies regarding the relationship between NIDDM and salivary gland function, as well as the correlation between obesity and salivary gland function. Consistent findings as well as controversial reports and the mechanistic insights regarding the effect of NIDDM and obesity-insulin resistance on salivary gland function are also presented and discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The triglyceride-to-HDL cholesterol ratio: association with insulin resistance in obese youths of different ethnic backgrounds.

    PubMed

    Giannini, Cosimo; Santoro, Nicola; Caprio, Sonia; Kim, Grace; Lartaud, Derek; Shaw, Melissa; Pierpont, Bridget; Weiss, Ram

    2011-08-01

    We evaluated whether the triglyceride-to-HDL cholesterol (TG/HDL-C) ratio is associated with insulin resistance (IR) in a large multiethnic cohort of obese youths. Obese youths (1,452) had an oral glucose tolerance test and a fasting lipid profile. Insulin sensitivity was estimated using the whole body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA)-IR and evaluated, in a subgroup of 146 obese youths, by the hyperinsulinemic-euglycemic clamp. The cohort was divided by ethnicity (612 whites, 357 Hispanics, and 483 African Americans) and then stratified into ethnicity-specific tertiles of TG/HDL-C ratio. Differences across tertiles were evaluated, and the association between the TG/HDL-C ratio and insulin sensitivity (WBISI) was defined by a multiple stepwise linear regression analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was determined to calculate the TG/HDL-C ratio cutoff to identify insulin-resistant subjects by ethnicity. In each ethnic group and across rising tertiles of TG/HDL-C ratio, insulin sensitivity (WBISI) progressively decreased, whereas 2-h glucose and the AUC-glucose progressively increased. The cutoff for TG/HDL-C ratio was 2.27, and the odds of presenting with IR, in youths with TG/HDL-C ratio higher than the cutoff, was 6.023 (95% CI 2.798-12.964; P < 0.001) in white girls and boys, whereas for both Hispanics and African Americans the AUC-ROCs were not significant, thus not allowing the calculation of an optimal cutoff TG/HDL-C value. The TG/HDL-C ratio is associated with IR mainly in white obese boys and girls and thus may be used with other risk factors to identify subjects at increased risk of IR-driven morbidity.

  4. Impact of blood glucose, diabetes, insulin, and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT.

    PubMed

    Büsing, Karen A; Schönberg, Stefan O; Brade, Joachim; Wasser, Klaus

    2013-02-01

    Chronically altered glucose metabolism interferes with (18)F-FDG uptake in malignant tissue and healthy organs and may therefore lower tumor detection in (18)F-FDG PET/CT. The present study assesses the impact of elevated blood glucose levels (BGL), diabetes, insulin treatment, and obesity on (18)F-FDG uptake in tumors and biodistribution in normal organ tissues. (18)F-FDG PET/CT was analyzed in 90 patients with BGL ranging from 50 to 372 mg/dl. Of those, 29 patients were diabetic and 21 patients had received insulin prior to PET/CT; 28 patients were obese with a body mass index >25. The maximum standardized uptake value (SUV(max)) of normal organs and the main tumor site was measured. Differences in SUV(max) in patients with and without elevated BGLs, diabetes, insulin treatment, and obesity were compared and analyzed for statistical significance. Increased BGLs were associated with decreased cerebral FDG uptake and increased uptake in skeletal muscle. Diabetes and insulin diminished this effect, whereas obesity slightly enhanced the outcome. Diabetes and insulin also increased the average SUV(max) in muscle cells and fat, whereas the mean cerebral SUV(max) was reduced. Obesity decreased tracer uptake in several healthy organs by up to 30%. Tumoral uptake was not significantly influenced by BGL, diabetes, insulin, or obesity. Changes in BGLs, diabetes, insulin, and obesity affect the FDG biodistribution in muscular tissue and the brain. Although tumoral uptake is not significantly impaired, these findings may influence the tumor detection rate and are therefore essential for diagnosis and follow-up of malignant diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Body fat distribution, serum glucose, lipid and insulin response to meals in Alström syndrome.

    PubMed

    Paisey, R B; Hodge, D; Williams, K

    2008-06-01

    Alström syndrome is an autosomal recessive condition characterized by obesity, insulin resistance and hypertriglyceridaemia. Responses to fat and carbohydrate ingestion are important in planning dietetic advice and may help to explain the mechanism of metabolic disorder in the syndrome. After a 12-h fast, five Alström subjects received a 3.1 MJ (742 kcal), 75.8% fat breakfast on day 1, and a 3.3 MJ (794 kcal), 77.5% carbohydrate breakfast on day 2. Serum glucose, triglyceride and insulin levels were measured at baseline, and 2 and 3.5 h post-meal. Abdominal computerized tomography in three subjects and magnetic resonance imaging in one demonstrated distribution of abdominal fat. Body fat was distributed subcutaneously, as well as viscerally. There were no changes in serum glucose, insulin or triglycerides after the high fat meal. Triglycerides remained stable after the high carbohydrate meal but glucose and log insulin levels increased [8.4 +/- 4.1 to 13.4 +/- 6.9 mmol L(-1) (P < 0.05) and 2.6 +/- 0.27 to 3.15 +/- 0.42 pmol L(-1) (P < 0.05), respectively]. Dietetic advice in Alström syndrome must include calorie restriction to reduce obesity, which is predominantly subcutaneous. This study has shown that low carbohydrate advice may prove more effective than fat restriction in control of hyperglycaemia and hyperinsulinism. A single high energy meal does not exacerbate hypertriglyceridaemia.

  6. The transcriptional coactivators p/CIP and SRC-1 control insulin resistance through IRS1 in obesity models.

    PubMed

    Wang, Zhiyong; Shah, O Jameel; Hunter, Tony

    2012-01-01

    Three p160 family members, p/CIP, SRC1, and TIF2, have been identified as transcriptional coactivators for nuclear hormone receptors and other transcription factors in vitro. In a previous study, we reported initial characterization of the obesity-resistant phenotypes of p/CIP and SRC-1 double knockout (DKO) mice, which exhibit increased energy expenditure, and suggested that nuclear hormone receptor target genes were involved in these phenotypes. In this study, we demonstrate that p/CIP and SRC1 control insulin signaling in a cell-autonomous manner both in vitro and in vivo. Genetic deletion of p/CIP and SRC-1 increases glucose uptake and enhances insulin sensitivity in both regular chow- and high fat diet-fed DKO mice despite increased food intake. Interestingly, we discover that loss of p/CIP and SRC-1 results in resistance to age-related obesity and glucose intolerance. We show that expression levels of a key insulin signaling component, insulin receptor substrate 1 (IRS1), are significantly increased in two cell lines representing fat and muscle lineages with p/CIP and SRC-1 deletions and in white adipose tissue and skeletal muscle of DKO mice; this may account for increased glucose metabolism and insulin sensitivity. This is the first evidence that the p160 coactivators control insulin signaling and glucose metabolism through IRS1. Therefore, our studies indicate that p/CIP and SRC-1 are potential therapeutic targets not only for obesity but also for diabetes.

