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Sample records for age obesity diabetes

  1. Obesity and diabetes.

    PubMed

    Riobó Serván, Pilar

    2013-09-01

    Type 2 diabetes mellitus is characterized by hyperglycemia, insulin resistance, and relative impairment in insulin secretion and its possible long term complications. Its pathogenesis is poorly understood, but both genetic and environmental factors, such as obesity and aging, play a key role. "Diabesity" is a new term which refers to diabetes occurring in the context of obesity. In this article, we will discuss the epidemiology and impact of diabetes and obesity and will also outline the components of the metabolic syndrome and the studies that demonstrate that screening and prevention are possible in an attempt to control this epidemic.

  2. Duration of Abdominal Obesity Beginning in Young Adulthood and Incident Diabetes Through Middle Age

    PubMed Central

    Reis, Jared P.; Hankinson, Arlene L.; Loria, Catherine M.; Lewis, Cora E.; Powell-Wiley, Tiffany; Wei, Gina S.; Liu, Kiang

    2013-01-01

    OBJECTIVE To examine whether the duration of abdominal obesity determined prospectively using measured waist circumference (WC) is associated with the development of new-onset diabetes independent of the degree of abdominal adiposity. RESEARCH DESIGN AND METHODS The Coronary Artery Risk Development in Young Adults Study is a multicenter, community-based, longitudinal cohort study of 5,115 white and black adults aged 18–30 years in 1985 to 1986. Years spent abdominally obese were calculated for participants without abdominal obesity (WC >102 cm in men and >88 cm in women) or diabetes at baseline (n = 4,092) and was based upon repeat measurements conducted 2, 5, 7, 10, 15, 20, and 25 years later. RESULTS Over 25 years, 392 participants developed incident diabetes. Overall, following adjustment for demographics, family history of diabetes, study center, and time varying WC, energy intake, physical activity, smoking, and alcohol, each additional year of abdominal obesity was associated with a 4% higher risk of developing diabetes [hazard ratio (HR) 1.04 (95% CI 1.02–1.07)]. However, a quadratic model best represented the data. HRs for 0, 1–5, 6–10, 11–15, 16–20, and >20 years of abdominal obesity were 1.00 (referent), 2.06 (1.43–2.98), 3.45 (2.28–5.22), 3.43 (2.28–5.22), 2.80 (1.73–4.54), and 2.91 (1.60–5.29), respectively; P-quadratic < 0.001. CONCLUSIONS Longer duration of abdominal obesity was associated with substantially higher risk for diabetes independent of the degree of abdominal adiposity. Preventing or at least delaying the onset of abdominal obesity in young adulthood may lower the risk of developing diabetes through middle age. PMID:23248193

  3. Prevention of Obesity and Type 2 Diabetes with Aged Citrus Peel (Chenpi) Extract.

    PubMed

    Guo, Jingjing; Tao, Hanlin; Cao, Yong; Ho, Chi-Tang; Jin, Shengkang; Huang, Qingrong

    2016-03-16

    Chenpi is the dry peel of the plant Citrus reticulata Blanco after an aging processing. It has been used as an antidigestive and anti-inflammatory traditional medicine, as well as culinary seasoning and dietary supplement, in China. However, its efficacy and underlying scientific mechanism have not been sufficiently investigated. Chenpi is uniquely enriched with a high content of 5-demethylated polymethoxyflavones (5-OH PMFs). The effect of chenpi extract on improving metabolic features was examined using high-fat diet (HFD)-induced obesity/diabetes mouse model. Oral administration of 0.25 and 0.5% chenpi extract in food over 15 weeks markedly prevented HFD-induced obesity, hepatic steatosis, and diabetic symptoms. The beneficial effect is associated with 5'-adenosine monophosphate-activated protein kinase (AMPK) activation in adipose tissue. Our results indicate that 5-OH PMFs-enriched chenpi extract is effective in preventing obesity and type 2 diabetes, and its effect might be related to improvement in lipid metabolism associated with activation of the AMPK pathway. PMID:26912037

  4. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    PubMed Central

    Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs. PMID:26337083

  5. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

    PubMed

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M; Mahmoudi, Morteza; De Rooij, Felix W M; Sijbrands, Eric; Peppelenbosch, Maikel P; Rezaee, Farhad

    2015-10-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.

  6. Biphasic Decline of β-Cell Function with Age in Euglycemic Non-Obese Diabetic (NOD) Mice Parallels Diabetes Onset

    PubMed Central

    Cechin, Sirlene R.; Lopez-Ocejo, Omar; Karpinsky-Semper, Darla; Buchwald, Peter

    2015-01-01

    A gradual decline in insulin response is known to precede the onset of type 1 diabetes (T1D). To track age-related changes in the β-cell function of non-obese diabetic (NOD) mice, the most commonly used animal model for T1D, and to establish differences between those who do and do not become hyperglycemic, we performed a long-term longitudinal oral glucose tolerance test (OGTT) study (10–42 weeks) in combination with immunofluorescence imaging of islet morphology and cell proliferation. We observed a clear biphasic decline in insulin secretion (AUC0–30min) even in euglycemic animals. A first phase (10–28 weeks) consisted of a relatively rapid decline and paralleled diabetes development in the same cohort of animals. This was followed by a second phase (29–42 weeks) during which insulin secretion declined much slower while no additional animals became diabetic. Blood glucose profiles showed a corresponding, but less pronounced change: the area under the concentration curve (AUC0–150min) increased with age, and fit with a bilinear model indicated a rate-change in the trendline around 28 weeks. In control NOD scids, no such changes were observed. Islet morphology also changed with age as islets become surrounded by mononuclear infiltrates, and, in all mice, islets with immune cell infiltration around them showed increased β-cell proliferation. In conclusion, insulin secretion declines in a biphasic manner in all NOD mice. This trend, as well as increased β-cell proliferation, is present even in the NODs that never become diabetic, whereas, it is absent in control NOD scid mice. PMID:26099053

  7. Proteome-wide alterations on adipose tissue from obese patients as age-, diabetes- and gender-specific hallmarks

    PubMed Central

    Gómez-Serrano, María; Camafeita, Emilio; García-Santos, Eva; López, Juan A.; Rubio, Miguel A.; Sánchez-Pernaute, Andrés; Torres, Antonio; Vázquez, Jesús; Peral, Belén

    2016-01-01

    Obesity is a main global health issue and an outstanding cause of morbidity and mortality predisposing to type 2 diabetes (T2DM) and cardiovascular diseases. Huge research efforts focused on gene expression, cellular signalling and metabolism in obesity have improved our understanding of these disorders; nevertheless, to bridge the gap between the regulation of gene expression and changes in signalling/metabolism, protein levels must be assessed. We have extensively analysed visceral adipose tissue from age-, T2DM- and gender-matched obese patients using high-throughput proteomics and systems biology methods to identify new biomarkers for the onset of T2DM in obesity, as well as to gain insight into the influence of aging and gender in these disorders. About 250 proteins showed significant abundance differences in the age, T2DM and gender comparisons. In diabetic patients, remarkable gender-specific hallmarks were discovered regarding redox status, immune response and adipose tissue accumulation. Both aging and T2DM processes were associated with mitochondrial remodelling, albeit through well-differentiated proteome changes. Systems biology analysis highlighted mitochondrial proteins that could play a key role in the age-dependent pathophysiology of T2DM. Our findings could serve as a framework for future research in Translational Medicine directed at improving the quality of life of obese patients. PMID:27160966

  8. Proteome-wide alterations on adipose tissue from obese patients as age-, diabetes- and gender-specific hallmarks.

    PubMed

    Gómez-Serrano, María; Camafeita, Emilio; García-Santos, Eva; López, Juan A; Rubio, Miguel A; Sánchez-Pernaute, Andrés; Torres, Antonio; Vázquez, Jesús; Peral, Belén

    2016-01-01

    Obesity is a main global health issue and an outstanding cause of morbidity and mortality predisposing to type 2 diabetes (T2DM) and cardiovascular diseases. Huge research efforts focused on gene expression, cellular signalling and metabolism in obesity have improved our understanding of these disorders; nevertheless, to bridge the gap between the regulation of gene expression and changes in signalling/metabolism, protein levels must be assessed. We have extensively analysed visceral adipose tissue from age-, T2DM- and gender-matched obese patients using high-throughput proteomics and systems biology methods to identify new biomarkers for the onset of T2DM in obesity, as well as to gain insight into the influence of aging and gender in these disorders. About 250 proteins showed significant abundance differences in the age, T2DM and gender comparisons. In diabetic patients, remarkable gender-specific hallmarks were discovered regarding redox status, immune response and adipose tissue accumulation. Both aging and T2DM processes were associated with mitochondrial remodelling, albeit through well-differentiated proteome changes. Systems biology analysis highlighted mitochondrial proteins that could play a key role in the age-dependent pathophysiology of T2DM. Our findings could serve as a framework for future research in Translational Medicine directed at improving the quality of life of obese patients. PMID:27160966

  9. Obesity and diabetes in an aging population: time to rethink definitions and management?

    PubMed

    Rothberg, Amy E; Halter, Jeffrey B

    2015-02-01

    Regardless of pathophysiology and diagnostic criteria, the population of older adults with diabetes is highly heterogeneous. As adults with type 2 diabetes age and develop multiple comorbid health conditions, they may experience many challenges to good diabetes care and self-management. Age of diagnosis and duration of diabetes largely determine the likelihood for comorbidity. Treating such a diverse elderly population may result in inadequate glycemic control either because of overtreatment, leading to hypoglycemia, or because of other complications and preexisting comorbidities. It is imperative that treatment decisions are based on patient preferences, unique and likely evolving health status, and longevity.

  10. Obesity and diabetes genes are associated with being born small for gestational age: Results from the Auckland Birthweight Collaborative study

    PubMed Central

    2010-01-01

    Background Individuals born small for gestational age (SGA) are at increased risk of rapid postnatal weight gain, later obesity and diseases in adulthood such as type 2 diabetes, hypertension and cardiovascular diseases. Environmental risk factors for SGA are well established and include smoking, low pregnancy weight, maternal short stature, maternal diet, ethnic origin of mother and hypertension. However, in a large proportion of SGA, no underlying cause is evident, and these individuals may have a larger genetic contribution. Methods In this study we tested the association between SGA and polymorphisms in genes that have previously been associated with obesity and/or diabetes. We undertook analysis of 54 single nucleotide polymorphisms (SNPs) in 546 samples from the Auckland Birthweight Collaborative (ABC) study. 227 children were born small for gestational age (SGA) and 319 were appropriate for gestational age (AGA). Results and Conclusion The results demonstrated that genetic variation in KCNJ11, BDNF, PFKP, PTER and SEC16B were associated with SGA and support the concept that genetic factors associated with obesity and/or type 2 diabetes are more prevalent in those born SGA compared to those born AGA. We have previously determined that environmental factors are associated with differences in birthweight in the ABC study and now we have demonstrated a significant genetic contribution, suggesting that the interaction between genetics and the environment are important. PMID:20712903

  11. Treating the obese diabetic.

    PubMed

    Kenkre, Julia; Tan, Tricia; Bloom, Stephen

    2013-03-01

    Type 2 diabetes and obesity are intimately linked; reduction of bodyweight improves glycemic control, mortality and morbidity. Treating obesity in the diabetic is hampered as some diabetic treatments lead to weight gain. Bariatric surgery is currently the most effective antiobesity treatment and causes long-term remission of diabetes in many patients. However, surgery has a high cost and is associated with a significant risk of complications, and in practical terms only limited numbers can undergo this therapy. The choice of pharmacological agents suitable for treatment of diabetes and obesity is currently limited. The glucagon-like peptide-1 receptor agonists improve glycemia and induce a modest weight loss, but there are doubts over their long-term safety. New drugs such as lorcaserin and phentermine/topiramate are being approved for obesity and have modest, salutary effects on glycemia, but again long-term safety is unclear. This article will also examine some future avenues for development, including gut hormone analogues that promise to combine powerful weight reduction with beneficial effects on glucose metabolism. PMID:23473594

  12. Obesity and Life Expectancy with and without Diabetes in Adults Aged 55 Years and Older in the Netherlands: A Prospective Cohort Study

    PubMed Central

    Ligthart, Symen; Peeters, Anna; Hofman, Albert; Nusselder, Wilma; Franco, Oscar H.

    2016-01-01

    Background Overweight and obesity are associated with increased risk of type 2 diabetes. Limited evidence exists regarding the effect of excess weight on years lived with and without diabetes. We aimed to determine the association of overweight and obesity with the number of years lived with and without diabetes in a middle-aged and elderly population. Methods and Findings The study included 6,499 individuals (3,656 women) aged 55 y and older from the population-based Rotterdam Study. We developed a multistate life table to calculate life expectancy for individuals who were normal weight, overweight, and obese and the difference in years lived with and without diabetes. For life table calculations, we used prevalence, incidence rate, and hazard ratios (HRs) for three transitions (healthy to diabetes, healthy to death, and diabetes to death), stratifying by body mass index (BMI) at baseline and adjusting for confounders. During a median follow-up of 11.1 y, we observed 697 incident diabetes events and 2,192 overall deaths. Obesity was associated with an increased risk of developing diabetes (HR: 2.13 [p < 0.001] for men and 3.54 [p < 0.001] for women). Overweight and obesity were not associated with mortality in men and women with or without diabetes. Total life expectancy remained unaffected by overweight and obesity. Nevertheless, men with obesity aged 55 y and older lived 2.8 (95% CI −6.1 to −0.1) fewer y without diabetes than normal weight individuals, whereas, for women, the difference between obese and normal weight counterparts was 4.7 (95% CI −9.0 to −0.6) y. Men and women with obesity lived 2.8 (95% CI 0.6 to 6.2) and 5.3 (95% CI 1.6 to 9.3) y longer with diabetes, respectively, compared to their normal weight counterparts. Since the implications of these findings could be limited to middle-aged and older white European populations, our results need confirmation in other populations. Conclusions Obesity in the middle aged and elderly is associated

  13. Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β-Cell Mass in Middle-Aged Obese Diabetic Mice

    PubMed Central

    Alkhalidy, Hana; Moore, William; Zhang, Yanling; Wang, Aihua; Ali, Mostafa; Suh, Kyung-Shin; Zhen, Wei; Cheng, Zhiyong; Jia, Zhenquan; Hulver, Matthew

    2015-01-01

    Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction. PMID:26064984

  14. Beyond Diabetes: Does Obesity-Induced Oxidative Stress Drive the Aging Process?

    PubMed Central

    Salmon, Adam B.

    2016-01-01

    Despite numerous correlative data, a causative role for oxidative stress in mammalian longevity has remained elusive. However, there is strong evidence that increased oxidative stress is associated with exacerbation of many diseases and pathologies that are also strongly related to advanced age. Obesity, or increased fat accumulation, is one of the most common chronic conditions worldwide and is associated with not only metabolic dysfunction but also increased levels of oxidative stress in vivo. Moreover, obesity is also associated with significantly increased risks of cardiovascular disease, neurological decline and cancer among many other diseases as well as a significantly increased risk of mortality. In this review, we investigate the possible interpretation that the increased incidence of these diseases in obesity may be due to chronic oxidative stress mediating segmental acceleration of the aging process. Understanding how obesity can alter cellular physiology beyond that directly related to metabolic function could open new therapeutic areas of approach to extend the period of healthy aging among people of all body composition. PMID:27438860

  15. From obesity to diabetes.

    PubMed

    Keller, U

    2006-07-01

    The prevalence of obesity has been increasing dramatically in the last decades in the whole world, not only in industrialized countries but also in developing areas. A major complication of obesity is insulin resistance and type 2 diabetes. Diabetes is also rapidly increasing world-wide--reaching a prevalence in adults of approx. 5-6% in Central Europe and in the US, and more than 50% in specific, genetically prone populations. This article reviews pathogenetic mechanisms linking obesity and type 2 diabetes. Emphasis is placed on the observation that excessive amounts of adipocytes are associated with an impairment of insulin sensitivity, a key feature of the "metabolic syndrome". This is a cluster of metabolic abnormalities such as type 2 diabetes, hypertension and dyslipidemia; all of them are enhanced by the presence of visceral (abdominal) obesity and all contribute to the increased cardiovascular risk observed in these patients. Besides release of free fatty acids, adipocytes secrete substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-alpha and interleukin 6. Increased turnover of free fatty acids interferes with intracellular metabolism of glucose in the muscle, and they exert lipotoxic effect on pancreatic beta-cells. The pre-receptor metabolism of cortisol is enhanced in visceral adipose tissue by activation of 11 beta-hydroxysteroid dehydrogenase type 1. A new class of anti-diabetic drugs (thiazolidinediones, or glitazones) bind to peroxisome proliferator activated receptor (PPAR-gamma) and lower thereby plasma free fatty acids and cytokine production in adipocytes, in addition to a decrease of resistin and an increase in adiponectin observed in animals, resulting in an overall increase in insulin sensitivity and in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance and prevent the development of diabetes should be a reduction in body weight in overweight subjects, and an

  16. Diabetes and obesity in pregnancy.

    PubMed

    Simmons, David

    2011-02-01

    An epidemic of obesity is affecting growing numbers of women in their childbearing years increasing their risk of obstetric complications including diabetes, hypertension, pre-eclampsia, some malformations, macrosomia and the need for obstetric intervention. There is growing evidence that maternal obesity may increase the risk of obesity and diabetes in the offspring. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require management during pregnancy. Management of obesity including weight loss and physical activity prior to pregnancy is likely to be beneficial for mother and baby, although the benefits of bariatric surgery remain unclear at this time. Limiting gestational weight gain to 5-9 kg among pregnant obese women is likely to improve obstetric outcomes, but how to achieve this remains an active area of research. If gestational diabetes develops, there is good evidence that clinical management reduces the risk of adverse pregnancy outcomes.

  17. Pediatric obesity & type 2 diabetes.

    PubMed

    Dea, Tara L

    2011-01-01

    This article focuses on (a) identifying obesity and other risk factors for developing type 2 diabetes, (b) differentiating between pediatric type 1 diabetes and type 2 diabetes, and (c) treating pediatric type 2 diabetes. Obesity has significant implications on a child's health, including an increased risk for insulin resistance and progression to type 2 diabetes. Type 2 diabetes in children, characterized by insulin resistance and relative pancreatic b-cell failure due to the increased demand for insulin production, has now reached epidemic proportions. Longitudinal research on pediatric type 2 diabetes, however, is lacking because this epidemic is relatively new. Treatment of type 2 diabetes in children is focused on lifestyle modification with weight management/increased physical activity, and pharmacological management through oral medication or insulin therapy. Because children with type 2 diabetes are at risk for developing diabetes-related complications earlier in life, they need to be closely monitored for comorbidities.