  7. The Transcriptional Coactivators p/CIP and SRC-1 Control Insulin Resistance through IRS1 in Obesity Models

    PubMed Central

    Wang, Zhiyong; Shah, O. Jameel; Hunter, Tony

    2012-01-01

    Three p160 family members, p/CIP, SRC1, and TIF2, have been identified as transcriptional coactivators for nuclear hormone receptors and other transcription factors in vitro. In a previous study, we reported initial characterization of the obesity-resistant phenotypes of p/CIP and SRC-1 double knockout (DKO) mice, which exhibit increased energy expenditure, and suggested that nuclear hormone receptor target genes were involved in these phenotypes. In this study, we demonstrate that p/CIP and SRC1 control insulin signaling in a cell-autonomous manner both in vitro and in vivo. Genetic deletion of p/CIP and SRC-1 increases glucose uptake and enhances insulin sensitivity in both regular chow- and high fat diet-fed DKO mice despite increased food intake. Interestingly, we discover that loss of p/CIP and SRC-1 results in resistance to age-related obesity and glucose intolerance. We show that expression levels of a key insulin signaling component, insulin receptor substrate 1 (IRS1), are significantly increased in two cell lines representing fat and muscle lineages with p/CIP and SRC-1 deletions and in white adipose tissue and skeletal muscle of DKO mice; this may account for increased glucose metabolism and insulin sensitivity. This is the first evidence that the p160 coactivators control insulin signaling and glucose metabolism through IRS1. Therefore, our studies indicate that p/CIP and SRC-1 are potential therapeutic targets not only for obesity but also for diabetes. PMID:22859932

  8. The effects of short-term overfeeding on insulin action in lean and reduced-obese individuals.

    PubMed

    Cornier, Marc-Andre; Bergman, Bryan C; Bessesen, Daniel H

    2006-09-01

    Insulin resistance is clearly associated with obesity. However, the role of excess energy intake per se as opposed to increased fat mass in the development of insulin resistance has not been clearly defined. It may be that the nutrient load provided by short-term overfeeding is sufficient to induce measurable changes in insulin action in skeletal muscle and the liver. We examined the effects of 3 days of overfeeding on insulin action and glucose kinetics in 13 lean (body mass index, 20.9 +/- 2.4 kg/m(2); 6 men, 7 women) and 9 reduced-obese (RO) (body mass index, 29.1 +/- 2.2 kg/m(2); 4 men, 5 women) individuals. A two-step euglycemic hyperinsulinemic clamp study (5 and 40 mU m(-2) min(-1)) with a primed, constant infusion of [6,6-(2)H(2)]glucose was performed after 3 days of a weight-maintenance diet and again after 3 days of overfeeding by 50% (50% carbohydrate, 30% fat, 20% protein). At baseline, lean individuals were more insulin sensitive, as measured by glucose infusion rate, than RO individuals (12.08 +/- 0.8 vs 7.62 +/- 1.0 mg x kg(-1) x min(-1), P < .01) with lean women being more insulin sensitive than lean men (P < .01). Overfeeding resulted in a reduction in glucose infusion rate in lean women (13.37 +/- 1.3 to 11.42 +/- 1.0 mg x kg(-1) x min(-1), P < .05), but no change was noted in lean men or RO individuals. Basal and insulin-stimulated glucose disposal remained unchanged with overfeeding in all groups. Low-dose insulin suppression of endogenous glucose production was impaired after overfeeding in lean women (euenergetic, 1.92 +/- 0.36 to 0.36 +/- 0.16 mg x kg(-1) x min(-1); overfeeding: 2.13 +/- 0.17 to 0.86 +/- 0.12 mg x kg(-1) x min(-1); P = .04) but remained unchanged in the other groups. These findings demonstrate that insulin action is reduced in lean, obese-resistant women after short-term overfeeding primarily because of an inhibition of insulin-mediated suppression of endogenous glucose production, whereas short-term overfeeding does not

  9. Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice.

    PubMed

    Li, B; Nolte, L A; Ju, J S; Han, D H; Coleman, T; Holloszy, J O; Semenkovich, C F

    2000-10-01

    To determine whether uncoupling respiration from oxidative phosphorylation in skeletal muscle is a suitable treatment for obesity and type 2 diabetes, we generated transgenic mice expressing the mitochondrial uncoupling protein (Ucp) in skeletal muscle. Skeletal muscle oxygen consumption was 98% higher in Ucp-L mice (with low expression) and 246% higher in Ucp-H mice (with high expression) than in wild-type mice. Ucp mice fed a chow diet had the same food intake as wild-type mice, but weighed less and had lower levels of glucose and triglycerides and better glucose tolerance than did control mice. Ucp-L mice were resistant to obesity induced by two different high-fat diets. Ucp-L mice fed a high-fat diet had less adiposity, lower levels of glucose, insulin and cholesterol, and an increased metabolic rate at rest and with exercise. They were also more responsive to insulin, and had enhanced glucose transport in skeletal muscle in the setting of increased muscle triglyceride content. These data suggest that manipulating respiratory uncoupling in muscle is a viable treatment for obesity and its metabolic sequelae.

  10. The relationship of breakfast skipping and type of breakfast consumed with overweight/obesity, abdominal obesity, other cardiometabolic risk factors and the metabolic syndrome in young adults. NHANES 1999-2006

    USDA-ARS?s Scientific Manuscript database

    The goal of this study was to examine the association between breakfast skipping and type of breakfast consumed with overweight /obesity, abdominal obesity, other cardiometabolic risk factors and the metabolic syndrome. Three breakfast groups were identified (breakfast skippers, ready-to-eat-cereal ...

  11. Nesfatin-1 in childhood and adolescent obesity and its association with food intake, body composition and insulin resistance.

    PubMed

    Anwar, Ghada M; Yamamah, Gamal; Ibrahim, Amani; El-Lebedy, Dalia; Farid, Tarek M; Mahmoud, Rasha

    2014-01-10

    Nesfatin-1 is an anorexigenic peptide that controls feeding behavior and glucose homeostasis. However, there is little data that exists regarding nesfatin-1 secretion in obese children and young adolescents. The aim of this study is to investigate serum nesfatin-1 in childhood and adolescent obesity and to study potential correlations with food intake, anthropometric indices, body composition and insulin resistance. Forty obese children and adolescents and 40 healthy control subjects were studied. Anthropometric measurements were assessed, dietary food intake was evaluated based on 3-days food record and body composition indices were evaluated using bioelectrical impedance analysis. Lipid profile, fasting blood sugar, fasting insulin and HOMA-IR were measured. Fasting serum nesfatin-1 was quantitatively assayed by ELISA. Serum nesfatin-1 was significantly higher in obese group (2.49±1.96 ng/ml) than in control group (0.70±0.81 ng/ml), P=0.001. Positive correlations with serum insulin (P=0.001), HOMA-IR (P=0.000), BMI-SDS (P=0.04), body fat % (P=0.000), fat mass (P=0.000), fat free mass (P=0.03), CHO % (P=0.000), and saturated fat % (P=0.01) were found. While significant negative correlation with protein % (P=0.000) was observed. In conclusion, our results denote that nesfatin-1 might have an important role in regulation of food intake and pathogenesis of insulin resistance in obese children and young adolescents. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. The efficacy and tolerability of azilsartan in obese insulin-resistant mice with left ventricular pressure overload.

    PubMed

    Tarikuz Zaman, A K M; McLean, Danielle L; Sobel, Burton E

    2013-10-01

    Angiotensin II receptor blockers (ARBs) are used widely for the treatment of heart failure. However, their use in obese and insulin-resistant patients remains controversial. To clarify their potential efficacy in these conditions, we administered azilsartan medoxomil (azilsartan), a prodrug of an angiotensin II receptor blocker to mice fed a high-fat diet (HFD) with left ventricular (LV) pressure overload (aortic banding). LV fibrosis (hydroxyproline), cardiac plasminogen activator inhibitor-1 (PAI-1; a marker of profibrosis), and creatine kinase (a marker of myocardial viability and energetics) were assessed. LV wall thickness and cardiac function were assessed echocardiographically. Mice given a HFD were obese and insulin resistant. Their LV hypertrophy was accompanied by greater LV PAI-1 and reduced LV creatine kinase compared with normal diet controls. Drug treatment reduced LV wall thickness, hypertrophy, and PAI-1 and increased cardiac output after aortic banding compared with results in HFD vehicle controls. Thus, azilsartan exerted favorable biological effects on the hearts of obese insulin-resistant mice subjected to LV pressure overload consistent with its potential utility in patients with analogous conditions.

  13. Role of microRNAs on adipogenesis, chronic low-grade inflammation, and insulin resistance in obesity.

    PubMed

    Cruz, Kyria Jayanne Clímaco; de Oliveira, Ana Raquel Soares; Morais, Jennifer Beatriz Silva; Severo, Juliana Soares; Marreiro PhD, Dilina do Nascimento

    2017-03-01

    The aim of this review was to convey updated information on the role of microRNAs in adipogenesis, chronic low-grade inflammation, and insulin resistance in obesity. Obesity is a chronic disease characterized by the presence of metabolic disorders (e.g., low-grade chronic inflammation), which contributes to the manifestation of insulin resistance. Diverse molecular mechanisms have been implicated in the development of these disorders, and microRNAs stand out as a contributing factor. They are a class of noncoding RNAs that regulate the expression of genes by inducing cleavage of mRNAs or via inhibition of protein translation. It is important to point out that obese individuals show alterations in the expression of microRNAs favoring manifestation of the metabolic disorders present in these patients, and these alterations may be reversed by the loss of weight. Therefore, microRNAs may be regarded as potential biomarkers of obesity-related disorders. Further studies on this topic may advance the understanding of the molecular basis of obesity, including the participation of microRNAs in the pathogenesis of this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Ganoderic Acid A improves high fat diet-induced obesity, lipid accumulation and insulin sensitivity through regulating SREBP pathway.

    PubMed

    Zhu, Jing; Jin, Jie; Ding, Jiexia; Li, Siying; Cen, Panpan; Wang, Keyi; Wang, Hai; Xia, Junbo

    2018-06-25

    Obesity and its major co-morbidity, type 2 diabetes, have been an alarming epidemic prevalence without an effective treatment available. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. Therefore, inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Here, we identify a small molecule, Ganoderic Acid A (GAA), inhibits the SREBP expression and decreases the cellular levels of cholesterol and fatty acid in vitro. GAA also ameliorates body weight gain and fat accumulation in liver or adipose tissues, and improves serum lipid levels and insulin sensitivity in high fat diet (HFD)-induced obese mice. Consistently, GAA regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Taken together, GAA could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance. Copyright © 2018. Published by Elsevier B.V.

  15. Early Mitochondrial Adaptations in Skeletal Muscle to Diet-Induced Obesity Are Strain Dependent and Determine Oxidative Stress and Energy Expenditure But Not Insulin Sensitivity

    PubMed Central

    Sena, Sandra; Sloan, Crystal; Tebbi, Ali; Han, Yong Hwan; O'Neill, Brian T.; Cooksey, Robert C.; Jones, Deborah; Holland, William L.; McClain, Donald A.; Abel, E. Dale

    2012-01-01

    This study sought to elucidate the relationship between skeletal muscle mitochondrial dysfunction, oxidative stress, and insulin resistance in two mouse models with differential susceptibility to diet-induced obesity. We examined the time course of mitochondrial dysfunction and insulin resistance in obesity-prone C57B and obesity-resistant FVB mouse strains in response to high-fat feeding. After 5 wk, impaired insulin-mediated glucose uptake in skeletal muscle developed in both strains in the absence of any impairment in proximal insulin signaling. Impaired mitochondrial oxidative capacity preceded the development of insulin resistant glucose uptake in C57B mice in concert with increased oxidative stress in skeletal muscle. By contrast, mitochondrial uncoupling in FVB mice, which prevented oxidative stress and increased energy expenditure, did not prevent insulin resistant glucose uptake in skeletal muscle. Preventing oxidative stress in C57B mice treated systemically with an antioxidant normalized skeletal muscle mitochondrial function but failed to normalize glucose tolerance and insulin sensitivity. Furthermore, high fat-fed uncoupling protein 3 knockout mice developed increased oxidative stress that did not worsen glucose tolerance. In the evolution of diet-induced obesity and insulin resistance, initial but divergent strain-dependent mitochondrial adaptations modulate oxidative stress and energy expenditure without influencing the onset of impaired insulin-mediated glucose uptake. PMID:22510273