  18. Vitamin D deficiency is a risk factor for obesity and diabetes type 2 in women at late reproductive age.

    PubMed

    Grineva, E N; Karonova, T; Micheeva, E; Belyaeva, O; Nikitina, I L

    2013-07-01

    It was suggested that glucose metabolism and body fat content depend on serum levels of 25-hydroxyvitamin D [25(OH)D]. We studied 320 healthy women at late reproductive age of 40 to 52 years old (mean age 46.1±4.5) from St. Petersburg (North-West region of Russia). 25(ОН)D levels were from 19.4 to 134.0 nMol/L (mean 52.9±22.7). Vitamin D deficiency (lower than 50 nMol/L) and insufficiency (50-75 nMol/L) was revealed in 59.1% and 27.8% of women, respectively. The study showed that low 25(OH)D levels were associated with obesity (r=-0.35, p$#X003C0.01), increased plasma glucose levels after OGTT (r=-0.31, p$#X003C0.01) and decreased insulin sensitivity index (r=-0.28, p$#X003C0.01). We found that 25(OH)D levels below 50 nMol/L were associated with obesity risk (OR 2.25[1.05-3.95], CI 95%) but not with risk of impaired glucose metabolism (1.07[0.54-2.12],CI95%). Our results showed that vitamin D insufficiency is highly prevalent in the population of healthy women. Low 25(OH)D levels correlated with high body fat, glucose levels and decreased insulin sensitivity. We conclude that vitamin D deficiency is a potential risk factor for obesity and development of insulin resistance leading to diabetes type 2.

  19. Vitamin D deficiency is a risk factor for obesity and diabetes type 2 in women at late reproductive age

    PubMed Central

    Grineva, EN; Karonova, T; Micheeva, E; Belyaeva, O; Nikitina, IL

    2013-01-01

    It was suggested that glucose metabolism and body fat content depend on serum levels of 25-hydroxyvitamin D [25(OH)D]. We studied 320 healthy women at late reproductive age of 40 to 52 years old (mean age 46.1±4.5) from St. Petersburg (North-West region of Russia). 25(OH)D levels were from 19.4 to 134.0 nMol/L (mean 52.9±22.7). Vitamin D deficiency (lower than 50 nMol/L) and insufficiency (50-75 nMol/L) was revealed in 59.1% and 27.8% of women, respectively. The study showed that low 25(OH)D levels were associated with obesity (r=-0.35, p<0.01), increased plasma glucose levels after OGTT (r=-0.31, p<0.01) and decreased insulin sensitivity index (r=-0.28, p<0.01). We found that 25(OH)D levels below 50 nMol/L were associated with obesity risk (OR 2.25[1.05-3.95], CI 95%) but not with risk of impaired glucose metabolism (1.07[0.54-2.12],CI95%). Our results showed that vitamin D insufficiency is highly prevalent in the population of healthy women. Low 25(OH)D levels correlated with high body fat, glucose levels and decreased insulin sensitivity. We conclude that vitamin D deficiency is a potential risk factor for obesity and development of insulin resistance leading to diabetes type 2. PMID:23924693

  20. Visceral obesity and diabetes.

    PubMed

    Björntorp, P; Rosmond, R

    1999-01-01

    Visceral obesity is a strong predictor of type 2 (non-insulin-dependent) diabetes and is associated with insulin resistance. In addition, research has indicated that the accumulation of visceral fat is regulated by endocrine mechanisms. Data suggest that progressive malfunction of the hypothalamic-pituitary-adrenal (HPA) axis, with elevation of levels of cortisol and reductions in levels of sex steroids and growth hormone, is associated with visceral accumulation of fat that contributes to circulating levels of free fatty acids, and that these factors are implicated in the development of insulin resistance. Furthermore, failure of central feedback control of the HPA axis by glucocorticoid receptors (GR) appears to be correlated with polymorphisms near the first exons of the GR gene. The HPA axis disturbances are similar to those seen after prolonged exposure to environmental stress. Psychosocial and socioeconomic factors, alcohol, depressive traits and anxiety are linked to HPA axis abnormalities.

  1. Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring Neurodevelopment at 6 and 18 Months of Age – A Follow Up from the PREOBE Cohort

    PubMed Central

    Torres-Espinola, Francisco J.; Berglund, Staffan K; García-Valdés, Luz Mª; Segura, Mª Teresa; Jerez, Antonio; Campos, Daniel; Moreno-Torres, Rosario; Rueda, Ricardo; Catena, Andrés; Pérez-García, Miguel; Campoy, Cristina

    2015-01-01

    Background Brain development in fetal life and early infancy is critical to determine lifelong performance in various neuropsychological domains. Metabolic pathologies such as overweight, obesity, and gestational diabetes in pregnant women are prevalent and increasing risk factors that may adversely affect long-term brain development in their offspring. Objective The objective of this research was to investigate the influence of maternal metabolic pathologies on the neurodevelopment of the offspring at 6 and 18 months of life. Design This was a prospective case-control study of 331 mother- and child pairs from Granada, Spain. The mothers were included during pregnancy into four groups according to their pre-gestational body mass index and their gestational diabetes status; overweight (n:56), obese (n:64), gestational diabetic (n:79), and healthy normal weight controls (n:132). At 6 months and 18 months we assessed the children with the Bayley III scales of neurodevelopment. Results At 6 months (n=215), we found significant group differences in cognition composite language, and expressive language. Post hoc test revealed unexpectedly higher scores in the obese group compared to the normal weight group and a similar trend in overweight and diabetic group. The effects on language remained significant after adjusting for confounders with an adjusted odds ratio for a value above median in composite language score of 3.3 (95% CI: 1.1, 10.0; p=0.035) for children of obese mothers. At 18 month (n=197), the offspring born to obese mothers had lost five points in language composite scores and the previous differences in language and cognition was replaced by a suggestive trend of lower gross motor scores in the overweight, obese, and diabetic groups. Conclusions Infants of obese mothers had a temporary accelerated development of cognition and language, followed by a rapid deceleration until 18 months of age, particularly of language scores. This novel observation prompts

  2. Diabetes, Obesity, and the Brain: New Developments in Biobehavioral Medicine.

    PubMed

    Everson-Rose, Susan A; Ryan, John P

    2015-01-01

    Diabetes and obesity, two major public health concerns, are associated with increased risk for problems in multiple organ systems, including the central nervous system. The adverse effects of diabetes and obesity on cognitive functioning are increasingly well recognized. This special issue of Psychosomatic Medicine features the latest research linking diabetes, obesity, and brain structure, function, and metabolism and follows a special meeting on this topic organized by the American Psychosomatic Society in October 2013. Evidence for the increased prevalence of diabetes and obesity is reviewed as it relates to cognitive decline. These articles indicate that the age of onset of Type 1 diabetes may be relevant to future cognitive function and that disease duration of Type 2 diabetes and sociocultural factors are related to cognitive decline during the aging process. The hypothalamus and other neural circuits, notably the dopaminergic system that underlies feeding and reward-related aspects of food intake, are among the key factors involved in obesity. Research on the associations between obesity and cognitive function is described using the positive effects of weight reduction following bariatric surgery or behavioral methods. This special issue concludes with a conceptual framework for linking obesity and diabetes with accelerated cognitive decline as related to the aging process. The collection of articles highlights the importance of using a life span perspective to understand the influence of both Type 1 and Type 2 diabetes on brain metabolism, function, and structure. Moreover, these studies show that distressing environmental circumstances can adversely influence neurocognitive dysfunction associated with obesity and diabetes.

  3. Optimal Pharmacologic Treatment Strategies in Obesity and Type 2 Diabetes

    PubMed Central

    Goswami, Gayotri; Shinkazh, Nataliya; Davis, Nichola

    2014-01-01

    The prevalence of obesity has increased to pandemic levels worldwide and is related to increased risk of morbidity and mortality. Metabolic comorbidities are commonly associated with obesity and include metabolic syndrome, pre-diabetes, and type 2 diabetes. Even if the prevalence of obesity remains stable until 2030, the anticipated numbers of people with diabetes will more than double as a consequence of population aging and urbanization. Weight reduction is integral in the prevention of diabetes among obese adults with pre-diabetes. Lifestyle intervention and weight reduction are also key in the management of type 2 diabetes. Weight loss is challenging for most obese patients, but for those with diabetes, it can pose an even greater challenge due to the weight gain associated with many treatment regimens. This article will review optimal treatment strategies for patients with comorbid obesity and type 2 diabetes. The role of anti-obesity agents in diabetes will also be reviewed. This literature review will provide readers with current strategies for the pharmacologic treatment of obesity and diabetes with a focus on the weight outcomes related to diabetes treatments. PMID:26237392

  4. [Obesity and type 2 diabetes].

    PubMed

    Toplak, Hermann; Hoppichler, Friedrich; Wascher, Thomas C; Schindler, Karin; Ludvik, Bernhard

    2016-04-01

    Obesity and Type 2 Diabetes are nowadays summarized as "diabesity". That is due to the fact that obesity is frequently preceding and the most important risk factor in the increase of Type 2 Diabetes. The body mass index (BMI) is a crude measure of body fatness. Even normal weight persons can have lack in muscles (sarcopenia), which leads to the recommendation to measure waist und body fatness (e.g. BIA). Lifestyle management including nutrition and physical activity are important for diabetes prevention. In the therapy of Type 2 Diabetes body weight is increasingly used as secondary target. Also the choice of the anti-diabetic medication and concomitant medications is increasingly influenced by body weight. The significance of anti-obesity medications in the therapy of type 2 diabetes will have to be clarified by future studies. Bariatric surgery is at present indicated with a BMI above BMI > 35 kg/m(2) and can lead at least to partial diabetes remission but has to be part of a lifelong care concept. PMID:27052246

  5. Age-related consequences of childhood obesity.

    PubMed

    Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

    2014-01-01

    The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood. PMID:24434909

  6. Age-related consequences of childhood obesity.

    PubMed

    Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

    2014-01-01

    The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood.

  7. Evolution from obesity to diabetes.

    PubMed

    Golay, A; Felber, J P

    1994-01-01

    The relationship between obesity and Type 2 diabetes mellitus is so closely related that it is worth questioning the possibility of obesity being more than just one diabetes risk factor among others but a factor which participates causally to the development of Type 2 Diabetes on a genetic background. In this review, the evolution of normal glucose tolerance towards impaired glucose tolerance corresponds to the development of compensatory metabolic changes. These compensatory mechanisms are hyperinsulinaemia and postprandial hyperglycaemia which prevents a defect in glucose uptake and especially glucose storage. These compensatory responses are overcome with time and diabetes develops in spite of the hyperinsulinaemia and the hyperglycaemia. The capacity for glucose storage is decreased and cannot be overcome at this stage by increases of both glucose and insulinemic responses. Inhibition of glycogen synthase activity by an increased muscle glycogen concentration is probably more powerful than its stimulation by insulin and glucose and the capacity for glucose storage remains decreased. Finally with time insulin secretion gradually decreases as a consequence of chronic hyperglycaemia and results in full pancreatic decompensation. At this stage hepatic glucose production is increased. The most important factor in the evolution from obesity to diabetes reside in the permanence of the increase in lipid oxidation and mainly in the duration of obesity. An important consequence of permanently high lipid oxidation is the chronic resistance to glucose uptake, initially compensated for by increased plasma insulin and glucose concentrations. A vicious circle starts after insulin resistance to glucose uptake appears, followed by hyperglycaemia blocking the glucose storage system and by the lack of storing capacity leading to a rise in glycaemia. In conclusion, all these metabolic phenomena are appearing in a sequential way, progressively adapting to the deteriorating

  8. Obesity- and aging-induced excess of central transforming growth factor-β potentiates diabetic development via an RNA stress response.

    PubMed

    Yan, Jingqi; Zhang, Hai; Yin, Ye; Li, Juxue; Tang, Yizhe; Purkayastha, Sudarshana; Li, Lianxi; Cai, Dongsheng

    2014-09-01

    The brain, in particular the hypothalamus, plays a role in regulating glucose homeostasis; however, it remains unclear whether this organ is causally and etiologically involved in the development of diabetes. Here, we found that hypothalamic transforming growth factor-β (TGF-β) production is excessive under conditions of not only obesity but also aging, which are two general etiological factors of type 2 diabetes. Pharmacological and genetic approaches revealed that central TGF-β excess caused hyperglycemia and glucose intolerance independent of a change in body weight. Further, using cell-specific genetic analyses in vivo, we found that astrocytes and proopiomelanocortin neurons are responsible for the production and prodiabetic effect of central TGF-β, respectively. Mechanistically, TGF-β excess induced a hypothalamic RNA stress response, resulting in accelerated mRNA decay of IκBα, an inhibitor of proinflammatory nuclear factor-κB. These results reveal an atypical, mRNA metabolism-driven hypothalamic nuclear factor-κB activation, a mechanism that links obesity as well as aging to hypothalamic inflammation and ultimately to type 2 diabetes.

  9. The Effect of Age and NT-proBNP on the Association of Central Obesity with 6-Years Cardiovascular Mortality of Middle-Aged and Elderly Diabetic People: The Population-Based Casale Monferrato Study

    PubMed Central

    Bruno, Graziella; Barutta, Federica; Landi, Andrea; Cavallo Perin, Paolo; Gruden, Gabriella

    2014-01-01

    Background Among people with type 2 diabetes the relationship between central obesity and cardiovascular mortality has not been definitely assessed. Moreover, NT-proBNP is negatively associated with central obesity, but no study has examined their combined effect on survival. We have examined these issues in a well-characterized population-based cohort. Methods and Findings Survival data of 2272 diabetic people recruited in 2000 who had no other chronic disease have been updated to 31 December 2006. NT-proBNP was measured in a subgroup of 1690 patients. Cox proportional hazards modeling was employed to estimate the independent associations between cardiovascular and all-cause mortality and waist circumference. Mean age was 67.9 years, 49.3% were men. Both age and NT-proBNP were negatively correlated with waist circumference (r = −0.11, p<0.001 and r = −0.07, p = 0.002). Out of 2272 subjects, 520 deaths (221 for CV mortality) occurred during a median follow-up of 5.4 years. Central obesity was not associated with CV mortality (hazard ratio, HR, adjusted for age, sex, diabetes duration, 1.14, 95% CI 0.86–1.52). NTproBNP was a negative confounder and age a strong modifier of this relationship (p for interaction<0.001): age<70 years, fully adjusted model HR = 3.52 (1.17–10.57) and age ≥70 years, HR = 0.80 (0.46–1.40). Respective HRs for all-cause mortality were 1.86 (1.03–3.32) and 0.73 (0.51–1.04). Conclusions In diabetic people aged 70 years and lower, central obesity was independently associated with increased cardiovascular mortality, independently of the negative effect of NT-proBNP. In contrast, no effect on 6-years survival was evident in diabetic people who have yet survived up to 70 years. PMID:24788805

  10. Obesity in the ageing man.

    PubMed

    Michalakis, K; Goulis, D G; Vazaiou, A; Mintziori, G; Polymeris, A; Abrahamian-Michalakis, A

    2013-10-01

    As the population is ageing globally, both ageing and obesity are recognized as major public health challenges. The aim of this narrative review is to present and discuss the current evidence on the changes in body composition, energy balance and endocrine environment that occur in the ageing man. Obesity in the ageing man is related to changes in both body weight and composition due to alterations in energy intake and total energy expenditure. In addition, somatopenia (decreased GH secretion), late-onset hypogonadism (LOH), changes in thyroid and adrenal function, as well as changes in appetite-related peptides (leptin, ghrelin) and, most importantly, insulin action are related to obesity, abnormal energy balance, redistribution of the adipose tissue and sarcopenia (decreased muscle mass). A better understanding of the complex relationship of ageing-related endocrine changes and obesity could lead to more effective interventions for elderly men.

  11. Obesity and diabetes gene discovery approaches.

    PubMed

    Walder, K; Segal, D; Jowett, J; Blangero, J; Collier, G R

    2003-01-01

    New treatments are currently required for the common metabolic diseases obesity and type 2 diabetes. The identification of physiological and biochemical factors that underlie the metabolic disturbances observed in obesity and type 2 diabetes is a key step in developing better therapeutic outcomes. The discovery of new genes and pathways involved in the pathogenesis of these diseases is critical to this process, however identification of genes that contribute to the risk of developing these diseases represents a significant challenge as obesity and type 2 diabetes are complex diseases with many genetic and environmental causes. A number of diverse approaches have been used to discover and validate potential new targets for obesity and diabetes. To date, DNA-based approaches using candidate gene and genome-wide linkage analysis have had limited success in identifying genomic regions or genes involved in the development of these diseases. Recent advances in the ability to evaluate linkage analysis data from large family pedigrees using variance components based linkage analysis show great promise in robustly identifying genomic regions associated with the development of obesity and diabetes. RNA-based technologies such as cDNA microarrays have identified many genes differentially expressed in tissues of healthy and diseased subjects. Using a combined approach, we are endeavouring to focus attention on differentially expressed genes located in chromosomal regions previously linked with obesity and/or diabetes. Using this strategy, we have identified Beacon as a potential new target for obesity and diabetes.

  12. Neck Circumference as an Anthropometric Measure of Obesity in Diabetics

    PubMed Central

    Aswathappa, Jagadamba; Garg, Sumit; Kutty, Karthiyanee; Shankar, Vinutha

    2013-01-01

    Background: Obesity is a risk factor for type 2 diabetes mellitus. Insulin resistance is associated with visceral subcutaneous fat content. Neck circumference (NC) is a marker of upper body subcutaneous adipose tissue distribution. Aim: The aim of this study is to compare NC in diabetics and non-diabetics and to correlate NC with other anthropometric measures. Materials and Methods: A cross-sectional study was conducted in 350 type 2 diabetics and 350 non-diabetics of >30 years of age. Anthropometric parameters like body mass index (BMI), waist circumference (WC), hip circumference, and NC were measured. Independent t-test and Pearson's correlation were the tests of significance done to analyze quantitative data. Results: There was positive correlation of NC, BMI, and index of central obesity. The NC in diabetics was significantly higher than in non-diabetics (P < 0.001). NC >36 cm in diabetics and >37 cm in non-diabetics was the best cutoff value to determine subjects with central obesity. Conclusion: The findings indicated that NC may be used both in clinical practice and in epidemiologic studies as a straightforward and reliable index. It is an economical easy to use test with less consumption of time and correlates well with other standard anthropometric parameters. PMID:23378952

  13. Mitochondrial Plasticity in Obesity and Diabetes Mellitus

    PubMed Central

    Jelenik, Tomas

    2013-01-01

    Abstract Significance: Insulin resistance and its related diseases, obesity and type 2 diabetes mellitus (T2DM), have been linked to changes in aerobic metabolism, pointing to a possible role of mitochondria in the development of insulin resistance. Recent Advances: Refined methodology of ex vivo high-resolution respirometry and in vivo magnetic resonance spectroscopy now allows describing several features of mitochondria in humans. In addition to measuring mitochondrial function at baseline and after exercise-induced submaximal energy depletion, the response of mitochondria to endocrine and metabolic challenges, termed mitochondrial plasticity, can be assessed using hyperinsulinemic clamp tests. While insulin resistant states do not uniformly relate to baseline and post-exercise mitochondrial function, mitochondrial plasticity is typically impaired in insulin resistant relatives of T2DM, in overt T2DM and even in type 1 diabetes mellitus (T1DM). Critical Issues: The variability of baseline mitochondrial function in the main target tissue of insulin action, skeletal muscle and liver, may be attributed to inherited and acquired changes in either mitochondrial quantity or quality. In addition to certain gene polymorphisms and aging, circulating glucose and lipid concentrations correlate with both mitochondrial function and plasticity. Future Directions: Despite the associations between features of mitochondrial function and insulin sensitivity, the question of a causal relationship between compromised mitochondrial plasticity and insulin resistance in the development of obesity and T2DM remains to be resolved. Antioxid. Redox Signal. 19, 258–268. PMID:22938510

  14. Obesity-linked diabetes in the Arab world: a review.

    PubMed

    Abuyassin, B; Laher, I

    2015-09-08

    The Arab world is experiencing an epidemic of obesity and type 2 diabetes mellitus. This review summarizes the major pathological factors linking obesity to diabetes, focussing on current epidemiological data related to obese diabetic patients in the Arab world, the etiology of the disease and the genetic determinants of diabetes and obesity. There are alarming data related to the rising prevalence of obesity and type 2 diabetes mellitus in children of Arab ethnicity. Replication studies identify several genetic variants in Arabs with obesitylinked diabetes. For example, variants of the ADIPOQ gene (the rs266729 single-nucleotide polymorphism) are associated with obesity and diabetes in various Arab countries. Gaps exist in our information about diabetes and obesity in Arab populations in relation to ethnic-specific cut-off points for diagnosis and treatment of diabetes. Further genome-wide association studies in obese and diabetic Arab populations could add to our understanding of the pathophysiology, prevention and reversal of this disease.

  15. Oxidative Damage and Inflammation in Obese Diabetic Emirati Subjects

    PubMed Central

    Gariballa, Salah; Kosanovic, Melita; Yasin, Javed; El Essa, Awad

    2014-01-01

    Visceral obesity is more common in the Arab population and more closely related to morbidity, including diabetes and related cardiovascular diseases (CVD). Possible mechanisms that link visceral fat/obesity to diabetes and CVD complications include inflammation and increased oxidative stress; however, few data are available from the Arab population. Our aim was to determine whether increased adiposity in obese diabetic United Arab Emirates citizens is associated with sub-clinical inflammation and/or increased oxidative stress. A hundred diabetic patients who were part of a randomized controlled trial of nutritional supplements had their baseline characteristics assessed from anthropometric and clinical data following informed written consent. We used WHO figures to classify general and central obesity. Fasting blood samples were collected for the measurement of antioxidants and markers of oxidative damage and inflammation. We found that increased adiposity measured by both body mass index and waist circumference was associated with increased C-reactive protein (CRP) and decreased vitamin C after adjusting for age, duration and treatment of diabetes (p < 0.05). Although there is a clear trend of increased inflammatory markers, notably CRP, and decreased antioxidants with increased BMI and waist circumference in both men and women, the results are statistically significant for women only. CRP were also inversely associated with HDL. Overall, we found that BMI underestimates the rates of obesity compared to waist circumference and that increased adiposity is associated with increased inflammation and decreased HDL and antioxidant status. PMID:25375631

  16. The evil axis of obesity, inflammation and type-2 diabetes.

    PubMed

    Das, Arghya; Mukhopadhyay, Sangita

    2011-03-01

    Obesity and type 2 diabetes (T2D) are global problems affecting all age groups and have been characterized as lifestyle disorders. Though no study has clearly proved a direct correlation between obesity and T2D, a number of factors are associated with obesity causing insulin resistance and T2D. The factors such as adipokines and various transcription factors help to maintain a proper metabolic state in the body. Deregulation in any of these signalling balances due to obesity may trigger an inflammatory cascade which could lead to the aforesaid problems of insulin resistance and T2D. In this review, we have discussed the factors that probably link inflammation to obesity-induced insulin resistance and subsequently T2D and the possible therapeutic opportunities to decrease health risk of T2D in future. PMID:21348821

  17. Diabetes screening: a pending issue in hypertense/obese patients

    PubMed Central

    Sepehri, Armina; Gil-Guillén, Vicente Francisco; Ramírez-Prado, Dolores; Navarro-Cremades, Felipe; Cortés, Ernesto; Rizo-Baeza, María Mercedes

    2015-01-01

    The literature about possible cardiovascular consequences of diagnostic inertia in diabetes is scarce. We examined the influence of undetected high fasting blood glucose (FBG) levels on the cardiovascular risk and poor control of cardiovascular risk factors in hypertensive or obese patients, with no previous diagnosis of diabetes mellitus (i.e., diagnostic inertia). A cross-sectional study during a preventive program in a Spanish region was performed in 2003–2004. The participants were aged ≥40 years and did not have diabetes but were hypertensive (n = 5, 347) or obese (n = 7, 833). The outcomes were high cardiovascular risk (SCORE ≥5%), poor control of the blood pressure (≥140/90 mmHg) and class II obesity. The relationship was examined between FBG and the main parameters, calculating the adjusted odd ratios with multivariate models. Higher values of FBG were associated with all the outcomes. A more proactive attitude towards the diagnosis of diabetes mellitus in the hypertensive and obese population should be adopted. PMID:25922799

  18. Risk Factors for Subclinical Atherosclerosis in Diabetic and Obese Children

    PubMed Central

    Faienza, Maria Felicia; Acquafredda, Angelo; Tesse, Riccardina; Luce, Vincenza; Ventura, Annamaria; Maggialetti, Nicola; Monteduro, Mariantonietta; Giordano, Paola; Cavallo, Luciano

    2013-01-01

    Background. Increased carotid intima-media thickness (cIMT) is considered a marker of early-onset atherosclerosis and it seems to predict cardiovascular events both in obese and diabetic subjects. We aimed to evaluate early signs of atherosclerosis and investigate for predisposing factors in children and adolescents affected by type 1 diabetes (T1DM) or obesity, comparing them with healthy controls. Methods. Out of 71 enrolled subjects (mean age 12.8 ± 2.3 years), 26 had T1DM and 24 were obese, while 21 age- and sex-matched subjects acted as controls. cIMT was measured using standardized methods. Serum glucose, insulin, cholesterol, triglycerides and C-reactive protein levels were evaluated. An oral glucose tolerance test (OGTT) was performed in obese subjects. Results. Diabetic and obese individuals showed higher cIMT mean values than healthy controls (p<0.005). cIMT of the three examined segments correlated positively with fasting glucose levels and negatively with units of insulin/kg/day administered in T1DM individuals. A positive correlation between insulin levels (basal and after oral glucose load) and cIMT of common, internal and external carotid artery was found in obese subjects (p<0.03). High density cholesterol levels represented a protective factor for cIMT in this latter group of the study population. Conclusions. Our findings show that cIMT correlates with high insulin levels (a sign of insulin resistance) in obese patients and with high fasting glucose levels (a sign of relative insulin deficiency) in T1DM subjects, confirming the need of reducing hyperinsulinism and monitoring blood glucose levels in these subjects to prevent atherosclerosis. PMID:23423872

  19. Obesity and diabetes: A recipe for obstetric complications.

    PubMed

    Rosenn, Barak

    2008-03-01

    The prevalence of obesity has been increasing worldwide and has reached epidemic proportions in the United States, where well over 20% of the population have a body mass index (BMI) within the obese range. Obesity is associated with a wide spectrum of obstetric and perinatal complications, including increased risks of fetal mortality and morbidity, congenital malformations, maternal hypertensive disorders, gestational diabetes, excessive fetal growth and cesarean delivery. The odds ratios for these risks increase in direct correlation with the severity of obesity, and are significant even among women who are overweight without meeting criteria for obesity. Although obesity is closely associated with diabetes which, in itself, is associated with similar perinatal complications, diabetes and obesity are independent risk factors for adverse pregnancy outcome. Moreover, improving glycemic control in the pregnant woman with diabetes may mitigate the additive adverse effects of diabetes and obesity on pregnancy outcome.

  20. The Malnutrition of Obesity: Micronutrient Deficiencies That Promote Diabetes

    PubMed Central

    Via, Michael

    2012-01-01

    Obesity and diabetes are increasing in prevalence worldwide. Despite excessive dietary consumption, obese individuals have high rates of micronutrient deficiencies. Deficiencies of specific vitamins and minerals that play important roles in glucose metabolism and insulin signaling pathways may contribute to the development of diabetes in the obese population. This paper reviews the current evidence supporting this hypothesis. PMID:22462011

  1. Obesity and diabetes: from genetics to epigenetics.

    PubMed

    Burgio, Ernesto; Lopomo, Angela; Migliore, Lucia

    2015-04-01

    Obesity is becoming an epidemic health problem. During the last years not only genetic but also, and primarily, environmental factors have been supposed to contribute to the susceptibility to weight gain or to develop complications such as type 2 diabetes. In spite of the intense efforts to identify genetic predisposing variants, progress has been slow and success limited, and the common obesity susceptibility variants identified only explains a small part of the individual variation in risk. Moreover, there is evidence that the current epidemic of obesity and diabetes is environment-driven. Recent studies indicate that normal metabolic regulation during adulthood besides requiring a good balance between energy intake and energy expenditure, can be also affected by pre- and post-natal environments. In fact, maternal nutritional constraint during pregnancy can alter the metabolic phenotype of the offspring by means of epigenetic regulation of specific genes, and this can be passed to the next generations. Studies focused on epigenetic marks in obesity found altered methylation and/or histone acetylation levels in genes involved in specific but also in more general metabolic processes. Recent researches point out the continuous increase of "obesogens", in the environment and food chains, above all endocrine disruptors, chemicals that interfere with many homeostatic mechanisms. Taken into account the already existing data on the effects of obesogens, and the multiple potential targets with which they might interfere daily, it seems likely that the exposure to obesogens can have an important role in the obesity and diabesity pandemic.

  2. Non-Obese Diabetes and Its Associated Factors in an Underdeveloped Area of South China, Guangxi

    PubMed Central

    Tang, Zhenzhu; Fang, Zhifeng; Huang, Wei; Liu, Zhanhua; Chen, Yuzhu; Li, Zhongyou; Zhu, Ting; Wang, Qichun; Simpson, Steve; Taylor, Bruce V.; Lin, Rui

    2016-01-01

    Background: Little research has been conducted on the prevalence of diabetes mellitus in underdeveloped areas in China, especially stratified into obesity and non-obese diabetes. The aim of the present study was to investigate the prevalence and associated factors of non-obese diabetes in an underdeveloped area in South China, Guangxi. Methods: Data derived from the Chinese Health and Nutrition Survey 2010–2012 involved a sample of 3874 adults from Guangxi. Questionnaires and oral glucose-tolerance tests were conducted, and fasting and 2-h glucose levels and serum lipids were measured. Logistic regression analysis was performed to assess associated factors for non-obese diabetes. Results: 68.2% and 62.2% of instances of newly detected diabetes were those of non-obese diabetes based on BMI (NODB) and based on WC (NODW), respectively. The male sex, an age older than 50 years, lower education, hypertension, and hypertriglyceridemia were significantly associated with a higher risk of both NODB and NODW, while some associated factors for NODB were found different from those associated with NODW, and an interaction effect was found to increase the risk of NODW. Conclusions: Our study indicated that non-obese diabetes was highly prevalent in an underdeveloped area of South China. Non-obese diabetes should be considered for increased public attention in these areas. PMID:27706056

  3. [Epigenetics of childhood obesity and diabetes].

    PubMed

    Valladares-Salgado, Adán; Suárez-Sánchez, Fernando; Burguete-García, Ana I; Cruz, Miguel

    2014-01-01

    Obesity and type 2 diabetes mellitus (T2DM) result from sedentary lifestyle, high-carbohydrate diets and genetic predisposition. Epigenetics is a form of genetic regulation in specialized cells that does not involve changes in the deoxyribonucleic acid (DNA) sequence, but it can be inherited to one or more generations through mitosis or meiosis. Children whose mothers develop gestational diabetes are more likely to become obese and diabetic in adult life. DNA methylation is a major mechanism in the regulation of transcription and gene expression of several genes. High levels of glucose and insulin during pregnancy modify the risk of developing T2DM, suggesting that the expression pattern is modified due to cell memory in a specific tissue. If T2DM is linked to adaptation in utero, the obvious primary prevention is to protect the fetal development. Future epidemiological studies need to employ more accurate indicators or markers of development to show the relationship between a specific disease and the exposure to environmental factors. The mechanisms by which malnutrition, and intrauterine growth retardation produce changes in the metabolism of glucose and insuline are worth to explore in order to control obesity and T2DM. PMID:24866314

  4. [Epigenetics of childhood obesity and diabetes].

    PubMed

    Valladares-Salgado, Adán; Suárez-Sánchez, Fernando; Burguete-García, Ana I; Cruz, Miguel

    2014-01-01

    Obesity and type 2 diabetes mellitus (T2DM) result from sedentary lifestyle, high-carbohydrate diets and genetic predisposition. Epigenetics is a form of genetic regulation in specialized cells that does not involve changes in the deoxyribonucleic acid (DNA) sequence, but it can be inherited to one or more generations through mitosis or meiosis. Children whose mothers develop gestational diabetes are more likely to become obese and diabetic in adult life. DNA methylation is a major mechanism in the regulation of transcription and gene expression of several genes. High levels of glucose and insulin during pregnancy modify the risk of developing T2DM, suggesting that the expression pattern is modified due to cell memory in a specific tissue. If T2DM is linked to adaptation in utero, the obvious primary prevention is to protect the fetal development. Future epidemiological studies need to employ more accurate indicators or markers of development to show the relationship between a specific disease and the exposure to environmental factors. The mechanisms by which malnutrition, and intrauterine growth retardation produce changes in the metabolism of glucose and insuline are worth to explore in order to control obesity and T2DM.

  5. [Intestinal microflora, obesity and type 2 diabetes].

    PubMed

    Bondarenko, V M; Maleev, V V; Likhoded, V G

    2014-01-01

    The review of data of the literature on a role of intestinal microflora, genetic features of a macroorganism, exogenic factors and character of a food is presented at obesity and a type 2 diabetes. Researches establish, that development in experimental animals of the induced obesity and the type 2 diabetes, depends on a diet and presence of intestinal microflora. The factors increasing permeability mucous intestines, promote a translocation of intestinal automicroflora and its toxins into macroorganism and a system blood-circulation. Long introduction LPS (endotoxin) of gram-negative bacteria to the special laboratory animals led to development of inflammatory reaction, adiposity and resistance to insulin. The specified phenomena did not develop at LPS introduction to the animals, who have lost receptor CD14 which is necessary for linkage and endotoxin action. Data about change of intestinal microflora and a role of immune infringements are discussed at obesity and the type 2 diabetes occurring into background of low-grade chronic inflammation and metabolic disorders.

  6. Depression Amplifies the Influence of Central Obesity on 10-Year Incidence of Diabetes: Findings from MIDUS

    PubMed Central

    Karlamangla, Arun

    2016-01-01

    Background Central obesity is a major risk factor for diabetes but many obese individuals never develop diabetes, suggesting the presence of important effect modifiers. Depression has emerged as a key risk factor for poor glycemic control, but to our knowledge, no previous work has investigated whether depression amplifies the effect of central obesity on glucoregulation. Methods and Findings We used a national sample of adults without prevalent diabetes (MIDUS; N = 919) to test for synergy between central obesity and depression in the development of diabetes 10 years later. We found that depression amplified the association of waist-to-hip ratio (WHR) with incident diabetes adjusted for age, race, gender, education, physical activity, and sleep problems (p = 0.01 for test of interaction). The relative risk for incident diabetes per every 0.1 increment in WHR was 1.75 (95% CI: 1.31; 2.33) in those without depression and 3.78 in those with depression (95% CI: 2.14; 6.66). Conclusions These results confirm the role of depression as a robust risk factor for the development of diabetes and for the first time, demonstrate a synergy between depression and central obesity. Identifying and addressing depression could prove to be an effective approach to preventing diabetes in at risk individuals. Ultimately, elucidating the interplay among risk factors from different domains will be key to understanding multifactorial diseases such as diabetes and informing theory-based, patient-centered interventions aimed at reducing diabetes risk. PMID:27755576

  7. AGE restriction in diabetes mellitus: a paradigm shift.

    PubMed

    Vlassara, Helen; Striker, Gary E

    2011-05-24

    Persistently elevated oxidative stress and inflammation precede or occur during the development of type 1 or type 2 diabetes mellitus and precipitate devastating complications. Given the rapidly increasing incidence of diabetes mellitus and obesity in the space of a few decades, new genetic mutations are unlikely to be the cause, instead pointing to environmental initiators. A hallmark of contemporary culture is a preference for thermally processed foods, replete with pro-oxidant advanced glycation endproducts (AGEs). These molecules are appetite-increasing and, thus, efficient enhancers of overnutrition (which promotes obesity) and oxidant overload (which promotes inflammation). Studies of genetic and nongenetic animal models of diabetes mellitus suggest that suppression of host defenses, under sustained pressure from food-derived AGEs, may potentially shift homeostasis towards a higher basal level of oxidative stress, inflammation and injury of both insulin-producing and insulin-responsive cells. This sequence promotes both types of diabetes mellitus. Reducing basal oxidative stress by AGE restriction in mice, without energy or nutrient change, reinstates host defenses, alleviates inflammation, prevents diabetes mellitus, vascular and renal complications and extends normal lifespan. Studies in healthy humans and in those with diabetes mellitus show that consumption of high amounts of food-related AGEs is a determinant of insulin resistance and inflammation and that AGE restriction improves both. This Review focuses on AGEs as novel initiators of oxidative stress that precedes, rather than results from, diabetes mellitus. Therapeutic gains from AGE restriction constitute a paradigm shift.

  8. Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring

    PubMed Central

    Glastras, Sarah J.; Tsang, Michael; Teh, Rachel; Chen, Hui; McGrath, Rachel T.; Zaky, Amgad A.; Pollock, Carol A.; Saad, Sonia

    2016-01-01

    Maternal obesity is known to increase the risk of obesity and diabetes in offspring. Though diabetes is a key risk factor for the development of chronic kidney disease (CKD), the relationship between maternal obesity and CKD has not been clearly defined. In this study, a mouse model of maternal obesity was employed to determine the impact of maternal obesity on development of diabetic nephropathy in offspring. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow diet. At postnatal Week 8, offspring were randomly administered low dose streptozotocin (STZ, 55 mg/kg/day for five days) to induce diabetes. Assessment of renal damage took place at postnatal Week 32. We found that offspring of obese mothers had increased renal fibrosis, inflammation and oxidative stress. Importantly, offspring exposed to maternal obesity had increased susceptibility to renal damage when an additional insult, such as STZ-induced diabetes, was imposed. Specifically, renal inflammation and oxidative stress induced by diabetes was augmented by maternal obesity. Our findings suggest that developmental programming induced by maternal obesity has implications for renal health in offspring. Maternal obesity should be considered a risk factor for CKD. PMID:27277011

  9. Childhood obesity affects adult metabolic syndrome and diabetes.

    PubMed

    Liang, Yajun; Hou, Dongqing; Zhao, Xiaoyuan; Wang, Liang; Hu, Yuehua; Liu, Junting; Cheng, Hong; Yang, Ping; Shan, Xinying; Yan, Yinkun; Cruickshank, J Kennedy; Mi, Jie

    2015-09-01

    We seek to observe the association between childhood obesity by different measures and adult obesity, metabolic syndrome (MetS), and diabetes. Thousand two hundred and nine subjects from "Beijing Blood Pressure Cohort Study" were followed 22.9 ± 0.5 years in average from childhood to adulthood. We defined childhood obesity using body mass index (BMI) or left subscapular skinfold (LSSF), and adult obesity as BMI ≥ 28 kg/m(2). MetS was defined according to the joint statement of International Diabetes Federation and American Heart Association with modified waist circumference (≥ 90/85 cm for men/women). Diabetes was defined as fasting plasma glucose ≥ 7.0 mmol/L or blood glucose 2 h after oral glucose tolerance test ≥ 11.1 mmol/L or currently using blood glucose-lowering agents. Multiple linear and logistic regression models were used to assess the association. The incidence of adult obesity was 13.4, 60.0, 48.3, and 65.1 % for children without obesity, having obesity by BMI only, by LSSF only, and by both, respectively. Compared to children without obesity, children obese by LSSF only or by both had higher risk of diabetes. After controlling for adult obesity, childhood obesity predicted independently long-term risks of diabetes (odds ratio 2.8, 95 % confidence interval 1.2-6.3) or abdominal obesity (2.7, 1.6-4.7) other than MetS as a whole (1.2, 0.6-2.4). Childhood obesity predicts long-term risk of adult diabetes, and the effect is independent of adult obesity. LSSF is better than BMI in predicting adult diabetes.