  16. The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance.

    PubMed

    Pincelli, A I; Brunani, A; Scacchi, M; Dubini, A; Borsotti, R; Tibaldi, A; Pasqualinotto, L; Maestri, E; Cavagnini, F

    2001-01-01

    The tumor necrosis factor alpha (TNF-alpha) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased cardiovascular risk, and insulin resistance. On the other hand, GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA patients. No information is presently available on the relationship between serum TNF-alpha levels and insulin sensitivity in GHDA. We compared the serum TNF-alpha levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects. The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.30 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recombinant human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear regression analysis showed no correlation between TNF-alpha and M values (see text) in all patient groups. These data indicate

  17. Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome.

    PubMed

    Cheang, Kai I; Sistrun, Sakita N; Morel, Kelley S; Nestler, John E

    2016-01-01

    Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS ( n = 16) and normal ( n = 15) women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUC DCI-IPG ), AUC insulin , and AUC DCI-IPG /AUC insulin were measured during a 2 hr OGTT at baseline and 8 weeks. Results. PCOS women had lower AUC DCI-IPG /AUC insulin at baseline and a significant relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0003), which was not present in controls. Weight loss was similar between PCOS (-4.08 kg) and normal women (-4.29 kg, p = 0.6281). Weight loss in PCOS women did not change the relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0100), and this relationship remained absent in control women. Conclusion. The association between AUC DCI-IPG /AUC insulin and insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity.

  18. Characterization of beta-cell mass and insulin resistance in diet-induced obese and diet-resistant rats.

    PubMed

    Paulsen, Sarah J; Jelsing, Jacob; Madsen, Andreas N; Hansen, Gitte; Lykkegaard, Kirsten; Larsen, Leif K; Larsen, Philip J; Levin, Barry E; Vrang, Niels

    2010-02-01

    The selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats represent a polygenetic animal model mimicking most clinical variables characterizing the human metabolic syndrome. When fed a high-energy (HE) diet DIO rats develop visceral obesity, dyslipidemia, hyperinsulinemia, and insulin resistance but never frank diabetes. To improve our understanding of the underlying cause for the deteriorating glucose and insulin parameters, we have investigated possible adaptive responses in DIO and DR rats at the level of the insulin-producing beta-cells. At the time of weaning, DR rats were found to have a higher body weight and beta-cell mass compared to DIO rats, and elevated insulin and glucose responses to an oral glucose load. However, at 2.5 months of age, and for the remaining study period, the effect of genotype became evident: the chow-fed DIO rats steadily increased their body weight and beta-cell mass, as well as insulin and glucose levels compared to the DR rats. HE feeding affected both DIO and DR rats leading to an increased body weight and an increased beta-cell mass. Interestingly, although the beta-cell mass in DR rats and chow-fed DIO rats appeared to constantly increase with age, the beta-cell mass in the HE-fed DIO rats did not continue to do so. This might constitute part of an explanation for their reduced glucose tolerance. Collectively, the data support the use of HE-fed DIO rats as a model of human obesity and insulin resistance, and accentuate its relevance for studies examining the benefit of pharmaceutical compounds targeting this disease complex.

  19. Obesity and insulin resistance are associated with reduced activity in core memory regions of the brain.

    PubMed

    Cheke, Lucy G; Bonnici, Heidi M; Clayton, Nicola S; Simons, Jon S

    2017-02-01

    Increasing research in animals and humans suggests that obesity may be associated with learning and memory deficits, and in particular with reductions in episodic memory. Rodent models have implicated the hippocampus in obesity-related memory impairments, but the neural mechanisms underlying episodic memory deficits in obese humans remain undetermined. In the present study, lean and obese human participants were scanned using fMRI while completing a What-Where-When episodic memory test (the "Treasure-Hunt Task") that assessed the ability to remember integrated item, spatial, and temporal details of previously encoded complex events. In lean participants, the Treasure-Hunt task elicited significant activity in regions of the brain known to be important for recollecting episodic memories, such as the hippocampus, angular gyrus, and dorsolateral prefrontal cortex. Both obesity and insulin resistance were associated with significantly reduced functional activity throughout the core recollection network. These findings indicate that obesity is associated with reduced functional activity in core brain areas supporting episodic memory and that insulin resistance may be a key player in this association. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance.

    PubMed

    Du, Caiqi; Zhang, Cai; Wu, Wei; Liang, Yan; Wang, Anru; Wu, Shimin; Zhao, Yue; Hou, Ling; Ning, Qin; Luo, Xiaoping

    2018-04-25

    A novel bioactive peptide, mitochondrial-derived peptide (MOTS-c), has recently attracted attention as a potential prevention or therapeutic option for obesity and type 2 diabetes mellitus (T2DM). MOTS-c profiles have not yet been reported in human obesity and T2DM. We aimed to determine circulating MOTS-c levels in obesity and explore the association between MOTS-c levels and various metabolic parameters. In this case-control study, 40 obese children and adolescents (27 males) and 57 controls (40 males) were recruited in the Hubei Province of China in 2017. Circulating MOTS-c levels were measured, clinical data (e.g., glucose, insulin and lipid profile) were recorded, and anthropometric measurements were performed. Finally, we investigated correlations between MOTS-c levels and related variables. MOTS-c levels were significantly decreased in the obese group compared with the control group (472.61 ± 22.83 ng/mL vs. 561.64 ± 19.19 ng/mL, p < 0.01). After classification by sex, MOTS-c levels were significantly decreased in obese male children and adolescents compared to their counterparts (465.26 ± 24.53 ng/mL vs. 584.07 ± 21.18 ng/mL, p < 0.001), while they were comparable between the obese and healthy female subjects (487.89 ± 49.77 ng/mL vs. 508.85 ± 38.76 ng/mL, p > 0.05). Further, MOTS-c levels were negatively correlated with body mass index (BMI), BMI standard deviation score, waist circumference, waist-to-hip ratio, fasting insulin level, HOMA-IR, and HbA1c in the male cohort. Circulating MOTS-c levels were decreased in obese male children and adolescents and correlated with markers of insulin resistance and obesity. This article is protected by copyright. All rights reserved.

  1. A review of obesity, insulin resistance, and the role of exercise in breast cancer patients.

    PubMed

    Ghose, Abhimanyu; Kundu, Ria; Toumeh, Anis; Hornbeck, Catherine; Mohamed, Iman

    2015-01-01

    Breast cancer, the most common female malignancy in the world, has a strong association with obesity and insulin resistance. The importance of these risk factors goes up significantly in patients already affected by this cancer as they negatively affect the prognosis, recurrence rate, and survival by various mechanisms. The literature on the role of physical activity and aerobic exercise on modifying the above risks is debatable with data both for and against it. In this article, we have reviewed the risks of obesity and insulin resistance in breast cancer patients and the controversy associated with the impact of exercise. Ultimately, we have concluded that a randomized control trial is necessary with an individualized aerobic exercise program for a minimum duration of 20 wk on breast cancer patients, who are undergoing or recently completed chemotherapy, to study its effects on insulin resistance, weight, and clinical outcome.

  2. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    PubMed

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. © 2015 Authors; published by Portland Press Limited.

  3. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    PubMed Central

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

  4. Smad3 deficiency protects mice from obesity-induced podocyte injury that precedes insulin resistance.

    PubMed

    Sun, Yu B Y; Qu, Xinli; Howard, Victor; Dai, Lie; Jiang, Xiaoyun; Ren, Yi; Fu, Ping; Puelles, Victor G; Nikolic-Paterson, David J; Caruana, Georgina; Bertram, John F; Sleeman, Mark W; Li, Jinhua

    2015-08-01

    Signaling by TGF-β/Smad3 plays a key role in renal fibrosis. As obesity is one of the major risk factors of chronic and end-stage renal disease, we studied the role of Smad3 signaling in the pathogenesis of obesity-related renal disease. After switching to a high fat diet, the onset of Smad3 C-terminal phosphorylation, increase in albuminuria, and the early stages of peripheral and renal insulin resistance occurred at 1 day, and 4 and 8 weeks, respectively, in C57BL/6 mice. The loss of synaptopodin, a functional marker of podocytes, and phosphorylation of the Smad3 linker region (T179 and S213) appeared after 4 weeks of the high fat diet. This suggests a temporal pattern of Smad3 signaling activation leading to kidney injury and subsequent insulin resistance in the development of obesity-related renal disease. In vivo, Smad3 knockout attenuated the high fat diet-induced proteinuria, renal fibrosis, overall podocyte injury, and mitochondrial dysfunction in podocytes. In vitro palmitate caused a rapid activation of Smad3 in 30 min, loss of synaptopodin in 2 days, and impaired insulin signaling in 3 days in isolated mouse podocytes. Blockade of either Smad3 phosphorylation by SIS3 (a Smad3 inhibitor) or T179 phosphorylation by flavopiridol (a CDK9 inhibitor) prevented the palmitate-induced loss of synaptopodin and mitochondrial function in podocytes. Thus, Smad3 signaling plays essential roles in obesity-related renal disease and may be a novel therapeutic target.

  5. Increased abdominal fat levels measured by bioelectrical impedance are associated with histological lesions of nonalcoholic steatohepatitis.

    PubMed

    Margariti, Aikaterini; Kontogianni, Meropi D; Tileli, Nafsika; Georgoulis, Michael; Deutsch, Melanie; Zafeiropoulou, Rodessa; Tiniakos, Dina; Manios, Yannis; Pectasides, Dimitrios; Papatheodoridis, George V

    2015-08-01

    Abdominal fat is considered to play an important role in nonalcoholic fatty liver disease (NAFLD), although it is not adequately studied because abdominal fat levels cannot be estimated easily. In this study, associations between abdominal obesity, as assessed by abdominal bioelectrical impedance analysis (BIA), and the characteristics of patients with NAFLD were explored. Seventy-four consecutive NAFLD patients who underwent measurement of abdominal fat levels by BIA were included. Levels of abdominal fat 12.5 or less and more than 12.5 were considered to be average and increased, respectively. The mean±SD BMI was 30±4 kg/m and the mean abdominal fat levels were 16±5, whereas 26% of patients had average abdominal fat levels. Patients with average compared with those with increased abdominal fat levels were more frequently women (50 vs. 12%, P=0.001), had lower BMI (27±3 vs. 31±4 kg/m, P<0.001), lower Homeostasis Model Assessment index (2.6±1.4 vs. 3.9±2.7, P=0.045), and lower median liver stiffness on transient elastography (5.3 vs. 6.8 kPa, P=0.025). In patients with available liver biopsy, steatohepatitis was present more frequently in patients with increased compared with average abdominal fat levels (78 vs. 38%, P=0.030) and in patients with BMI 30 or more compared with less than 30 kg/m (87 vs. 48%, P=0.033), but similar in patients with increased or normal waist circumference (67 vs. 56%, P=0.693). Average levels of abdominal fat, as assessed by abdominal BIA, are mainly present in female patients with NAFLD and are associated with a lower degree of insulin resistance. Increased abdominal fat as assessed by BIA and obesity seem to represent strong risk factors for histological steatohepatitis.

  6. Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats

    PubMed Central

    Picklo, Matthew J.; Thyfault, John P.

    2016-01-01

    Controversy exists as to whether supplementation with the antioxidants vitamin E and vitamin C blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial function and induces insulin resistance (IR), no data exist as to whether supplementation with vitamin E and vitamin C modify responses to exercise in pre-existing obesity. We tested the hypothesis that dietary supplementation with vitamin E (0.4 g α-tocopherol acetate/kg) and vitamin C (0.5 g/kg) blocks exercise-induced improvements on IR and mitochondrial content in obese rats maintained on a high-fat (45% fat energy (en)) diet. Diet-induced obese, sedentary rats had a 2-fold higher homeostasis model assessment of insulin resistance and larger insulin area under the curve following glucose tolerances test than rats fed a low-fat (10% fat en) diet. Exercising (12 weeks at 5 times per week in a motorized wheel) of obese rats normalized IR indices, an effect not modified by vitamin E and vitamin C. Vitamin E and vitamin C supplementation with exercise elevated mtDNA content in adipose and skeletal muscle to a greater extent (20%) than exercise alone in a depot-specific manner. On the other hand, vitamin C and vitamin E decreased exercise-induced increases in mitochondrial protein content for complex I (40%) and nicotinamide nucleotide transhydrogenase (35%) in a muscle-dependent manner. These data indicate that vitamin E and vitamin C supplementation in obese rodents does not modify exercise-induced improvements in insulin sensitivity but that changes in mitochondrial biogenesis and mitochondrial protein expression may be modified by antioxidant supplementation. PMID:25761734

  7. Association of perceived ethnic discrimination with general and abdominal obesity in ethnic minority groups: the HELIUS study.