  10. The origins and consequences of obesity. Diabetes.

    PubMed

    Björntorp, P

    1996-01-01

    A relationship exists between obesity and non-insulin-dependent diabetes mellitus. Central, abdominal obesity carries a particularly high risk that is most likely associated with enlargement of visceral fat deposits. A multiple endocrine perturbation is associated with visceral obesity. This consists of a hypersensitive hypothalamic-pituitary-adrenal (HPA) axis, with resulting excess of cortisol secretion upon stimulation. Growth hormone levels in both sexes are diminished and testosterone concentrations in men are lower than normal. In women a moderate hyperandrogenism is often present. The elevated sensitivity of the HPA axis may be a primary event, followed by adrenal androgen production in women and by interaction at several levels, with inhibition of both the growth hormone and pituitary-gonadal axes. Together, these endocrine perturbations seem to be able to centralize body fat to visceral depots because of a high density of steroid hormone receptors. The endocrine perturbations are most likely followed by insulin resistance. Elevated cortisol levels, deficiencies in sex-specific steroid hormones and excess androgens result in insulin resistance. The endocrine abnormalities in visceral obesity are followed by insulin resistance, both directly and indirectly via contribution of excess free fatty acids from centralized body fat depots. The hyperactivity of the HPA axis may be due to frequent challenges and it is amplified by a deficient feedback inhibition. A depressive, helplessness reaction to stress may be involved. Such stress factors may be found in socioeconomic and psychosocial handicaps, as suggested by results of population studies. This hypothesis is strongly supported by the reproduction of an identical condition in non-human primates that react with a depressive reaction upon psychosocial types of stressors. The perturbations of the HPA axis may thus be in the centre of the syndrome. Studies of this axis in established non-insulin-dependent diabetes

  11. TRP Channels as Therapeutic Targets in Diabetes and Obesity.

    PubMed

    Zsombok, Andrea; Derbenev, Andrei V

    2016-01-01

    During the last three to four decades the prevalence of obesity and diabetes mellitus has greatly increased worldwide, including in the United States. Both the short- and long-term forecasts predict serious consequences for the near future, and encourage the development of solutions for the prevention and management of obesity and diabetes mellitus. Transient receptor potential (TRP) channels were identified in tissues and organs important for the control of whole body metabolism. A variety of TRP channels has been shown to play a role in the regulation of hormone release, energy expenditure, pancreatic function, and neurotransmitter release in control, obese and/or diabetic conditions. Moreover, dietary supplementation of natural ligands of TRP channels has been shown to have potential beneficial effects in obese and diabetic conditions. These findings raised the interest and likelihood for potential drug development. In this mini-review, we discuss possibilities for better management of obesity and diabetes mellitus based on TRP-dependent mechanisms. PMID:27548188

  12. TRP Channels as Therapeutic Targets in Diabetes and Obesity

    PubMed Central

    Zsombok, Andrea; Derbenev, Andrei V.

    2016-01-01

    During the last three to four decades the prevalence of obesity and diabetes mellitus has greatly increased worldwide, including in the United States. Both the short- and long-term forecasts predict serious consequences for the near future, and encourage the development of solutions for the prevention and management of obesity and diabetes mellitus. Transient receptor potential (TRP) channels were identified in tissues and organs important for the control of whole body metabolism. A variety of TRP channels has been shown to play a role in the regulation of hormone release, energy expenditure, pancreatic function, and neurotransmitter release in control, obese and/or diabetic conditions. Moreover, dietary supplementation of natural ligands of TRP channels has been shown to have potential beneficial effects in obese and diabetic conditions. These findings raised the interest and likelihood for potential drug development. In this mini-review, we discuss possibilities for better management of obesity and diabetes mellitus based on TRP-dependent mechanisms. PMID:27548188

  13. The epidemiology and molecular mechanisms linking obesity, diabetes, and cancer.

    PubMed

    Ferguson, Rosalyn D; Gallagher, Emily J; Scheinman, Eyal J; Damouni, Rawan; LeRoith, Derek

    2013-01-01

    The worldwide epidemic of obesity is associated with increasing rates of the metabolic syndrome and type 2 diabetes. Epidemiological studies have reported that these conditions are linked to increased rates of cancer incidence and mortality. Obesity, particularly abdominal obesity, is associated with insulin resistance and the development of dyslipidemia, hyperglycemia, and ultimately type 2 diabetes. Although many metabolic abnormalities occur with obesity and type 2 diabetes, insulin resistance and hyperinsulinemia appear to be central to these conditions and may contribute to dyslipidemia and altered levels of circulating estrogens and androgens. In this review, we will discuss the epidemiological and molecular links between obesity, type 2 diabetes, and cancer, and how hyperinsulinemia and dyslipidemia may contribute to cancer development. We will discuss how these metabolic abnormalities may interact with estrogen signaling in breast cancer growth. Finally, we will discuss the effects of type 2 diabetes medications on cancer risk. PMID:23810003

  14. DIABETES, OBESITY AND DIAGNOSIS OF AMYOTROPHIC LATERAL SCLEROSIS: A POPULATION-BASED STUDY

    PubMed Central

    Kioumourtzoglou, Marianthi-Anna; Rotem, Ran S.; Seals, Ryan M.; Gredal, Ole; Hansen, Johnni; Weisskopf, Marc G.

    2016-01-01

    Importance Although prior studies have suggested a role of cardiometabolic health on pathogenesis of amyotrophic lateral sclerosis (ALS), the association with diabetes has not been widely examined. Objective Amyotrophic lateral sclerosis is the most common motor neuron disorder. Several vascular risk factors have been associated with decreased risk for ALS. Although diabetes is also a risk factor for vascular disease, the few studies of diabetes and ALS have been inconsistent. We examined the association between diabetes and obesity, each identified through ICD-8 or 10 codes in a hospital registry, and ALS using data from the Danish National Registers. Design and Setting Population-based nested case-control study. Participants 3,650 Danish residents diagnosed with ALS between 1982 and 2009, and 365,000 controls (100 for each ALS case), matched on age and sex. Main Outcome Measure Adjusted odds ratio (OR) for ALS associated with diabetes or obesity diagnoses at least three years prior to the ALS diagnosis date. Results When considering diabetes and our obesity indicator together, the estimated OR for ALS was 0.61 (95%CI: 0.46–0.80) for diabetes and 0.81 (95%CI: 0.57–1.16) for obesity. We observed no effect modification on the association with diabetes by gender, but a significant modification by age at first diabetes or age at ALS, with the protective association stronger with increasing age, consistent with different associations by diabetes type. Conclusions and Relevance We conducted a nationwide study to investigate the association between diabetes and ALS diagnosis. Our findings are in agreement with previous reports of a protective association between vascular risk factors and ALS, and suggest type 2 diabetes, but not type 1, is protective for ALS. PMID:26030836

  15. Oxytocin and cardioprotection in diabetes and obesity.

    PubMed

    Jankowski, Marek; Broderick, Tom L; Gutkowska, Jolanta

    2016-01-01

    Oxytocin (OT) emerges as a drug for the treatment of diabetes and obesity. The entire OT system is synthesized in the rat and human heart. The direct myocardial infusion with OT into an ischemic or failing heart has the potential to elicit a variety of cardioprotective effects. OT treatment attenuates cardiomyocyte (CMs) death induced by ischemia-reperfusion by activating pro-survival pathways within injured CMs in vivo and in isolated cells. OT treatment reduces cardiac apoptosis, fibrosis, and hypertrophy. The OT/OT receptor (OTR) system is downregulated in the db/db mouse model of type 2 diabetes which develops genetic diabetic cardiomyopathy (DC) similar to human disease. We have shown that chronic OT treatment prevents the development of DC in the db/db mouse. In addition, OT stimulates glucose uptake in both cardiac stem cells and CMs, and increases cell resistance to diabetic conditions. OT may help replace lost CMs by stimulating the in situ differentiation of cardiac stem cells into functional mature CMs. Lastly, adult stem cells amenable for transplantation such as MSCs could be preconditioned with OT ex vivo and implanted into the injured heart to aid in tissue regeneration through direct differentiation, secretion of protective and cardiomyogenic factors and/or their fusion with injured CMs. PMID:27268060

  16. Oxytocin and cardioprotection in diabetes and obesity.

    PubMed

    Jankowski, Marek; Broderick, Tom L; Gutkowska, Jolanta

    2016-06-07

    Oxytocin (OT) emerges as a drug for the treatment of diabetes and obesity. The entire OT system is synthesized in the rat and human heart. The direct myocardial infusion with OT into an ischemic or failing heart has the potential to elicit a variety of cardioprotective effects. OT treatment attenuates cardiomyocyte (CMs) death induced by ischemia-reperfusion by activating pro-survival pathways within injured CMs in vivo and in isolated cells. OT treatment reduces cardiac apoptosis, fibrosis, and hypertrophy. The OT/OT receptor (OTR) system is downregulated in the db/db mouse model of type 2 diabetes which develops genetic diabetic cardiomyopathy (DC) similar to human disease. We have shown that chronic OT treatment prevents the development of DC in the db/db mouse. In addition, OT stimulates glucose uptake in both cardiac stem cells and CMs, and increases cell resistance to diabetic conditions. OT may help replace lost CMs by stimulating the in situ differentiation of cardiac stem cells into functional mature CMs. Lastly, adult stem cells amenable for transplantation such as MSCs could be preconditioned with OT ex vivo and implanted into the injured heart to aid in tissue regeneration through direct differentiation, secretion of protective and cardiomyogenic factors and/or their fusion with injured CMs.

  17. Diabetes, Diet-Health Behavior, and Obesity

    PubMed Central

    Anders, Sven; Schroeter, Christiane

    2015-01-01

    High-quality diets play an important role in diabetes prevention. Appropriate dietary adherence can improve insulin sensitivity and glycemic control, and thus contribute to lifestyle improvement. However, previous research suggests that dietary adherence is arguably among the most difficult cornerstones of diabetes management. The objectives of this study are (1) to estimate whether and to what extent individuals diagnosed with diabetes show significant differences in diet quality [healthy eating index (HEI)] compared to healthy individuals, (2) to quantify whether and to what extent diabetics experience significantly higher outcomes of body mass index (BMI), and (3) to estimate whether and to what extent dietary supplementation impacts diabetes patient’s diet quality and/or BMI outcomes. We use data from the 2007–2008 U.S. National Health and Nutrition Examination Survey (NHANES). The NHANES is the primary, randomized, and nationally representative survey used to assess the health and nutritional status in the U.S. We apply propensity score matching (PSM) to account for selection bias and endogeneity between self-reported diet and health behavir (treatment) and BMI outcomes. We control for an individual’s BMI as to capture the impact of past dietary behavior in its impact on HEI. Matching results suggest that regular dietary supplement consumption is associated with significant lower BMI outcomes of almost 1 kg/m2. The close relationship between diabetes and obesity has been at the center of the diet-health policy debate across Canada and the U.S. Knowledge about this linkage may help to improve the understanding of the factors that impact dietary choices and their overall health outcomes, which may lead to a more efficient and effective promotion of dietary guidelines, healthy food choices, and targeted consumer health and lifestyle policies. PMID:25852643

  18. Diabetes, diet-health behavior, and obesity.

    PubMed

    Anders, Sven; Schroeter, Christiane

    2015-01-01

    High-quality diets play an important role in diabetes prevention. Appropriate dietary adherence can improve insulin sensitivity and glycemic control, and thus contribute to lifestyle improvement. However, previous research suggests that dietary adherence is arguably among the most difficult cornerstones of diabetes management. The objectives of this study are (1) to estimate whether and to what extent individuals diagnosed with diabetes show significant differences in diet quality [healthy eating index (HEI)] compared to healthy individuals, (2) to quantify whether and to what extent diabetics experience significantly higher outcomes of body mass index (BMI), and (3) to estimate whether and to what extent dietary supplementation impacts diabetes patient's diet quality and/or BMI outcomes. We use data from the 2007-2008 U.S. National Health and Nutrition Examination Survey (NHANES). The NHANES is the primary, randomized, and nationally representative survey used to assess the health and nutritional status in the U.S. We apply propensity score matching (PSM) to account for selection bias and endogeneity between self-reported diet and health behavir (treatment) and BMI outcomes. We control for an individual's BMI as to capture the impact of past dietary behavior in its impact on HEI. Matching results suggest that regular dietary supplement consumption is associated with significant lower BMI outcomes of almost 1 kg/m(2). The close relationship between diabetes and obesity has been at the center of the diet-health policy debate across Canada and the U.S. Knowledge about this linkage may help to improve the understanding of the factors that impact dietary choices and their overall health outcomes, which may lead to a more efficient and effective promotion of dietary guidelines, healthy food choices, and targeted consumer health and lifestyle policies.

  19. 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.

  20. Epigenetics in adipose tissue, obesity, weight loss, and diabetes.

    PubMed

    Martínez, J Alfredo; Milagro, Fermín I; Claycombe, Kate J; Schalinske, Kevin L

    2014-01-01

    Given the role that diet and other environmental factors play in the development of obesity and type 2 diabetes, the implication of different epigenetic processes is being investigated. Although it is well known that external factors can cause cell type-dependent epigenetic changes, including DNA methylation, histone tail modifications, and chromatin remodeling, the regulation of these processes, the magnitude of the changes and the cell types in which they occur, the individuals more predisposed, and the more crucial stages of life remain to be elucidated. There is evidence that obese and diabetic people have a pattern of epigenetic marks different from nonobese and nondiabetic individuals. The main long-term goals in this field are the identification and understanding of the role of epigenetic marks that could be used as early predictors of metabolic risk and the development of drugs or diet-related treatments able to delay these epigenetic changes and even reverse them. But weight gain and insulin resistance/diabetes are influenced not only by epigenetic factors; different epigenetic biomarkers have also been identified as early predictors of weight loss and the maintenance of body weight after weight loss. The characterization of all the factors that are able to modify the epigenetic signatures and the determination of their real importance are hindered by the following factors: the magnitude of change produced by dietary and environmental factors is small and cumulative; there are great differences among cell types; and there are many factors involved, including age, with multiple interactions between them. PMID:24425725

  1. Type 2 Diabetes Treatment in the Patient with Obesity.

    PubMed

    Malin, Steven K; Kashyap, Sangeeta R

    2016-09-01

    Lifestyle modification is the cornerstone treatment of type 2 diabetes in the obese patient, and is highly effective at promoting glucose regulation. However, many individuals struggle over time to maintain optimal glycemic control and/or body weight with lifestyle modification. Therefore, additional therapeutic approaches are needed. Pharmacologic interventions have shown promising results for obesity-related diabetes complications. Not surprisingly though lifestyle modification and pharmacology may become ineffective for treating diabetes over time. Bariatric surgery is considered by some, but not all, to be the most effective and durable treatment for combating obesity. In fact many patients with type 2 diabetes have normalized glucose concentrations within days postoperation. Taken together, treatment of obesity in the patient with type 2 diabetes requires a multi-faceted approach. PMID:27519130

  2. Obesity and diabetes in TNF-alpha receptor- deficient mice.

    PubMed Central

    Schreyer, S A; Chua, S C; LeBoeuf, R C

    1998-01-01

    TNF-alpha may play a role in mediating insulin resistance associated with obesity. This concept is based on studies of obese rodents and humans, and cell culture models. TNF elicits cellular responses via two receptors called p55 and p75. Our purpose was to test the involvement of TNF in glucose homeostasis using mice lacking one or both TNF receptors. C57BL/6 mice lacking p55 (p55(-)/-), p75, (p75(-)/-), or both receptors (p55(-)/-p75(-)/-) were fed a high-fat diet to induce obesity. Marked fasting hyperinsulinemia was seen for p55(-)/-p75(-)/- males between 12 and 16 wk of feeding the high-fat diet. Insulin levels were four times greater than wild-type mice. In contrast, p55(-)/- and p75(-)/- mice exhibited insulin levels that were similar or reduced, respectively, as compared with wild-type mice. In addition, high-fat diet-fed p75(-)/- mice had the lowest body weights and leptin levels, and improved insulin sensitivity. Obese (db/db) mice, which are not responsive to leptin, were used to study the role of p55 in severe obesity. Male p55(-)/-db/db mice exhibited threefold higher insulin levels and twofold lower glucose levels at 20 wk of age than control db/db expressing p55. All db/db mice remained severely insulin resistant based on fasting plasma glucose and insulin levels, and glucose and insulin tolerance tests. Our data do not support the concept that TNF, acting via its receptors, is a major contributor to obesity-associated insulin resistance. In fact, data suggest that the two TNF receptors work in concert to protect against diabetes. PMID:9664082

  3. The investigation of the some body parameters of obese and (obese+diabetes) patients with using bioelectrical impedance analysis techniques

    NASA Astrophysics Data System (ADS)

    Yerlikaya, Emrah; Karageçili, Hasan; Aydin, Ruken Zeynep

    2016-04-01

    Obesity is a key risk for the development of hyperglycemia, hypertension, hyperlipidemia, insulin resistance and is totally referred to as the metabolic disorders. Diabetes mellitus, a metabolic disorder, is related with hyperglycemia, altered metabolism of lipids, carbohydrates and proteins. The minimum defining characteristic feature to identify diabetes mellitus is chronic and substantiated elevation of circulating glucose concentration. In this study, it is aimed to determine the body composition analyze of obese and (obese+diabetes) patients.We studied the datas taken from three independent groups with the body composition analyzer instrument. The body composition analyzer calculates body parameters, such as body fat ratio, body fat mass, fat free mass, estimated muscle mass, and base metabolic rate on the basis of data obtained by Dual Energy X-ray Absorptiometry using Bioelectrical Impedance Analysis. All patients and healthy subjects applied to Siirt University Medico and their datas were taken. The Statistical Package for Social Sciences version 21 was used for descriptive data analysis. When we compared and analyzed three groups datas, we found statistically significant difference between obese, (obese+diabetes) and control groups values. Anova test and tukey test are used to analyze the difference between groups and to do multiple comparisons. T test is also used to analyze the difference between genders. We observed the statistically significant difference in age and mineral amount p<0.00 between (diabetes+obese) and obese groups. Besides, when these patient groups and control group were analyzed, there were significant difference between most parameters. In terms of education level among the illiterate and university graduates; fat mass kg, fat percentage, internal lubrication, body mass index, water percentage, protein mass percentage, mineral percentage p<0.05, significant statistically difference were observed. This difference especially may result