    PubMed

    Schmengler, Heiko; Ikram, Umar Z; Snijder, Marieke B; Kunst, Anton E; Agyemang, Charles

    2017-05-01

    Discrimination is associated with obesity, but this may differ according to the type of obesity and ethnic group. This study examines the association of perceived ethnic discrimination (PED) with general and abdominal obesity in 5 ethnic minority groups. We used cross-sectional data from the HELIUS study, collected from 2011 to 2015. The study sample included 2297 Ghanaians, 4110 African Surinamese, 3021 South-Asian Surinamese, 3562 Turks and 3868 Moroccans aged 18-70 years residing in Amsterdam, the Netherlands. Body mass index (BMI) was used as a measure for general obesity, and waist circumference (WC) for abdominal obesity. PED was measured using the Everyday Discrimination Scale. We used linear regression models adjusted for sociodemographics, psychosocial stressors and health behaviours. In additional analysis, we used standardised variables to compare the strength of the associations. In adjusted models, PED was significantly, positively associated with BMI in the South-Asian Surinamese (β coefficient 0.338; 95% CI 0.106 to 0.570), African Surinamese (0.394; 0.171 to 0.618) and Turks (0.269; 0.027 to 0.510). For WC, a similar pattern was seen: positive associations in the South-Asian Surinamese (0.759; 0.166 to 1.353), African Surinamese (0.833; 0.278 to 1.388) and Turks (0.870; 0.299 to 1.440). When stratified by sex, we found positive associations in Surinamese women, Turkish men and Moroccan men. The strength of the associations with BMI and WC was comparable in the groups. Among the Ghanaians, no significant associations were observed. Ethnic and sex variations are observed in the association of PED with both general and abdominal obesity. Further research on psychosocial buffers and underlying biological mechanisms might help in understanding these variations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Overweight and abdominal obesity in women of childbearing age of Russian, Somali and Kurdish origin and the general Finnish population.

    PubMed

    Kinnunen, Tarja I; Skogberg, Natalia; Härkänen, Tommi; Lundqvist, Annamari; Laatikainen, Tiina; Koponen, Päivikki

    2017-05-15

    Migrant background and higher parity may increase the risk of being overweight. We compared the prevalence of overweight (body mass index ≥25 kg/m2) and abdominal obesity (waist-to-height ratio ≥0.5) between non-pregnant migrant and Finnish women aged 18-45 years. The participants were 165 Russian, 164 Somali and 179 Kurdish origin women from the cross-sectional Migrant Health and Wellbeing study. The reference group included 388 women from the general Finnish population. Body anthropometrics were measured. The main statistical methods were logistic regression adjusted for sociodemographic and reproductive variables. The unadjusted prevalence of overweight and obesity, respectively, were higher among Somali (32.9%, 30.9%, P < 0.001) and Kurdish women (41.1%, 19.5%, P < 0.001) than among Finnish women (19.9%, 9.8%). The adjusted odds ratios (95% CI) for overweight (including obesity) were 0.54 (0.33; 0.89) for Russian, 2.89 (1.66; 5.03) for Somali and 2.56 (1.64; 4.00) for Kurdish women compared with Finnish women. Kurdish women had 2.96-fold (1.75; 5.00) adjusted odds ratio for abdominal obesity compared with Finnish women. Being parous was associated with overweight and abdominal obesity among Kurdish women. Overweight and obesity were very common among Somali and Kurdish origin women. Information on diet and physical activity in these groups is needed. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  9. Childhood obesity and type 2 diabetes in India.

    PubMed

    Praveen, Pradeep A; Tandon, Nikhil

    2016-04-01

    India is witnessing an increase in the burden of childhood obesity, especially among the upper socioeconomic strata and in urban areas. Emerging literature suggests a link between childhood obesity and the diabetes epidemic in India. Asian-Indian children and adolescents are increasingly susceptible to a high percentage of body fat and abdominal adiposity. Further, they are exposed to an obesogenic environment, created by rapid urbanization and nutrition transition in India. Obese children have a higher risk of developing abnormalities that are recognized as precursors to diabetes, such as subclinical inflammation, insulin resistance and metabolic syndrome, which often track to adulthood. A review of the literature suggests the need for more longitudinal studies to improve understanding of the long-term consequences of childhood obesity in India. A life-course approach with a combination of population- and risk-based strategies is warranted, to prevent childhood obesity and curtail its consequences in adulthood.

  10. The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance.

    PubMed

    Gutiérrez Medina, Sonsoles; Gavela-Pérez, Teresa; Domínguez-Garrido, María Nieves; Gutiérrez-Moreno, Elisa; Rovira, Adela; Garcés, Carmen; Soriano-Guillén, Leandro

    2015-01-01

    Puberty can affect vitamin D levels. The goal of this study was to analyze the relation between vitamin D deficiency and puberty in obese Spanish children, along with the possible interrelation between vitamin D status and degree of insulin resistance. A cross-sectional study was carried out, in which clinical and biochemical data were gathered from 120 obese and 50 normal weight children between January 2011 and January 2013. Mean vitamin D levels were 19.5 and 31.6 ng/mL in obese pubertal and obese prepubertal children, respectively. About 75% of the obese pubertal subjects and 46% of the obese prepubertal subjects had vitamin D deficiency. Vitamin D levels were significantly lower in pubescent subjects compared with pre-pubescent subjects in summer, fall, and winter. There was no apparent relation between vitamin D levels and homeostasis model assessment index for insulin resistence (expressed in standard deviation score for sex and Tanner stage) in either puberty or pre-puberty. Puberty may be a risk factor for the vitamin D deficiency commonly found in the obese child population. This deficiency is not associated with higher insulin resistance in obese pubertal children compared with obese prepubertal children.

  11. Medical implications of obesity in horses--lessons for human obesity.

    PubMed

    Johnson, Philip J; Wiedmeyer, Charles E; Messer, Nat T; Ganjam, Venkataseshu K

    2009-01-01

    There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. © Diabetes Technology Society

  12. Medical Implications of Obesity in Horses—Lessons for Human Obesity

    PubMed Central

    Johnson, Philip J.; Wiedmeyer, Charles E.; Messer, Nat T.; Ganjam, Venkataseshu K.

    2009-01-01

    There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. PMID:20046661

  13. Response of osteocalcin and insulin resistance after a hypocaloric diet in obese patients.

    PubMed

    de Luis, D A; Perez Castrillon, J L; Aller, R; Izaola, O; Bachiller, C

    2015-06-01

    Osteocalcin is a hormone with a complex cross-talk between adipose tissue and the skeleton. The aim of the present study was to explore the change of osteocalcin, insulin resistance, and adipocytokines after hypocaloric diet in obese patients. A population of 178 obese patients was analyzed. At basal time and 2 months after the dietary intervention, weight, fat mass, body mass index, basal glucose, insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, leptin, adiponectin, IL-6, TNF alpha and osteocalcin levels were measured. After dietary treatment, BMI, weight, fat mass, waist circumference, waist to hip ratio, systolic pressure, glucose, HOMA, triglycerides, total cholesterol, leptin and LDL cholesterol decreased significantly. Osteocalcin levels have a significant decrease after weight loss (Osteocalcin (ng/ml); 9.76 ± 5.3 vs 9.31 ± 4.1: p < 0.05). In correlation analysis, a negative association was detected among osteocalcin and age, BMI, fat mass, glucose, C reactive protein, interleukin-6. In the linear regression with age-, sex-, BMI, fat mass- and insulin- adjusted, only C reactive protein concentrations are related with osteocalcin levels -0.21 (CI 95%: -0.40 -0.009). Osteocalcin decreased after a weight loss treatment. Moreover, osteocalcin levels, before and after treatment, were related in a negative way with CRP fat mass, body mass index, age and glucose levels.

  14. Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance

    PubMed Central

    McNabney, Sean M.

    2017-01-01

    Increased dietary fiber consumption has been associated with many beneficial effects, including amelioration of obesity and insulin resistance. These effects may be due to the increased production of short chain fatty acids, including propionate, acetate and butyrate, during fermentation of the dietary fiber in the colon. Indeed, oral and dietary supplementation of butyrate alone has been shown to prevent high fat-diet induced obesity and insulin resistance. This review focuses on sources of short chain fatty acids, with emphasis on sources of butyrate, mechanisms of fiber and butyrate metabolism in the gut and its protective effects on colon cancer and the peripheral effects of butyrate supplementation in peripheral tissues in the prevention and reversal of obesity and insulin resistance. PMID:29231905

  15. Unusual Suspects in the Development of Obesity-Induced Inflammation and Insulin Resistance: NK cells, iNKT cells, and ILCs.

    PubMed

    Bonamichi, Beatriz Dal Santo Francisco; Lee, Jongsoon

    2017-08-01

    The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils. Recently, however, new cell types have been shown to participate in the development of obesity-induced inflammation and insulin resistance. Some of these cell types also appear to regulate obesity. These cells are natural killer (NK) cells and innate lymphoid cells (ILCs), which are closely related, and invariant natural killer T (iNKT) cells. It should be noted that, although iNKT cells resemble NK cells in name, they are actually a completely different cell type in terms of their development and functions in immunity and metabolism. In this review, we will focus on the roles that these relatively new players in the metabolism field play in obesity-induced insulin resistance and the regulation of obesity. Copyright © 2017 Korean Diabetes Association.

  16. Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance.

    PubMed

    Gaggini, Melania; Carli, Fabrizia; Rosso, Chiara; Buzzigoli, Emma; Marietti, Milena; Della Latta, Veronica; Ciociaro, Demetrio; Abate, Maria Lorena; Gambino, Roberto; Cassader, Maurizio; Bugianesi, Elisabetta; Gastaldelli, Amalia

    2018-01-01

    Plasma concentrations of amino acids (AAs), in particular, branched chain AAs (BCAAs), are often found increased in nonalcoholic fatty liver disease (NAFLD); however, if this is due to increased muscular protein catabolism, obesity, and/or increased insulin resistance (IR) or impaired tissue metabolism is unknown. Thus, we evaluated a) if subjects with NAFLD without obesity (NAFLD-NO) compared to those with obesity (NAFLD-Ob) display altered plasma AAs compared to controls (CTs); and b) if AA concentrations are associated with IR and liver histology. Glutamic acid, serine, and glycine concentrations are known to be altered in NAFLD. Because these AAs are involved in glutathione synthesis, we hypothesized they might be related to the severity of NAFLD. We therefore measured the AA profile of 44 subjects with NAFLD without diabetes and who had a liver biopsy (29 NAFLD-NO and 15 NAFLD-Ob) and 20 CTs without obesity, by gas chromatography-mass spectrometry, homeostasis model assessment of insulin resistance, hepatic IR (Hep-IR; Hep-IR = endogenous glucose production × insulin), and the new glutamate-serine-glycine (GSG) index (glutamate/[serine + glycine]) and tested for an association with liver histology. Most AAs were increased only in NAFLD-Ob subjects. Only alanine, glutamate, isoleucine, and valine, but not leucine, were increased in NAFLD-NO subjects compared to CTs. Glutamate, tyrosine, and the GSG-index were correlated with Hep-IR. The GSG-index correlated with liver enzymes, in particular, gamma-glutamyltransferase (R = 0.70), independent of body mass index. Ballooning and/or inflammation at liver biopsy were associated with increased plasma BCAAs and aromatic AAs and were mildly associated with the GSG-index, while only the new GSG-index was able to discriminate fibrosis F3-4 from F0-2 in this cohort. Increased plasma AA concentrations were observed mainly in subjects with obesity and NAFLD, likely as a consequence of increased IR and protein catabolism

  17. Relationships between metabolic profile, hypertension and uric acid with cardiometabolic risk in adolescents with abdominal obesity: impact of geodemographic factors on the prevalence of abdominal obesity.