  4. Effect of obesity and type 2 diabetes on protein anabolic response to insulin in elderly women.

    PubMed

    Murphy, Jessica; Chevalier, Stéphanie; Gougeon, Réjeanne; Goulet, Éric D B; Morais, José A

    2015-09-01

    Obesity and type 2 diabetes have been shown to alter the insulin sensitivity of glucose and protein metabolism in middle-aged women. We aimed to determine whether these findings translate to the elderly who are at increased risk of muscle loss. We assessed whole-body protein (1-(13)C-leucine) and glucose (3-(3)H-glucose) kinetics in 10 healthy (age: 71.6±1.8years; BMI: 23.2±0.8kg/m(2)), 8 obese (age: 72.9±1.3; BMI: 33.1±1.0) and 8 obese well-controlled type 2 diabetic (age: 69.8±1.6; BMI: 34.4±1.5) elderly women in the postabsorptive state and during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp. All subjects followed an isoenergetic, protein-controlled diet for 6days preceding the clamp. The net protein anabolic response to hyperinsulinemia was similarly blunted in obese (0.08±0.06) and obese type 2 diabetic women (0.06±0.04) compared to healthy women (0.24±0.05μmol·kg fat free mass(-1)·min(-1); ANOVA p=0.018). In contrast, the insulin-mediated glucose disposal (healthy: 9.72±0.67) was decreased with obesity (6.96±0.86) and further with diabetes (5.23±0.27mg·kg fat free mass(-1)·min(-1); ANOVA p<0.001). Endogenous glucose production was not completely suppressed during the clamp only in diabetic women. Thus, the glucose infusion rate was the lowest in this group. Obese elderly women with and without type 2 diabetes have a similar degree of insulin resistance of protein anabolism, despite worse glucose metabolism in type 2 diabetes. Similar to previous findings in middle-aged women, obesity exerted a blunting effect on protein anabolism, which may contribute to the development of sarcopenic obesity. Our results suggest that the presence of type 2 diabetes at an advancing age does not further aggravate this effect. PMID:26068615

  5. Dietary proteins in obesity and in diabetes.

    PubMed

    Keller, Ulrich

    2011-03-01

    Dietary proteins influence body weight by affecting four targets for body weight regulation: satiety, thermogenesis, energy efficiency, and body composition. Protein ingestion results in higher ratings of satiety than equicaloric amounts of carbohydrates or fat. Their effect on satiety is mainly due to oxidation of amino acids fed in excess; this effect is higher with ingestion of specific "incomplete" proteins (vegetal) than with animal proteins. Diet-induced thermogenesis is higher for proteins than for other macronutrients. The increase in energy expenditure is caused by protein and urea synthesis and by gluconeogenesis. This effect is higher with animal proteins containing larger amounts of essential amino acids than with vegetable proteins. Specifically, diet-induced thermogenesis increases after protein ingestion by 20 - 30 %, but by only 5 - 10 % after carbohydrates and 0 - 5 % after ingestion of fat. Consumption of higher amounts of protein during dietary treatment of obesity resulted in greater weight loss than with lower amounts of protein in dietary studies lasting up to one year. During weight loss and decreased caloric intake, a relatively increased protein content of the diet maintained fat-free mass (i. e. muscle mass) and increased calcium balance, resulting in preservation of bone mineral content. This is of particular importance during weight loss after bariatric surgery because these patients are at risk for protein malnutrition. Adequate dietary protein intake in diabetes type 2 is of specific importance since proteins are relatively neutral with regard to glucose and lipid metabolism, and they preserve muscle and bone mass, which may be decreased in subjects with poorly controlled diabetes. Ingestion of dietary proteins in diabetes type 1 exerts a delayed postprandial increase in blood glucose levels due to protein-induced stimulation of pancreatic glucagon secretion. Higher than minimal amounts of protein in the diet needed for nitrogen

  6. Therapeutic Phytogenic Compounds for Obesity and Diabetes

    PubMed Central

    Jung, Hee Soong; Lim, Yun; Kim, Eun-Kyoung

    2014-01-01

    Natural compounds have been used to develop drugs for many decades. Vast diversities and minimum side effects make natural compounds a good source for drug development. However, the composition and concentrations of natural compounds can vary. Despite this inconsistency, half of the Food and Drug Administration (FDA)-approved pharmaceuticals are natural compounds or their derivatives. Therefore, it is essential to continuously investigate natural compounds as sources of new pharmaceuticals. This review provides comprehensive information and analysis on natural compounds from plants (phytogenic compounds) that may serve as anti-obesity and/or anti-diabetes therapeutics. Our growing understanding and further exploration of the mechanisms of action of the phytogenic compounds may afford opportunities for development of therapeutic interventions in metabolic diseases. PMID:25421245

  7. [Estrogen receptor alpha in obesity and diabetes].

    PubMed

    Cahua-Pablo, José Ángel; Flores-Alfaro, Eugenia; Cruz, Miguel

    2016-01-01

    Estradiol (E2) is an important hormone in reproductive physiology, cardiovascular, skeletal and in the central nervous system (CNS). In human and rodents, E2 and its receptors are involved in the control of energy and glucose metabolism in health and metabolic diseases. The estrogen receptor (ER) belongs to the superfamily of nuclear receptors (NR), which are transcription factors that regulate gene expression. Three ER, ER-alpha, ER-beta and the G protein-coupled ER (GPER; also called GPR30) in tissues are involved in glucose and lipid homeostasis. Also, it may have important implications for risk factors associated with metabolic syndrome (MS), insulin resistance (IR), obesity and type 2 diabetes (T2D).

  8. Obesity upregulates genes involved in oxidative phosphorylation in livers of diabetic patients.

    PubMed

    Takamura, Toshinari; Misu, Hirofumi; Matsuzawa-Nagata, Naoto; Sakurai, Masaru; Ota, Tsuguhito; Shimizu, Akiko; Kurita, Seiichiro; Takeshita, Yumie; Ando, Hitoshi; Honda, Masao; Kaneko, Shuichi

    2008-12-01

    Obesity is a major cause of insulin resistance and contributes to the development of type 2 diabetes. The altered expression of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) has been regarded as a key change in insulin-sensitive organs of patients with type 2 diabetes. This study explores possible molecular signatures of obesity and examines the clinical significance of OXPHOS gene expression in the livers of patients with type 2 diabetes. We analyzed gene expression in the livers of 21 patients with type 2 diabetes (10 obese and 11 nonobese patients; age, 53.0 +/- 2.1 years; BMI, 24.4 +/- 0.9 kg/m(2); fasting plasma glucose, 143.0 +/- 10.6 mg/dl) using a DNA chip. We screened 535 human pathways and extracted those metabolic pathways significantly altered by obesity. Genes involved in the OXPHOS pathway, together with glucose and lipid metabolism pathways, were coordinately upregulated in the liver in association with obesity. The mean centroid of OXPHOS gene expression was significantly correlated with insulin resistance indices and the hepatic expression of genes involved in gluconeogenesis, reactive oxygen species (ROS) generation, and transcriptional factors and nuclear co-activators associated with energy homeostasis. In conclusion, obesity may affect the pathophysiology of type 2 diabetes by upregulating genes involved in OXPHOS in association with insulin resistance markers and the expression of genes involved in hepatic gluconeogenesis and ROS generation.

  9. Monocyte Chemoattractant Protein 1 (MCP-1) in Obesity and Diabetes

    PubMed Central

    Panee, Jun

    2012-01-01

    Monocyte chemoattractant protein-1 (MCP-1) is the first discovered and most extensively studied CC chemokine, and the amount of studies on its role in the etiologies of obesity- and diabetes-related diseases have increased exponentially during the past 2 decades. This review attempted to provide a panoramic perspective of the history, regulatory mechanisms, functions, and therapeutic strategies of this chemokine. The highlights of this review include the roles of MCP-1 in the development of obesity, diabetes, cardiovascular diseases, insulitis, diabetic nephropathy, and diabetic retinopathy. Therapies that specifically or non-specifically inhibit MCP-1 overproduction have been summarized. PMID:22766373

  10. [Type 2 diabetes, obesity and nutrition, a paradigm shift].

    PubMed

    Bourcelot, Emilie; Combes, Jérôme

    2016-05-01

    Obesity and type 2 diabetes are two complex and multifactorial chronic diseases. Nutritional management is based on an educational and bio-psycho-sensory approach centred on the patient using cognitive-behavioural and emotionally-focused therapy tools.

  11. Family history: an opportunity for early interventions and improved control of hypertension, obesity and diabetes.

    PubMed Central

    van der Sande, M. A.; Walraven, G. E.; Milligan, P. J.; Banya, W. A.; Ceesay, S. M.; Nyan, O. A.; McAdam, K. P.

    2001-01-01

    OBJECTIVE: To examine whether a family history of high-risk groups for major noncommunicable diseases (NCDs) was a significant risk factor for these conditions among family members in a study population in the Gambia, where strong community and family coherence are important determinants that have to be taken into consideration in promoting lifestyle changes. METHODS: We questioned 5389 adults as to any first-degree family history of major noncommunicable diseases (hypertension, obesity, diabetes and stroke), and measured their blood pressure (BP) and body mass index (BMI). Total blood cholesterol, triglyceride, uric acid, and creatinine concentrations were measured in a stratified subsample, as well as blood glucose (2 hours after ingesting 75 g glucose) in persons aged > or = 35 years. FINDINGS: A significant number of subjects reported a family history of hypertension (8.0%), obesity (5.4%), diabetes (3.3%) and stroke (1.4%), with 14.6% of participants reporting any of these NCDs. Subjects with a family history of hypertension had a higher diastolic BP and BMI, higher cholesterol and uric acid concentrations, and an increased risk of obesity. Those with a family history of obesity had a higher BMI and were at increased risk of obesity. Individuals with a family history of diabetes had a higher BMI and higher concentrations of glucose, cholesterol, triglycerides and uric acid, and their risk of obesity and diabetes was increased. Subjects with a family history of stroke had a higher BMI, as well as higher cholesterol, triglyceride and uric acid concentrations. CONCLUSIONS: A family history of hypertension, obesity, diabetes, or stroke was a significant risk factor for obesity and hyperlipidaemia. With increase of age, more pathological manifestations can develop in this high-risk group. Health professionals should therefore utilize every opportunity to include direct family members in health education. PMID:11357211

  12. The impact of obesity on prostate cancer recurrence observed after exclusion of diabetics

    PubMed Central

    Agalliu, Ilir; Williams, Steve; Adler, Brandon; Androga, Lagu; Siev, Michael; Lin, Juan; Xue, Xiaonan; Huang, Gloria; Strickler, Howard D.; Ghavamian, Reza

    2016-01-01

    Purpose Although overall there is a positive association between obesity and risk of prostate cancer (PrCa) recurrence, results of individual studies are somewhat inconsistent. We investigated whether the failure to exclude diabetics in prior studies could have increased the likelihood of conflicting results. Methods A total of 610 PrCa patients who underwent radical prostatectomy between 2005 and 2012 were followed for recurrence, defined as a rise in serum PSA ≥ 0.2 ng/ml following surgery. Body mass index (BMI) and history of type 2 diabetes were documented prior to PrCa surgery. The analysis was conducted using Cox proportional hazard models. Results Obesity (25.6 %) and diabetes (18.7 %) were common in this cohort. There were 87 (14.3 %) recurrence events during a median follow-up of 30.8 months after surgery among the 610 patients. When analyzed among all PrCa patients, no association was observed between BMI/obesity and PrCa recurrence. However, when analysis was limited to non-diabetics, obese men had a 2.27-fold increased risk (95 % CI 1.17–4.41) of PrCa recurrence relative to normal weight men, after adjusting for age and clinical/pathological tumor characteristics. Conclusions This study found a greater than twofold association between obesity/BMI and PrCa recurrence in non-diabetics. We anticipated these results because the relationship between BMI/obesity and the biologic factors that may underlie the PrCa recurrence–BMI/obesity association, such as insulin, may be altered by the use of anti-diabetes medication or diminished beta-cell insulin production in advanced diabetes. Studies to further assess the molecular factors that explain the BMI/obesity–PrCa recurrence relationship are warranted. PMID:25771797

  13. Cardiac abnormalities in youth with obesity and type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Childhood obesity has been linked to cardiovascular disease (CVD) risk in adulthood. Of great concern is the expected increase in the population's CVD burden in relation to childhood obesity. This is compounded by the risk related to chronic hyperglycemia exposure in youth with type 2 diabetes. We h...

  14. Obesity paradox in amputation risk among nonelderly diabetic men.

    PubMed

    Sohn, Min-Woong; Budiman-Mak, Elly; Oh, Elissa H; Park, Michael S; Stuck, Rodney M; Stone, Neil J; Pearce, William B

    2012-02-01

    The association between BMI and amputation risk is not currently well known. We used data for a cohort of diabetic patients treated in the US Department of Veterans Affairs Healthcare System in 2003. Men aged <65 years at the end of follow-up were examined for their amputation risk and amputation-free survival during the next 5 years (2004-2008). Compared to overweight individuals (BMI 25-29.9 kg/m(2)), the risks of amputation and treatment failure (amputation or death) were higher for patients with BMI <25 kg/m(2) and were lower for those with BMI ≥30 kg/m(2). Individuals with BMI ≥40 kg/m(2) were only half as likely to experience any (hazard ratios (HR) = 0.49; 95% confidence interval (CI), 0.30-0.80) and major amputations (HR = 0.53; 95% CI, 0.39-0.73) during follow-up as overweight individuals. While the amputation risk continued to decrease for higher BMI, amputation-free survival showed a slight upturn at BMI >40 kg/m(2). The association between obesity and amputation risk in our data shows a pattern consistent with "obesity paradox" observed in many health conditions. More research is needed to better understand pathophysiological mechanisms that may explain the paradoxical association between obesity and lower-extremity amputation (LEA) risk.

  15. Protein glycation, diabetes, and aging.

    PubMed

    Ulrich, P; Cerami, A

    2001-01-01

    Biological amines react with reducing sugars to form a complex family of rearranged and dehydrated covalent adducts that are often yellow-brown and/or fluorescent and include many cross-linked structures. Food chemists have long studied this process as a source of flavor, color, and texture changes in cooked, processed, and stored foods. During the 1970s and 1980s, it was realized that this process, called the Maillard reaction or advanced glycation, also occurs slowly in vivo. Advanced glycation endproducts (AGEs) that form are implicated, causing the complications of diabetes and aging, primarily via adventitious and crosslinking of proteins. Long-lived proteins such as structural collagen and lens crystallins particularly are implicated as pathogenic targets of AGE processes. AGE formation in vascular wall collagen appears to be an especially deleterious event, causing crosslinking of collagen molecules to each other and to circulating proteins. This leads to plaque formation, basement membrane thickening, and loss of vascular elasticity. The chemistry of these later-stage, glycation-derived crosslinks is still incompletely understood but, based on the hypothesis that AGE formation involves reactive carbonyl groups, the authors introduced the carbonyl reagent aminoguanidine hydrochloride as an inhibitor of AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers have shown the effectiveness of aminoguanidine in slowing or preventing a wide range of complications of diabetes and aging in animals and, recently, in humans. Since, the authors have developed a new class of agents, exemplified by 4,5-dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already-formed AGE protein-protein crosslinks. These agents are based on a new theory of AGE crosslinking that postulates that alpha-dicarbonyl structures are present in AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown to be capable of reverting

  16. Hepcidin and iron metabolism in non-diabetic obese and type 2 diabetic rats.

    PubMed

    Chen, Yue; Yin, Hui-qing; Liu, Hao-ling; Xiu, Lei; Peng, Xiao-yu

    2015-12-01

    The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups: control group, non-diabetic obese group and type 2 diabetic group (n=20 each). The rats were evaluated physiologically and biochemically. The hepatic histopathological changes were observed using haematoxylin and eosin (HE) staining. The mRNA expression patterns of hepcidin, interleukin-6 (IL-6), hypoxia-inducible factor (HIF) and ferroportin (Fpn) in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further analyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly (P<0.001). However, there was no significant difference in soluble transferring receptor (sTfR):ferritin ratio among the three groups (P>0.05). The real-time RT-PCR, immunohistochemistry and Western blotting results all revealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group (P<0.001). The expression levels of hepcidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant difference (P>0.05). However, the protein expression levels of hepcidin in type 2 diabetic group were significantly higher than those in non-diabetic obese group (P<0.05). Compared to control group, the expression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels of Fpn mRNA decreased (P<0.05). However, the expression levels of HIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is

  17. [Vitamin D, obesity, and diabetes:new technology toward drug development against metabolic diseases].

    PubMed

    Miyata, Yugo; Shimomura, Iichiro

    2016-03-01

    Obesity and diabetes are rapidly reaching epidemic proportions in many parts of world and are becoming one of the major public health problems. Many studies have been performed to develop treatments for obesity and diabetes. In clinical aspect, for example, vitamin D was assumed to be a causal factor of obesity and diabetes, and the effect of vitamin D supplementation on the patients was assessed. In addition to clinical study, basic researchers have tried to elucidate the mechanisms of obesity and diabetes. Recent studies show novel techniques for finding etiologic factors in obesity and diabetes. These effort will accelerate progress toward total eradication of obesity and diabetes.

  18. Analyzing the some biochemical parameters of diabetes mellitus and obese patients who applied to Siirt State Hospital endocrine polyclinic and their prevalence

    NASA Astrophysics Data System (ADS)

    Karageçili, Hasan; Yerlikaya, Emrah; Aydin, Ruken Zeynep

    2016-04-01

    Obesity and diabetes are major public health problems throughout the World. Obese individuals body mass index (BMI) is >30 kg/m2. Obesity is characterized by increased waist circumference, total body fat and hyperglycemia. The increased triglyceride and cholesterol level is also shown in obese individuals. The development of obesity is largely due to the consumption of high energy food and sedentary lifestyle. This study was held with the participation of patients applied to Siirt State Hospital endocrine policlinic for treatment. Our aim is to try to determine the biochemical relation and border line of obese and obese+diabetes mellitus patients. Patients and control group lipid profiles were studied in the hospital biochemisty laboratory. Laboratory results of diabetes+obese, obese and control groups were evaluated. Patients and control samples blood serum levels were compared according to their lipid profiles. In 2015, 735 diabetes mellitus type 2 patients applied to Endocrine polyclinic. Some of these patient's serum levels were evaluated. Difference between diabetes+obese and diabetes groups were near critical level for LDL and trigliserid. There were not observed statistically significant difference between groups in terms of HDL and cholesterol. There were found significant difference between groups for blood glucose p<0.003, age p<0.001. According to gender between women and men serum levels, ALT and AST levels; p<0.006 and cholesterol; p<0.04 were detected. According to participants education level blood biochemistry levels were observed statisticaly different p<0.001 with non-literacy group. In conclusion, obese and obese+diabetes patients blood serum values nearly close to each other. Obese subjects were been diabetic obese with age. In women obesity and diabetes mellitus prevalence were seen too much.

  19. Healthy lifestyles in Europe: prevention of obesity and type II diabetes by diet and physical activity.

    PubMed

    Astrup, A

    2001-04-01

    The prevalence of obesity is increasing rapidly in all age groups in most EU-countries and is one of the fastest growing epidemics, now affecting 10-40% of the adult population. Obesity increases the risk of serious co-morbidities such as type 2 diabetes, cardiovascular disease, certain cancers and reduced life expectancy, and these complications may account for 5-10% of all health costs in EU countries. The risk of diabetes is particularly increased by obesity, and 80-95% of the increase in diabetes can be attributed to obesity and overweight with abdominal fat distribution. There is robust evidence from cross-sectional and longitudinal studies to support that an energy-dense, high fat diet and physical inactivity are independent risk factors for weight gain and obesity. Furthermore, interaction between dietary fat and physical fitness determine fat balance, so that the obesity promoting effect of a high fat diet is enhanced in susceptible subjects, particularly in sedentary individuals with a genetic predisposition to obesity. Ad libitum consumption of diets low in fat and high in protein and complex carbohydrates, with a low glycaemic index, contributes to the prevention of weight gain in normal weight subjects. It also causes a spontaneous weight loss of 3-4 kg in overweight subjects, and has beneficial effects on risk factors for diabetes and CVD. To prevent obesity and diabetes there are grounds for recommending the combination of increasing daily physical activity level to a PAL-value of at least 1.8 and reducing dietary fat content to 20-25 energy-% in sedentary subjects, and to 25-35% in more physically active individuals.

  20. Lifestyle and genetics in obesity and type 2 diabetes.

    PubMed

    Temelkova-Kurktschiev, T; Stefanov, T

    2012-01-01

    Obesity and type 2 diabetes mellitus are multifactorial health threats caused by a complex interplay between genetic predisposition and the environment with dramatically increasing worldwide prevalence. The role of heritability in their etiology is well recognized, however, the numerous attempts made in order certain genetic variants determining individual susceptibility to be identified have had limited success, until recently. At present the advancements in human genetics and the utilization of the genome-wide association approach have led to the identification of over 20 genetic loci associated with, respectively obesity and type 2 diabetes. Most of the genes identified to date, however, have modest effect on disease risk suggesting that both diseases are unlikely to develop without the individual being exposed to obesity- and/or type 2 diabetes-promoting environment. Indeed, unhealthy lifestyle, characterized by physical inactivity and food overconsumption is an unequivocally established risk factor for obesity and type 2 diabetes. Numerous epidemiological studies and randomized controlled trials, on the other hand, have demonstrated that lifestyle modification is effective in obesity and type 2 diabetes prevention. Furthermore, gene-lifestyle interaction studies suggest that genetic susceptibility to obesity and type 2 diabetes may be partially or totally kept under control by healthy lifestyle or lifestyle modification and that lifestyle determines whether an individual is likely to develop the disease. Inherited factors, however, seem to influence individual response to a lifestyle intervention program and even the motivation for lifestyle change. Personalized interventions according to genotype may be, therefore, considered in the future. By then lifestyle modification targeting dietary change and increased physical activity may be recommended for successful obesity and type 2 diabetes prevention irrespectively of genetic susceptibility.

  1. Sugar Intake, Obesity, and Diabetes in India

    PubMed Central

    Gulati, Seema; Misra, Anoop

    2014-01-01

    Sugar and sweet consumption have been popular and intrinsic to Indian culture, traditions, and religion from ancient times. In this article, we review the data showing increasing sugar consumption in India, including traditional sources (jaggery and khandsari) and from sugar-sweetened beverages (SSBs). Along with decreasing physical activity, this increasing trend of per capita sugar consumption assumes significance in view of the high tendency for Indians to develop insulin resistance, abdominal adiposity, and hepatic steatosis, and the increasing “epidemic” of type 2 diabetes (T2DM) and cardiovascular diseases. Importantly, there are preliminary data to show that incidence of obesity and T2DM could be decreased by increasing taxation on SSBs. Other prevention strategies, encompassing multiple stakeholders (government, industry, and consumers), should target on decreasing sugar consumption in the Indian population. In this context, dietary guidelines for Indians show that sugar consumption should be less than 10% of total daily energy intake, but it is suggested that this limit be decreased. PMID:25533007

  2. Exercise in aging: its important role in mortality, obesity and insulin resistance

    PubMed Central

    Ryan, Alice S

    2011-01-01

    The prevalence of overweight and obesity has increased dramatically over the last several decades. Obesity and physical inactivity increase the risk for cardiovascular disease, Type 2 diabetes mellitus, hypertension, dyslipidemia and certain cancers. Obesity and low levels of physical fitness are also associated with increased risk of all-cause and cardiovascular mortality. Central and total obesity, insulin resistance and inactivity increase with age. Exercise training and increased fitness promote positive changes in body composition and improve insulin sensitivity. This article will describe the effects of exercise training, both aerobic and resistive, on body composition and obesity as well as review studies investigating the effects of exercise training on glucose metabolism and insulin sensitivity in older adults. Adopting a physically active lifestyle should be emphasized in overweight and obese individuals with insulin resistance to reduce the risk for cardiovascular events in the aging population. PMID:21359160

  3. Association between Nutrient Intake and Obesity in Type 2 Diabetic Patients from the Korean National Diabetes Program: A Cross-Sectional Study

    PubMed Central

    Kim, So Hun; Hong, Seong Bin; Suh, Young Ju; Choi, Yun Jin; Lee, Hyoung Woo; Park, Ie Byung; Chon, Suk; Woo, Jeong-Taek; Baik, Sei Hyun; Park, Yongsoo; Kim, Dae Jung; Lee, Kwan Woo; Kim, Young Seol

    2012-01-01

    The aim of the study was to assess the association between usual dietary nutrient intake and obesity in Korean type 2 diabetic patients. We examined 2,832 type 2 diabetic patients from the Korean National Diabetes Program cohort who completed dietary assessment and clinical evaluation in this cross-sectional study. In men, higher dietary fiber intake was associated with a lower odds of being obese (Ptrend = 0.003) and in women, higher protein intake was associated with a lower odds of being obese (Ptrend = 0.03) after adjustment for age, diabetes duration, HbA1c, alcohol drinking, income, education level, and calorie intake. In men, higher fiber intake was associated with lower odds of obesity after further adjustment for diastolic blood pressure, physical activity, and possible confounding nutritional intake and medication. The multivariable adjusted odds ratio for the highest quintile of fiber intake was 0.37 (Ptrend < 0.001). In women, protein intake was not associated with obesity after further adjustment. In conclusion, higher intake of dietary fiber is associated with lower odds of being obese in type 2 diabetic men, suggesting a role for dietary fiber in the management and prevention of obesity in type 2 diabetes (ClinicalTrials.gov: NCT 01212198). PMID:23091316

  4. Impact of hypertension, overall obesity and abdominal obesity on diabetes incidence in Shanghai residents with different glucose levels.

    PubMed

    Qian, Qiaohui; Li, Xu; Feng, Bo

    2012-06-01

    The impact of hypertension, overall obesity and abdominal obesity, individually or collectively, on diabetes incidence over a period of 5 years in residents with different glucose levels is diverse, with abdominal obesity having an impact in both non-diabetic hyperglycaemia and normal groups.

  5. (Pre)diabetes, brain aging, and cognition.

    PubMed

    S Roriz-Filho, Jarbas; Sá-Roriz, Ticiana M; Rosset, Idiane; Camozzato, Ana L; Santos, Antonio C; Chaves, Márcia L F; Moriguti, Júlio César; Roriz-Cruz, Matheus

    2009-05-01

    Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of diabetes mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain. How can clinical hyperinsulinism be a risk factor for AD whereas lab experiments evidence insulin to be an important neurothrophic factor? These two apparent paradoxal findings may be reconciliated by evoking the concept of insulin resistance. Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE). Since IDE is much more selective for insulin than for Abeta, brain hyperinsulinism may deprive Abeta of its main clearance mechanism. Hyperglycemia and hyperinsulinemia seems to accelerate brain aging also by inducing tau hyperphosphorylation and amyloid oligomerization, as well as by leading to widespread brain microangiopathy

  6. Associations between lower extremity muscle mass and metabolic parameters related to obesity in Japanese obese patients with type 2 diabetes.

    PubMed

    Hamasaki, Hidetaka; Kawashima, Yu; Adachi, Hiroki; Moriyama, Sumie; Katsuyama, Hisayuki; Sako, Akahito; Yanai, Hidekatsu

    2015-01-01

    Background. Age-related loss of muscle mass (sarcopenia) increases the incidence of obesity in the elderly by reducing physical activity. This sarcopenic obesity may become self-perpetuating, increasing the risks for metabolic syndrome, disability, and mortality. We investigated the associations of two sarcopenic indices, the ratio of lower extremity muscle mass to body weight (L/W ratio) and the ratio of lower extremity muscle mass to upper extremity muscle mass (L/U ratio), with metabolic parameters related to obesity in patients with type 2 diabetes and obesity. Methods. Of 148 inpatients with type 2 diabetes treated between October 2013 and April 2014, we recruited 26 with obesity but no physical disability. Daily physical activity was measured by a triaxial accelerometer during a period of hospitalization, and which was also evaluated by our previously reported non-exercise activity thermogenesis questionnaire. We measured body composition by bioelectrical impedance and investigated the correlations of L/W and L/U ratios with body weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), visceral fat area, subcutaneous fat area, serum lipid profile, and daily physical activity. Results. The L/W ratio was significantly and negatively correlated with BMI, WC, WHR, body fat mass, body fat percentage, subcutaneous fat area, and serum free fatty acid concentration, was positively correlated with daily physical activity: the locomotive non-exercise activity thermogenesis score, but was not correlated with visceral fat area. The L/U ratio was significantly and positively correlated with serum high-density lipoprotein cholesterol. Conclusions. High L/W and L/U ratios, indicative of relatively preserved lower extremity muscle mass, were predictive of improved metabolic parameters related to obesity. Preserved muscle fitness in obesity, especially of the lower extremities, may prevent sarcopenic obesity and lower associated risks for metabolic

  7. Obesity accelerates epigenetic aging of human liver.

    PubMed

    Horvath, Steve; Erhart, Wiebke; Brosch, Mario; Ammerpohl, Ole; von Schönfels, Witigo; Ahrens, Markus; Heits, Nils; Bell, Jordana T; Tsai, Pei-Chien; Spector, Tim D; Deloukas, Panos; Siebert, Reiner; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Schafmayer, Clemens; Hampe, Jochen

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer. PMID:25313081

  8. Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer

    PubMed Central

    Polvani, Simone; Tarocchi, Mirko; Tempesti, Sara; Bencini, Lapo; Galli, Andrea

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks (sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ (PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stress-associated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients. PMID:26937133

  9. Approach to the Obese Adolescent with New-Onset Diabetes

    PubMed Central

    Zeitler, Philip

    2010-01-01

    The prevalence of both type 1 and type 2 diabetes among children and adolescents has been steadily increasing over the last few decades. However, as the general pediatric population becomes more obese and more ethnically diverse, reliance on phenotypic characteristics for distinguishing between these types of diabetes is becoming increasingly untenable. Yet, the recognition of differences in treatment strategies, associated disorders, and both short- and long-term diabetes and cardiovascular outcomes supports the importance of diagnostic efforts to make a distinction between diabetes types. An approach to determination of diabetes type is discussed, focused on the presence or absence of autoimmunity and assessment of β-cell function. At the time of diagnosis, it is generally not possible to be certain of diabetes type, and therefore, initial treatment decisions must be made based on aspects of the presenting physiology, with adjustments in treatment approach made as the individual’s course proceeds and additional information becomes available. The apparent overlap between type 1 and type 2 diabetes that occurs in obese adolescents has resulted in some controversy regarding mixed forms of diabetes that are ultimately semantic, but this does raise interesting questions about the treatment of type 1 diabetes in the presence of an insulin-resistant phenotype. Finally, the lack of information about the efficacy of treatment of cardiovascular risk factors, such as dyslipidemia and hypertension, along with the well-documented challenges in adherence to chronic illness treatment in this population, creates substantial challenges. PMID:21131537

  10. How effective are antioxidant supplements in obesity and diabetes?

    PubMed

    Abdali, Daniyal; Samson, Sue E; Grover, Ashok Kumar

    2015-01-01

    Obesity is a central health issue due to its epidemic prevalence and its association with type 2 diabetes and other comorbidities. Obesity is not just being overweight. It is a metabolic disorder due to the accumulation of excess dietary calories into visceral fat and the release of high concentrations of free fatty acids into various organs. It represents a state of chronic oxidative stress and low-grade inflammation whose intermediary molecules may include leptin, adiponectin and cytokines. It may progress to hyperglycemia, leading to type 2 diabetes. Whether or not dietary antioxidant supplements are useful in the management of obesity and type 2 diabetes is discussed in this review. Only the benefits for obesity and diabetes are examined here. Other health benefits of antioxidants are not considered. There are difficulties in comparing studies in this field because they differ in the time frame, participants' ethnicity, administration of antioxidant supplements, and even in how obesity was measured. However, the literature presents reasonable evidence for marginal benefits of supplementation with zinc, lipoic acid, carnitine, cinnamon, green tea, and possibly vitamin C plus E, although the evidence is much weaker for omega-3 polyunsaturated fatty acids, coenzyme Q10, green coffee, resveratrol, or lycopene. Overall, antioxidant supplements are not a panacea to compensate for a fast-food and video-game way of living, but antioxidant-rich foods are recommended as part of the lifestyle. Such antioxidant foods are commonly available. PMID:25791371

  11. Dysfunction of human subcutaneous fat arterioles in obesity alone or obesity associated with Type 2 diabetes.

    PubMed

    Georgescu, Adriana; Popov, Doina; Constantin, Anamaria; Nemecz, Miruna; Alexandru, Nicoleta; Cochior, Daniel; Tudor, Aura

    2011-05-01

    The aim of the present study was to examine the effects of obesity alone and obesity associated with Type 2 diabetes on the structure, vascular reactivity and response to insulin of isolated human subcutaneous fat arterioles; these effects were correlated with the expression of insulin signalling proteins. Periumbilical subcutaneous adipose tissue was explanted during surgery, small arterioles (internal diameter 220 ± 40 μm) were dissected out and investigated by electron microscopy, myography and immunoblotting. Compared with the subcutaneous arterioles of lean subjects, obesity activated the endothelium, enhanced the accumulation of collagen within vascular wall and increased the sensitivity of adrenergic response; obesity also diminished eNOS (endothelial NO synthase) protein expression, NO production, and endothelium-dependent and insulin-induced vasodilatation, as well as the protein expression of both IRS (insulin receptor substrates)-1 and IRS-2 and of the downstream molecules in the insulin signalling pathway, such as PI3K (phosphoinositide 3-kinase), phospho-Akt and Akt. When obesity was associated with Type 2 diabetes, these changes were significantly augmented. In conclusion, obesity alone or obesity associated with Type 2 diabetes alters human periumbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3K and Akt in the insulin signalling pathway. PMID:20979575

  12. Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes.

    PubMed

    Lin, Eugene; Pei, Dee; Huang, Yi-Jen; Hsieh, Chang-Hsun; Wu, Lawrence Shih-Hsin

    2009-08-01

    Recent studies indicate that obesity may play a key role in modulating genetic predispositions to type 2 diabetes (T2D). This study examines the main effects of both single-locus and multilocus interactions among genetic variants in Taiwanese obese and nonobese individuals to test the hypothesis that obesity-related genes may contribute to the etiology of T2D independently and/or through such complex interactions. We genotyped 11 single nucleotide polymorphisms for 10 obesity candidate genes including adrenergic beta-2-receptor surface, adrenergic beta-3-receptor surface, angiotensinogen, fat mass and obesity associated gene, guanine nucleotide binding protein beta polypeptide 3 (GNB3), interleukin 6 receptor, proprotein convertase subtilisin/kexin type 1 (PCSK1), uncoupling protein 1, uncoupling protein 2, and uncoupling protein 3. There were 389 patients diagnosed with T2D and 186 age- and sex-matched controls. Single-locus analyses showed significant main effects of the GNB3 and PCSK1 genes on the risk of T2D among the nonobese group (p = 0.002 and 0.047, respectively). Further, interactions involving GNB3 and PCSK1 were suggested among the nonobese population using the generalized multifactor dimensionality reduction method (p = 0.001). In addition, interactions among angiotensinogen, fat mass and obesity associated gene, GNB3, and uncoupling protein 3 genes were found in a significant four-locus generalized multifactor dimensionality reduction model among the obese population (p = 0.001). The results suggest that the single nucleotide polymorphisms from the obesity candidate genes may contribute to the risk of T2D independently and/or in an interactive manner according to the presence or absence of obesity.

  13. Bariatric Surgery for People with Diabetes and Morbid Obesity

    PubMed Central

    2009-01-01

    Executive Summary In June 2008, the Medical Advisory Secretariat began work on the Diabetes Strategy Evidence Project, an evidence-based review of the literature surrounding strategies for successful management and treatment of diabetes. This project came about when the Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the Ministry’s newly released Diabetes Strategy. After an initial review of the strategy and consultation with experts, the secretariat identified five key areas in which evidence was needed. Evidence-based analyses have been prepared for each of these five areas: insulin pumps, behavioural interventions, bariatric surgery, home telemonitoring, and community based care. For each area, an economic analysis was completed where appropriate and is described in a separate report. To review these titles within the Diabetes Strategy Evidence series, please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/masabout.html, Diabetes Strategy Evidence Platform: Summary of Evidence-Based Analyses Continuous Subcutaneous Insulin Infusion Pumps for Type 1 and Type 2 Adult Diabetics: An Evidence-Based Analysis Behavioural Interventions for Type 2 Diabetes: An Evidence-Based Analysis Bariatric Surgery for People with Diabetes and Morbid Obesity: An Evidence-Based Summary Community-Based Care for the Management of Type 2 Diabetes: An Evidence-Based Analysis Home Telemonitoring for Type 2 Diabetes: An Evidence-Based Analysis Application of the Ontario Diabetes Economic Model (ODEM) to Determine the Cost-effectiveness and Budget Impact of Selected Type 2 Diabetes Interventions in Ontario Objective The purpose of this evidence-based analysis was to examine the effectiveness and cost-effectiveness of bariatric surgery for the management of diabetes in morbidly obese people. This report summarized evidence specific

  14. Ending SNAP subsidies for sugar-sweetened beverages could reduce obesity and type 2 diabetes.

    PubMed

    Basu, Sanjay; Seligman, Hilary Kessler; Gardner, Christopher; Bhattacharya, Jay

    2014-06-01

    To reduce obesity and type 2 diabetes rates, lawmakers have proposed modifying Supplemental Nutrition Assistance Program (SNAP) benefits to encourage healthier food choices. We examined the impact of two proposed policies: a ban on using SNAP dollars to buy sugar-sweetened beverages; and a subsidy in which for every SNAP dollar spent on fruit and vegetables, thirty cents is credited back to participants' SNAP benefit cards. We used nationally representative data and models describing obesity, type 2 diabetes, and determinants of food consumption among a sample of over 19,000 SNAP participants. We found that a ban on SNAP purchases of sugar-sweetened beverages would be expected to significantly reduce obesity prevalence and type 2 diabetes incidence, particularly among adults ages 18-65 and some racial and ethnic minorities. The subsidy policy would not be expected to have a significant effect on obesity and type 2 diabetes, given available data. Such a subsidy could, however, more than double the proportion of SNAP participants who meet federal vegetable and fruit consumption guidelines.