    PubMed

    Bouhenni, Hamida; Daoudi, Hadjer; Djemai, Haidar; Noirez, Philippe; Rouabah, Abdelkader; Vitiello, Damien; Rouabah, Leila

    2017-11-23

    Background Association of hyperuricemia, dyslipidemia and high blood pressure (BP) among adolescents with high waist-to-height ratio (WHtR) remains not fully addressed and could represent a new way to diagnose adolescents early with cardiometabolic risk. Objective We aimed to determine abdominal obesity (AO) prevalence and investigate relations between AO, uric acid (UA), lipid profiles, BP and geographical patterns in adolescents. Subjects 577 and 204 Algerian students aged between 10 and 19 years were included in our epidemiological and biochemical studies, respectively. Methods Height, weight, waist circumference (Wc) and hip circumferences, body mass index (BMI) and BP were measured. Fasting blood sampling was performed to measure glycemia, lipid profile, uricemia, insulinemia and leptinemia. The WHtR ≥0.50 was applied for the diagnosis of AO and geodemographics was evaluated. Results The prevalence of AO was 12.13% among all students, 19.17% and 16.39% among students living in urban and plain areas, respectively. The risk of AO may be reduced in rural and mountainous areas. Lipid parameters, UA, insulin and leptin serum concentrations were significantly increased in adolescents with WHtR ≥0.50 compared to those with WHtR <0.50. Cardiometabolic risk was increased with WHtR ≥0.50 and BMI >26. Means of BMI, Wc, BP, and lipid parameters were significantly increased in the fourth quartiles compared to the first quartile of UA. Conclusion Urban areas and plains represent factors contributing to AO and WHtR ≥0.50 may be used as a cut-off point to define risks of high BP, lipid abnormalities and UA serum level in Algerian adolescents.

  18. Body fat distribution modulates insulin sensitivity in post-menopausal overweight and obese women: a MONET study.

    PubMed

    Tousignant, B; Faraj, M; Conus, F; Garrel, D; Brochu, M; Rabasa-Lhoret, R; Coderre, L

    2008-11-01

    Central fat mass (CFM) correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications. On the other hand, increased peripheral fat mass (PFM) is associated with higher insulin sensitivity. Thus, we examined the contribution of adipose tissue distribution, as assessed by the PFM/CFM ratio, to insulin sensitivity in overweight and obese postmenopausal women. A total of 124 nondiabetic overweight and obese postmenopausal women underwent an oral glucose tolerance test (OGTT) and a hyperinsulinemic/euglycemic (HI) clamp. Body composition was determined using computed tomography for visceral adipose tissue (VAT) and dual X-ray absorptiometry for fat mass, lean body mass and their respective proportions. Participants were divided by tertiles of the PFM/CFM ratio. Participants with preferential CFM (group 1) had higher fasting insulin levels and insulin area under the curve (AUC) during OGTT, as well as lower glucose infusion rates during the HI clamp, whether it was expressed per kg of body weight (M) or per kg of fat-free mass (Mm), compared with the other two groups. The PFM/CFM ratio also correlated significantly with fasting insulin (r=-0.32, P<0.001), the insulin AUC (r=-0.42 P<0.001), M (r=0.39 P<0.001) and Mm (r=0.37 P<0.001). Using hierarchical regression, we demonstrated that the PFM/CFM ratio was an independent predictor of insulin AUC, M and Mm and that its sequential addition to CFM and VAT improved significantly the predictive value of the model for insulin sensitivity for all variables except fasting insulin. The PFM/CFM ratio, which integrates the antagonistic effects of both central and peripheral depots on insulin sensitivity, added substantially to the prediction of insulin sensitivity over VAT and CFM alone.

  19. Modulation of leptin, insulin, and growth hormone in obese pony mares under chronic nutritional restriction and supplementation with ractopamine hydrochloride.

    PubMed

    Buff, Preston R; Johnson, Philip J; Wiedmeyer, Charles E; Ganjam, Venkataseshu K; Messer Iv, Nat T; Keisler, Duane H

    2006-01-01

    Horses fed beyond their nutritional requirement and that are physically inactive will develop obesity, which is often accompanied by insulin resistance and heightened risk of laminitis. The use of pharmacologic agents in combination with nutritional restriction may promote weight loss in obese horses unable to exercise because of laminitic pain. This study shows that reducing feed intake of brome grass hay to 75% of ad libitum intake in obese pony mares reduces body weight without induced exercise. Additional supplementation of ractopamine hydrochloride for 6 weeks resulted in a tendency for increased weight loss. Subsequent modulation of obesity-associated hormones, leptin and insulin, as a result of caloric restriction was observed.

  20. A nude mouse model of obesity to study the mechanisms of resistance to aromatase inhibitors.

    PubMed

    Schech, Amanda; Yu, Stephen; Goloubeva, Olga; McLenithan, John; Sabnis, Gauri

    2015-08-01

    Obesity is a risk factor for breast cancer progression. Breast cancer patients who are overweight or obese or have excess abdominal fat have an increased risk of local or distant recurrence and cancer-related death. Hormone depletion therapies can also cause weight gain, exacerbating the risk for these patients. To understand the effect of obesity on hormone-dependent human breast cancer tumors, we fed ovariectomized athymic nude mice a diet containing 45% kcal fat and 17% kcal sucrose (high fat sucrose diet (HFSD)), 10% kcal fat (low fat diet (LFD)), or a standard chow diet (chow). The mice fed the HFSD developed metabolic abnormalities consistent with the development of obesity such as weight gain, high fasting blood glucose, and impaired glucose tolerance. These mice also developed hyperinsulinemia and insulin resistance. The obese mice also had a higher tumor growth rate compared to the lean mice. Furthermore, the obese mice showed a significantly reduced responsiveness to letrozole. To understand the role of obesity in this reduced responsiveness, we examined the effect of insulin on the growth of MCF-7Ca cells in response to estrogen or letrozole. The presence of insulin rendered MCF-7Ca cells less responsive to estrogen and letrozole. Exogenous insulin treatment of MCF-7Ca cells also resulted in increased p-Akt as well as ligand-independent phosphorylation of ERα. These findings suggest that diet-induced obesity may result in reduced responsiveness of tumors to letrozole due to the development of hyperinsulinemia. We conclude that obesity influences the response and resistance of breast cancer tumors to aromatase inhibitor treatment. © 2015 Society for Endocrinology.