  15. Lean diabetes mellitus: An emerging entity in the era of obesity.

    PubMed

    George, Amrutha Mary; Jacob, Amith George; Fogelfeld, Leon

    2015-05-15

    Much has been published on the characteristics of type 2 diabetes mellitus and its association with the epidemic of obesity. But relatively little is known about the incidence of lean diabetes, progression of disease and fate of the patients with low-normal body mass index (< 25). Studies in developing countries have shown that the clinical characteristics of these patients include history of childhood malnutrition, poor socioeconomic status, relatively early age of onset and absence of ketosis on withdrawal of insulin. In the United States, recent studies showed that the lean, normal weight diabetes is not rare especially among minority populations. They showed that these patients are mainly males, have higher prevalence of insulin use indicating rapid beta cell failure. They might have increased total, cardiovascular and non cardiovascular mortality when compared to obese diabetic patients. In this review, the epidemiologic and clinical features of lean diabetes are presented. The potential causal mechanisms of this emerging diabetes type that may include genetic, autoimmune, acquired and behavioral factors are discussed. The need for studies to further elucidate the causation as well as specific prevention and treatment of lean diabetes is emphasized. PMID:25987958

  16. [Type 2 diabetes, obesity and nutrition, a paradigm shift].

    PubMed

    Bourcelot, Emilie; Combes, Jérôme

    2016-05-01

    Obesity and type 2 diabetes are two complex and multifactorial chronic diseases. Nutritional management is based on an educational and bio-psycho-sensory approach centred on the patient using cognitive-behavioural and emotionally-focused therapy tools. PMID:27157552

  17. Ayurvedic concept of obesity, metabolic syndrome, and diabetes mellitus.

    PubMed

    Sharma, Hari; Chandola, H M

    2011-06-01

    Obesity, metabolic syndrome, and diabetes mellitus are increasing to epidemic proportions globally. There are 400 million clinically obese adults worldwide and there are more than 220 million people who have diabetes. The global impact of these disorders is immense in terms of human suffering and economic burden. There is an urgent need for a more effective understanding of these disease processes and their management, including the use of natural strategies that are affordable and efficacious. The health care system known as Ayurveda has much to offer in this regard. Ayurveda describes a set of complex clinical disorders, collectively called Prameha, that are characterized by frequent abnormal micturition. The clinical conditions associated with Prameha correlate in many ways with obesity, metabolic syndrome, and diabetes mellitus. The etiology, classification, pathogenesis, and management of Prameha are discussed at length and in detail in the Ayurvedic texts. The theoretical background and comprehensive set of strategies Ayurveda utilizes to treat Prameha may be valuable in managing obesity, metabolic syndrome, and diabetes mellitus in an efficacious and cost-effective manner. PMID:21649521

  18. Epigenetics in adipose tissue, obesity, weight loss and diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Given the role that the diet and other environmental factors play in the development of obesity and type 2 diabetes, the implication of different epigenetic processes is being investigated. Although it is well known that the environmental factors can cause cell type-dependent epigenetic changes, inc...

  19. Alterations in white matter volume and integrity in obesity and type 2 diabetes.

    PubMed

    van Bloemendaal, Liselotte; Ijzerman, Richard G; Ten Kulve, Jennifer S; Barkhof, Frederik; Diamant, Michaela; Veltman, Dick J; van Duinkerken, Eelco

    2016-06-01

    Type 2 diabetes mellitus (T2DM) is characterized by obesity, hyperglycemia and insulin resistance. Both T2DM and obesity are associated with cerebral complications, including an increased risk of cognitive impairment and dementia, however the underlying mechanisms are largely unknown. In the current study, we aimed to determine the relative contributions of obesity and the presence of T2DM to altered white matter structure. We used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to measure white matter integrity and volume in obese T2DM patients without micro- or macrovascular complications, age- gender- and BMI-matched normoglycemic obese subjects and age- and gender-matched normoglycemic lean subjects. We found that obese T2DM patients compared with lean subjects had lower axial diffusivity (in the right corticospinal tract, right inferior fronto-occipital tract, right superior longitudinal fasciculus and right forceps major) and reduced white matter volume (in the right inferior parietal lobe and the left external capsule region). In normoglycemic obese compared with lean subjects axial diffusivity as well as white matter volume tended to be reduced, whereas there were no significant differences between normoglycemic obese subjects and T2DM patients. Decreased white matter integrity and volume were univariately related to higher age, being male, higher BMI, HbA1C and fasting glucose and insulin levels. However, multivariate analyses demonstrated that only BMI was independently related to white matter integrity, and age, gender and BMI to white matter volume loss. Our data indicate that obese T2DM patients have reduced white matter integrity and volume, but that this is largely explained by BMI, rather than T2DM per se.

  20. Myotubes from Severely Obese Type 2 Diabetic Subjects Accumulate Less Lipids and Show Higher Lipolytic Rate than Myotubes from Severely Obese Non-Diabetic Subjects

    PubMed Central

    Bakke, Siril S.; Kase, Eili T.; Moro, Cedric; Stensrud, Camilla; Damlien, Lisbeth; Ludahl, Marianne O.; Sandbu, Rune; Solheim, Brita Marie; Rustan, Arild C.; Hjelmesæth, Jøran; Thoresen, G. Hege; Aas, Vigdis

    2015-01-01

    About 80% of patients with type 2 diabetes are classified as overweight. However, only about 1/3 of severely obese subjects have type 2 diabetes. This indicates that several severely obese individuals may possess certain characteristics that protect them against type 2 diabetes. We therefore hypothesized that this apparent paradox could be related to fundamental differences in skeletal muscle lipid handling. Energy metabolism and metabolic flexibility were examined in human myotubes derived from severely obese subjects without (BMI 44±7 kg/m2) and with type 2 diabetes (BMI 43±6 kg/m2). Lower insulin sensitivity was observed in myotubes from severely obese subjects with type 2 diabetes. Lipolysis rate was higher, and oleic acid accumulation, triacylglycerol content, and fatty acid adaptability were lower in myotubes from severely obese subjects with type 2 diabetes compared to severely obese non-diabetic subjects. There were no differences in lipid distribution and mRNA and protein expression of the lipases HSL and ATGL, the lipase cofactor CGI-58, or the lipid droplet proteins PLIN2 and PLIN3. Glucose and oleic acid oxidation were also similar in cells from the two groups. In conclusion, myotubes established from severely obese donors with established type 2 diabetes had lower ability for lipid accumulation and higher lipolysis rate than myotubes from severely obese donors without diabetes. This indicates that a difference in intramyocellular lipid turnover might be fundamental in evolving type 2 diabetes. PMID:25790476

  1. Obesity and type 2 diabetes in children: epidemiology and treatment.

    PubMed

    Pulgaron, Elizabeth R; Delamater, Alan M

    2014-08-01

    The incidence of overweight and obesity among children has increased dramatically in recent decades, with about one-third of children in the U.S. currently being either overweight or obese. Being overweight in early childhood increases risk for later obesity. There is evidence for the efficacy of family-based behavioral treatment to control weight and improve health outcomes. Obesity-related health risks have been documented, including metabolic syndrome. There is also increasing incidence of type 2 diabetes (T2D) among youth in recent years, with obesity and family history of T2D generally present. Lower income and ethnic minority status are associated with both obesity and T2D in youth. Most youth with T2D do not achieve optimal glycemic control, and are at high risk for later health complications. Obesity and T2D represent significant public health issues with potentially great personal and societal cost. Research addressing the prevention of obesity and T2D among youth is urgently needed.

  2. Obesity and Type 2 Diabetes in Children: Epidemiology and Treatment

    PubMed Central

    Pulgaron, Elizabeth R.; Delamater, Alan M.

    2014-01-01

    The incidence of overweight and obesity among children has increased dramatically in recent decades, with about one-third of children in the U.S. currently being either overweight or obese. Being overweight in early childhood increases risk for later obesity. There is evidence for the efficacy of family-based behavioral treatment to control weight and improve health outcomes. Obesity-related health risks have been documented, including metabolic syndrome. There is also increasing incidence of type 2 diabetes (T2D) among youth in recent years, with obesity and family history of T2D generally present. Lower income and ethnic minority status are associated with both obesity and T2D in youth. Most youth with T2D do not achieve optimal glycemic control, and are at high risk for later health complications. Obesity and T2D represent significant public health issues with potentially great personal and societal cost. Research addressing the prevention of obesity and T2D among youth is urgently needed. PMID:24919749

  3. Inflammation in Maternal Obesity and Gestational Diabetes Mellitus

    PubMed Central

    Pantham, Priyadarshini; Aye, Irving L. M. H; Powell, Theresa L.

    2015-01-01

    The prevalence of maternal obesity is rising rapidly worldwide and constitutes a major obstetric problem, increasing mortality and morbidity in both mother and offspring. Obese women are predisposed to pregnancy complications such as gestational diabetes mellitus (GDM), and children of obese mothers are more likely to develop cardiovascular and metabolic disease in later life. Maternal obesity and GDM may be associated with a state of chronic, low-grade inflammation termed “metainflammation”, as opposed to an acute inflammatory response. This inflammatory environment may be one mechanism by which offspring of obese women are programmed to develop adult disorders. Herein we review the evidence that maternal obesity and GDM are associated with changes in the maternal, fetal and placental inflammatory profile. Maternal inflammation in obesity and GDM may not always be associated with fetal inflammation. We propose that the placenta ‘senses’ and adapts to the maternal inflammatory environment, and plays a central role as both a target and producer of inflammatory mediators. In this manner, maternal obesity and GDM may indirectly program the fetus for later disease by influencing placental function. PMID:25972077

  4. Differences in emotional distress among inpatients with type 1, obese type 2, and non-obese type 2 diabetes mellitus.

    PubMed

    Miyawaki, Yoshiko; Iwahashi, Hiromi; Okauchi, Yukiyoshi; Sudo, Yoshiko; Fujiwara, Yuko; Omote, Yayoko; Imagawa, Akihisa; Shimomura, Iichiro

    2015-01-01

    Objective The purpose of this study was to determine the differences in emotional distress among three groups of inpatients with type 1, obese type 2, and non-obese type 2 diabetes during hospitalization. Methods The 42 participating inpatients were divided into three groups: type 1 diabetes (n=11), obese type 2 diabetes [body mass index (BMI) ≥25 kg/m(2); n=24], and non-obese type 2 diabetes (BMI <25 kg/m(2); n=7). The Problem Areas in Diabetes (PAID) scale, which is a self-administered questionnaire to assess emotional distress in the patients with diabetes, was performed at admission and discharge. Results The total PAID score was similar and tended to improve during hospitalization in all three groups, although there were differences among the groups in the scores of particular questions. At admission, the score of the question "worrying about low blood sugar reactions?" was significantly different among the three groups and highest in the patients with type 1 diabetes. At discharge, the score of "not accepting diabetes?" was significantly different among the three groups and highest in the patients with non-obese type 2 diabetes, while that of "feeling unsatisfied with your diabetes physician?" was significantly different among the three groups and highest in the patients with obese type 2 diabetes. The score of "feelings of deprivation regarding food and meals?" significantly worsened in the patients with obese type 2 diabetes during hospitalization compared with the patients in with non-obese type 2 diabetes. Conclusion The characteristics of emotional distress during hospitalization varied among the patients with the three types of diabetes, thus emphasizing the importance of tailoring support according to the type of diabetes.

  5. Differences in emotional distress among inpatients with type 1, obese type 2, and non-obese type 2 diabetes mellitus.

    PubMed

    Miyawaki, Yoshiko; Iwahashi, Hiromi; Okauchi, Yukiyoshi; Sudo, Yoshiko; Fujiwara, Yuko; Omote, Yayoko; Imagawa, Akihisa; Shimomura, Iichiro

    2015-01-01

    Objective The purpose of this study was to determine the differences in emotional distress among three groups of inpatients with type 1, obese type 2, and non-obese type 2 diabetes during hospitalization. Methods The 42 participating inpatients were divided into three groups: type 1 diabetes (n=11), obese type 2 diabetes [body mass index (BMI) ≥25 kg/m(2); n=24], and non-obese type 2 diabetes (BMI <25 kg/m(2); n=7). The Problem Areas in Diabetes (PAID) scale, which is a self-administered questionnaire to assess emotional distress in the patients with diabetes, was performed at admission and discharge. Results The total PAID score was similar and tended to improve during hospitalization in all three groups, although there were differences among the groups in the scores of particular questions. At admission, the score of the question "worrying about low blood sugar reactions?" was significantly different among the three groups and highest in the patients with type 1 diabetes. At discharge, the score of "not accepting diabetes?" was significantly different among the three groups and highest in the patients with non-obese type 2 diabetes, while that of "feeling unsatisfied with your diabetes physician?" was significantly different among the three groups and highest in the patients with obese type 2 diabetes. The score of "feelings of deprivation regarding food and meals?" significantly worsened in the patients with obese type 2 diabetes during hospitalization compared with the patients in with non-obese type 2 diabetes. Conclusion The characteristics of emotional distress during hospitalization varied among the patients with the three types of diabetes, thus emphasizing the importance of tailoring support according to the type of diabetes. PMID:26466689

  6. Obesity, diabetes, and length of time in the United States

    PubMed Central

    Tsujimoto, Tetsuro; Kajio, Hiroshi; Sugiyama, Takehiro

    2016-01-01

    Abstract Obesity prevalence remains high in the United States (US), and is rising in most other countries. This is a repeated cross-sectional study using a nationally representative sample of the National Health and Nutrition Examination Survey 1999 to 2012. Multivariate logistic regression analyses were separately performed for adults (n = 37,639) and children/adolescents (n = 28,282) to assess the associations between the length of time in the US, and the prevalences of obesity and diabetes. In foreign-born adults, the prevalences of both obesity and diabetes increased with the length of time in the US, and ≥20 years in the US was associated with significantly higher rates of obesity (adjusted odds ratio [aOR] 2.32, 95% confidence interval [CI] 1.22–4.40, P = 0.01) and diabetes (aOR 4.22, 95% CI 1.04–17.08, P = 0.04) compared with <1 year in the US. In children/adolescents, obesity prevalence was significantly higher in those born in the US than those who had been in the US for <1 year (aOR 3.15, 95% CI 1.51–6.56, P = 0.002). When analyzed by year, obesity prevalence was significantly higher in US-born than in foreign-born adults from 1999 to 2012. On the other hand, the gap in obesity prevalence between US-born and foreign-born children/adolescents decreased from 1999 to 2011 due to a rapid increase in obesity prevalence among the foreign-born population, until there was no significant difference in 2011 to 2012. This study revealed that the risks of obesity and diabetes have increased in foreign-born US residents with time living in the US. However, the obesity gap between US-born and foreign-born populations is closing. PMID:27583867

  7. Obesity prevalence among low-income, preschool-aged children - United States, 1998-2008.

    PubMed

    2009-07-24

    Childhood obesity continues to be a leading public health concern that disproportionately affects low-income and minority children. Children who are obese in their preschool years are more likely to be obese in adolescence and adulthood and to develop diabetes, hypertension, hyperlipidemia, asthma, and sleep apnea. One of the Healthy People 2010 objectives (19-3) is to reduce to 5% the proportion of children and adolescents who are obese. CDC's Pediatric Nutrition Surveillance System (PedNSS) is the only source of nationally compiled obesity surveillance data obtained at the state and local level for low-income, preschool-aged children participating in federally funded health and nutrition programs. To describe progress in reducing childhood obesity, CDC examined trends and current prevalence in obesity using PedNSS data submitted by participating states, territories, and Indian tribal organizations during 1998-2008. The findings indicated that obesity prevalence among low-income, preschool-aged children increased steadily from 12.4% in 1998 to 14.5% in 2003, but subsequently remained essentially the same, with a 14.6% prevalence in 2008. Reducing childhood obesity will require effective prevention strategies that focus on environments and policies promoting physical activity and a healthy diet for families, child care centers, and communities.

  8. Diabetes burden in Brazil: fraction attributable to overweight, obesity, and excess weight.

    PubMed

    Flor, Luísa Sorio; Campos, Monica Rodrigues; Oliveira, Andreia Ferreira de; Schramm, Joyce Mendes de Andrade

    2015-01-01

    OBJECTIVE To estimate the burden of type 2 diabetes mellitus and its percentage attributable to overweight and obesity in Brazil. METHODS The burden of diabetes mellitus was described in terms of disability-adjusted life years, which is the sum of two components: years of life lost and years lived with disability. To calculate the fraction of diabetes mellitus attributable to overweight, obesity, and excess weight, we used the prevalence of these risk factors according to sex and age groups (> 20 years) obtained from the 2008 Pesquisa Dimensões Sociais das Desigualdades (Social Dimensions of Inequality Survey) and the relative risks derived from the international literature. RESULTS Diabetes mellitus accounted for 5.4% of Brazilian disability-adjusted life years in 2008, with the largest fraction attributed to the morbidity component (years lived with disability). Women exhibited higher values for disability-adjusted life years. In Brazil, 49.2%, 58.3%, and 70.6% of diabetes mellitus in women was attributable to overweight, obesity, and excess weight, respectively. Among men, these percentages were 40.5%, 45.4%, and 60.3%, respectively. Differences were observed with respect to Brazilian regions and age groups. CONCLUSIONS A large fraction of diabetes mellitus was attributable to preventable individual risk factors and, in about six years, the contribution of these factors significant increased, particularly among men. Policies aimed at promoting healthy lifestyle habits, such as a balanced diet and physical activity, can have a significant impact on reducing the burden of diabetes mellitus in Brazil. PMID:26018787

  9. Diabetes burden in Brazil: fraction attributable to overweight, obesity, and excess weight

    PubMed Central

    Flor, Luísa Sorio; Campos, Monica Rodrigues; de Oliveira, Andreia Ferreira; Schramm, Joyce Mendes de Andrade

    2015-01-01

    OBJECTIVE To estimate the burden of type 2 diabetes mellitus and its percentage attributable to overweight and obesity in Brazil. METHODS The burden of diabetes mellitus was described in terms of disability-adjusted life years, which is the sum of two components: years of life lost and years lived with disability. To calculate the fraction of diabetes mellitus attributable to overweight, obesity, and excess weight, we used the prevalence of these risk factors according to sex and age groups (> 20 years) obtained from the 2008 Pesquisa Dimensões Sociais das Desigualdades (Social Dimensions of Inequality Survey) and the relative risks derived from the international literature. RESULTS Diabetes mellitus accounted for 5.4% of Brazilian disability-adjusted life years in 2008, with the largest fraction attributed to the morbidity component (years lived with disability). Women exhibited higher values for disability-adjusted life years. In Brazil, 49.2%, 58.3%, and 70.6% of diabetes mellitus in women was attributable to overweight, obesity, and excess weight, respectively. Among men, these percentages were 40.5%, 45.4%, and 60.3%, respectively. Differences were observed with respect to Brazilian regions and age groups. CONCLUSIONS A large fraction of diabetes mellitus was attributable to preventable individual risk factors and, in about six years, the contribution of these factors significant increased, particularly among men. Policies aimed at promoting healthy lifestyle habits, such as a balanced diet and physical activity, can have a significant impact on reducing the burden of diabetes mellitus in Brazil. PMID:26018787

  10. Diabetes burden in Brazil: fraction attributable to overweight, obesity, and excess weight.

    PubMed

    Flor, Luísa Sorio; Campos, Monica Rodrigues; Oliveira, Andreia Ferreira de; Schramm, Joyce Mendes de Andrade

    2015-01-01

    OBJECTIVE To estimate the burden of type 2 diabetes mellitus and its percentage attributable to overweight and obesity in Brazil. METHODS The burden of diabetes mellitus was described in terms of disability-adjusted life years, which is the sum of two components: years of life lost and years lived with disability. To calculate the fraction of diabetes mellitus attributable to overweight, obesity, and excess weight, we used the prevalence of these risk factors according to sex and age groups (> 20 years) obtained from the 2008 Pesquisa Dimensões Sociais das Desigualdades (Social Dimensions of Inequality Survey) and the relative risks derived from the international literature. RESULTS Diabetes mellitus accounted for 5.4% of Brazilian disability-adjusted life years in 2008, with the largest fraction attributed to the morbidity component (years lived with disability). Women exhibited higher values for disability-adjusted life years. In Brazil, 49.2%, 58.3%, and 70.6% of diabetes mellitus in women was attributable to overweight, obesity, and excess weight, respectively. Among men, these percentages were 40.5%, 45.4%, and 60.3%, respectively. Differences were observed with respect to Brazilian regions and age groups. CONCLUSIONS A large fraction of diabetes mellitus was attributable to preventable individual risk factors and, in about six years, the contribution of these factors significant increased, particularly among men. Policies aimed at promoting healthy lifestyle habits, such as a balanced diet and physical activity, can have a significant impact on reducing the burden of diabetes mellitus in Brazil.

  11. Treating Diabetes and Prediabetes by Focusing on Obesity Management

    PubMed Central

    Khaodhiar, Lalita; Cummings, Sue; Apovian, Caroline M.

    2010-01-01

    Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In obesity, the adipose cell releases non-esterified free fatty acids, hormones, adipocytokines, and other substances that are involved in insulin resistance. Under normal conditions, the pancreatic islet β cells increase production of insulin sufficiently to maintain normal blood glucose concentrations despite insulin resistance. However, in genetically predisposed patients, the β cells eventually become dysfunctional and T2DM develops. The development of T2DM can be delayed or sometimes prevented in individuals with obesity who are able to lose weight. Weight loss can be achieved medically with behavioral therapies that combine diet and exercise treatment or with behavioral therapies combined with weight-loss medications or weight-loss surgery. In this article, we summarize the evidence of obesity management in treating T2DM and prediabetes. PMID:19793504

  12. Treating diabetes and prediabetes by focusing on obesity management.

    PubMed

    Khaodhiar, Lalita; Cummings, Sue; Apovian, Caroline M

    2009-10-01

    Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In obesity, the adipose cell releases nonesterified free fatty acids, hormones, adipocytokines, and other substances that are involved in insulin resistance. Under normal conditions, the pancreatic islet beta cells increase production of insulin sufficiently to maintain normal blood glucose concentrations despite insulin resistance. However, in genetically predisposed patients, the beta cells eventually become dysfunctional and T2DM develops. The development of T2DM can be delayed or sometimes prevented in individuals with obesity who are able to lose weight. Weight loss can be achieved medically with behavioral therapies that combine diet and exercise treatment or with behavioral therapies combined with weight-loss medications or weight-loss surgery. In this article, we summarize the evidence of obesity management in treating T2DM and prediabetes.

  13. Diabetes Remission after Nonsurgical Intensive Lifestyle Intervention in Obese Patients with Type 2 Diabetes

    PubMed Central

    Mottalib, Adham; Sakr, Mahmoud; Shehabeldin, Mohamed; Hamdy, Osama

    2015-01-01

    Partial or complete remission from type 2 diabetes was recently observed after bariatric surgeries. Limited data is available about the possibility of inducing diabetes remission through intensive weight reduction. We retrospectively evaluated diabetes remissions after one year of the Weight Achievement and Intensive Treatment (Why WAIT) program, a 12-week intensive program for diabetes weight management in real-world clinical practice. Among 120 obese patients with type 2 diabetes who completed the program, 88 patients returned for follow-up at one year. Nineteen patients (21.6%) had major improvement in their glycemic control, defined as achieving an A1C <6.5% after one year. Four patients (4.5%) achieved either partial or complete diabetes remission defined as A1C <6.5% and <5.7%, respectively, on no antihyperglycemic medications for one year; 2 achieved partial remission (2.3%) and 2 achieved complete remission (2.3%). At the time of intervention, patients who achieved diabetes remission had shorter diabetes duration (<5 years) and lower A1C (<8%) and were treated with fewer than 2 oral medications. They achieved a weight reduction of >7% after 12 weeks. These results indicate that a subset of obese patients with type 2 diabetes is appropriate for intensive lifestyle intervention with the aim of inducing diabetes remission. PMID:26114120

  14. Epigallocatechin gallate delays the onset of type 1 diabetes in spontaneous non-obese diabetic mice.

    PubMed

    Fu, Zhuo; Zhen, Wei; Yuskavage, Julia; Liu, Dongmin

    2011-04-01

    Type 1 diabetes (T1D) results from the autoimmune-mediated destruction of pancreatic β-cells, leading to deficiency of insulin production. Successful islet transplantation can normalise hyperglycaemia in T1D patients; however, the limited availability of the islets, loss of islet cell mass through apoptosis after islet isolation and potential autoimmune destruction of the transplanted islets prevent the widespread use of this procedure. Therefore, the search for novel and cost-effective agents that can prevent or treat T1D is extremely important to decrease the burden of morbidity from this disease. In the present study, we discovered that ( - )-epigallocatechin gallate (EGCG, 0·05 % in drinking-water), the primary polyphenolic component in green tea, effectively delayed the onset of T1D in non-obese diabetic (NOD) mice. At 32 weeks of age, eight (66·7 %) out of twelve mice in the control group developed diabetes, whereas only three (25 %) out of twelve mice in the EGCG-treated group became diabetic (P < 0·05). Consistently, mice supplemented with EGCG had significantly higher plasma insulin levels and survival rate but lower glycosylated Hb concentrations compared with the control animals. EGCG had no significant effects on food or water intake and body weight in mice, suggesting that the glucose-lowering effect was not due to an alteration in these parameters. While EGCG did not modulate insulitis, it elevated the circulating anti-inflammatory cytokine IL-10 level in NOD mice. These findings demonstrate that EGCG may be a novel, plant-derived compound capable of reducing the risk of T1D. PMID:21144096

  15. Imaging of Organ Metabolism in Obesity and Diabetes: Treatment Perspectives.

    PubMed

    Hannukainen, J C; Guzzardi, M A; Virtanen, K A; Sanguinetti, E; Nuutila, P; Iozzo, P

    2014-01-01

    Obesity and diabetes are growing threats for cardiovascular diseases (CVD) and heart failure. In order to identify early and effective treatment or prevention targets, it is fundamental to dissect the role of each organ and the sequence of events leading from health to obesity, diabetes and cardiovascular diseases. The advancements in imaging modalities to evaluate organ-specific metabolism in humans in vivo is substantially contributing to the stratification of risk, identification of organ-specific culprits and development of targeted treatment strategies. This review summarizes the contribution provided by imaging of the heart, skeletal muscle, adipose tissue, liver, pancreas, gut and brain to the understanding of the pathogenesis and cardio-metabolic complications of obesity and diabetes, and to the monitoring of treatment responses in humans. We conclude by suggesting emerging fields of investigation, including the role of cardiac fat in the pathogenesis of cardiovascular disease, the conversion of white into brown adipose tissue in the treatment of obesity, the control of weight and energy balance by the brain, the integration between omics and imaging technologies to help establish biomarkers, and the characterization of gut metabolism in relation with the gut microbiome, opening a very promising preventive/therapeutic perspective.

  16. Bariatric Surgery for People with Diabetes and Morbid Obesity

    PubMed Central

    2009-01-01

    Executive Summary In June 2008, the Medical Advisory Secretariat began work on the Diabetes Strategy Evidence Project, an evidence-based review of the literature surrounding strategies for successful management and treatment of diabetes. This project came about when the Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the Ministry’s newly released Diabetes Strategy. After an initial review of the strategy and consultation with experts, the secretariat identified five key areas in which evidence was needed. Evidence-based analyses have been prepared for each of these five areas: insulin pumps, behavioural interventions, bariatric surgery, home telemonitoring, and community based care. For each area, an economic analysis was completed where appropriate and is described in a separate report. To review these titles within the Diabetes Strategy Evidence series, please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/masabout.html, Diabetes Strategy Evidence Platform: Summary of Evidence-Based Analyses Continuous Subcutaneous Insulin Infusion Pumps for Type 1 and Type 2 Adult Diabetics: An Evidence-Based Analysis Behavioural Interventions for Type 2 Diabetes: An Evidence-Based Analysis Bariatric Surgery for People with Diabetes and Morbid Obesity: An Evidence-Based Summary Community-Based Care for the Management of Type 2 Diabetes: An Evidence-Based Analysis Home Telemonitoring for Type 2 Diabetes: An Evidence-Based Analysis Application of the Ontario Diabetes Economic Model (ODEM) to Determine the Cost-effectiveness and Budget Impact of Selected Type 2 Diabetes Interventions in Ontario Objective The purpose of this evidence-based analysis was to examine the effectiveness and cost-effectiveness of bariatric surgery for the management of diabetes in morbidly obese people. This report summarized evidence specific

  17. A proteomic approach to obesity and type 2 diabetes

    PubMed Central

    López-Villar, Elena; Martos-Moreno, Gabriel Á; Chowen, Julie A; Okada, Shigeru; Kopchick, John J; Argente, Jesús

    2015-01-01

    The incidence of obesity and type diabetes 2 has increased dramatically resulting in an increased interest in its biomedical relevance. However, the mechanisms that trigger the development of diabetes type 2 in obese patients remain largely unknown. Scientific, clinical and pharmaceutical communities are dedicating vast resources to unravel this issue by applying different omics tools. During the last decade, the advances in proteomic approaches and the Human Proteome Organization have opened and are opening a new door that may be helpful in the identification of patients at risk and to improve current therapies. Here, we briefly review some of the advances in our understanding of type 2 diabetes that have occurred through the application of proteomics. We also review, in detail, the current improvements in proteomic methodologies and new strategies that could be employed to further advance our understanding of this pathology. By applying these new proteomic advances, novel therapeutic and/or diagnostic protein targets will be discovered in the obesity/Type 2 diabetes area. PMID:25960181

  18. A proteomic approach to obesity and type 2 diabetes.

    PubMed

    López-Villar, Elena; Martos-Moreno, Gabriel Á; Chowen, Julie A; Okada, Shigeru; Kopchick, John J; Argente, Jesús

    2015-07-01

    The incidence of obesity and type diabetes 2 has increased dramatically resulting in an increased interest in its biomedical relevance. However, the mechanisms that trigger the development of diabetes type 2 in obese patients remain largely unknown. Scientific, clinical and pharmaceutical communities are dedicating vast resources to unravel this issue by applying different omics tools. During the last decade, the advances in proteomic approaches and the Human Proteome Organization have opened and are opening a new door that may be helpful in the identification of patients at risk and to improve current therapies. Here, we briefly review some of the advances in our understanding of type 2 diabetes that have occurred through the application of proteomics. We also review, in detail, the current improvements in proteomic methodologies and new strategies that could be employed to further advance our understanding of this pathology. By applying these new proteomic advances, novel therapeutic and/or diagnostic protein targets will be discovered in the obesity/Type 2 diabetes area.

  19. Prospective study of the link between overweight/obesity and diabetes incidence among Mexican older adults: 2001-2012

    PubMed Central

    Pinto, Guido; Beltrán-Sánchez, Hiram

    2015-01-01

    Objective To prospectively assess the relationship between overweight/obesity and incidence of type 2 diabetes mellitus (T2DM) among Mexicans aged 50+, assessing effects of age, genetic predisposition,education,physical activity,and place of residence. Materials and methods The Mexican Health and Aging Study (MHAS) was used to prospectively follow respondents free of diabetes in 2001 who became diabetic by 2012. Multivariate random effects logistic regression was used to assess covariates effects on the incidence of T2DM. Results Obese or overweight individuals at baseline (2001) were about 3 and 2 times,respectively,significantly more likely to become diabetic by 2012.Genetic predisposition increases the risk of diabetes by about three times compared to those with no family history of diabetes. Conclusion Overweight/obesity and genetic predisposition are the primary drivers of diabetes incidence among Mexican older adults. Reducing body weight and having access to health care may ameliorate the disease burden of T2DM. PMID:26172229

  20. Timing of bariatric surgery in people with obesity and diabetes.

    PubMed

    Busetto, Luca

    2015-05-01

    The use of bariatric surgery in the clinical management of type 2 diabetes in severely obese subjects has been included in the clinical practice recommendations released by the most influential diabetologic associations. However, the timing during the diabetic course in which this use may have the better benefit/risk ratio remains debated. Is it better to use surgery very early in the course of the disease in order to anticipate clinical deterioration, or we should favour a delayed approach in which we reserve the more risky surgery only to patients not adequately controlled with the maximal pharmacologic strategy? In this paper, past and recent evidences about the role of bariatric surgery in the different stages of the clinical course of type 2 diabetes have been revised, starting from pre-diabetes and ending to long-standing diabetic state with established or end-stage macro- and micro-vascular complications. Available evidences strongly advocate in favor of the application of bariatric surgery in the early phase of this course, possibly in the pre-diabetic or in very early diabetic stages. To reserve surgery to more advanced and complicated stages of the disease seems to confer less benefits for the clinical course of diabetes and exposes these more frail patients to the possible side effects of a rapid weight loss.

  1. Differences in the management of hypertension, diabetes mellitus and dyslipidemia between obesity classes.

    PubMed

    Martínez-St John, D R J; Palazón-Bru, A; Gil-Guillén, V F; Sepehri, A; Navarro-Cremades, F; Orozco-Beltrán, D; Carratalá-Munuera, C; Cortés, E; Rizo-Baeza, M M

    2016-01-01

    We did not find any paper that assessed clinical inertia in obese patients. Therefore, no paper has compared the clinical inertia rates between morbidly and nonmorbidly obese patients. A cross-sectional observational study was carried out. We analysed 8687 obese patients ⩾40 years of age who attended their health-care center for a checkup as part of a preventive program. The outcome was morbid obesity. Secondary variables were as follows: failure in the management of high blood pressure (HBP), high blood cholesterol (HBC) and high fasting blood glucose (HFBG); gender; personal history of hypertension, dyslipidemia, diabetes, smoking and cardiovascular disease; and age (years). We analysed the association between failures and morbid obesity by calculating the adjusted odds ratio (OR). Of 8687 obese patients, 421 had morbid obesity (4.8%, 95% confidence interval (CI): 4.4-5.3%). The prevalence rates for failures were as follows: HBP, 34.7%; HBC, 35.2%; and HFBG, 12.4%. Associated factors with morbid obesity related with failures were as follows: failure in the management of HBP (OR=1.42, 95% CI: 1.15-1.74, P=0.001); failure in the management of HBC (OR=0.73, 95% CI: 0.58-0.91, P=0.004); and failure in the management of HFBG (OR=2.24, 95% CI: 1.66-3.03, P<0.001). Morbidly obese patients faced worse management for HBP and HFBG, and better management for HBC. It would be interesting to integrate alarm systems to avoid this problem.

  2. Diabetes prevention: Reproductive age women affected by insulin resistance.

    PubMed

    Rezai, Shadi; LoBue, Stephen; Henderson, Cassandra E

    2016-07-01

    In the United States, 29.1 million people are affected by diabetes, of which 95% have type 2 diabetes. There has been a fivefold increase in type 2 diabetes in the latter half of the 20th century, an increase strongly linked to the obesity epidemic in the United States. In addition, insulin resistance affects 86 million Americans, or more than one-third of the adult population, as manifested by impaired fasting glucose tolerance with random glucose values ranging from ⩾100 to <126 mg/dL. In all, 90% of those affected by impaired fasting glucose tolerance or pre-diabetes are unaware of their metabolic derangement. Although impaired fasting glucose tolerance increases one's risk of developing type 2 diabetes, once identified, application of lifestyle changes by affected individuals may avoid or delay the onset of type 2 diabetes. For reproductive age women who are found to have impaired fasting glucose tolerance, lifestyle changes may be an effective tool to diminish the reproductive health consequences of insulin resistance related diseases. PMID:27638898

  3. Obesity, Diabetes, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union

    PubMed Central

    Legler, Juliette; Fletcher, Tony; Govarts, Eva; Porta, Miquel; Blumberg, Bruce; Heindel, Jerrold J.

    2015-01-01

    Context: Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. Objective: The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. Design: An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimation as of 2010 utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention: Cost estimation was performed from the societal perspective. Results: The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 (sensitivity analysis: 1555–5463) in 2010 with associated costs of €24.6 million (sensitivity analysis: €24.6–86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200–56 400) with associated costs of €835 million (sensitivity analysis: €835 million–16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion

  4. Maternal gestational diabetes mellitus and overweight and obesity in offspring: a study in Chinese children.

    PubMed

    Zhao, Y L; Ma, R M; Lao, T T; Chen, Z; Du, M Y; Liang, K; Huang, Y K; Zhang, L; Yang, M H; Sun, Y H; Li, H; Ding, Z B

    2015-12-01

    The purpose of this study was to investigate the effects of maternal gestational diabetes mellitus (GDM) and breast feeding on childhood overweight and obesity in a mainland Chinese population. The incidence of and factors associated with overweight and obesity were compared between children of mothers with (n=1068) and without (n=1756) GDM. The independent roles of the associated factors were examined by multiple logistic regression analysis. The incidence of overweight was higher (16.6 v. 12.6%, P=0.002) in the GDM group, but that of obesity was not different (10.7 v. 12.0%, P=0.315). At age 1-2 and 2-5 years, no difference in overweight (11.0 v. 12.0%, P=0.917, and 15.7 v. 14.6%, P=0.693, respectively) was found, while obesity (8.0 v. 13.6%, P=0.019, and 8.4 v. 13.4%, P=0.014, respectively) was less frequent in the GDM offspring. At age 5-10 years, increased overweight (22.2 v. 12.1%, P<0.001) and obesity (15.9 v. 9.0%, P=0.001) were found in the GDM group, which was associated with maternal obesity, being born large-for-gestational age, male gender and formula feeding. After adjusting for confounding factors, GDM remained an independent determinant of offspring overweight and obesity (aOR 2.28, 95% CI 1.61-3.22), suggesting that the effects of GDM were independent of breast feeding, as well as of maternal obesity and birth size.

  5. Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects.

    PubMed

    Chattopadhyay, Mrittika; Khemka, Vineet Kumar; Chatterjee, Gargi; Ganguly, Anirban; Mukhopadhyay, Satinath; Chakrabarti, Sasanka

    2015-01-01

    Oxidative stress in the insulin target tissues has been implicated in the pathophysiology of type 2 diabetes. The study has examined the oxidative stress parameters in the mitochondria of subcutaneous white adipose tissue from obese and non-obese subjects with or without type 2 diabetes. An accumulation of protein carbonyls, fluorescent lipid peroxidation products, and malondialdehyde occurs in the adipose tissue mitochondria of obese type 2 diabetic, non-diabetic obese, and non-obese diabetic subjects with the maximum increase noticed in the obese type 2 diabetes patients and the minimum in non-obese type 2 diabetics. The mitochondria from obese type 2 diabetics, non-diabetic obese, and non-obese type 2 diabetics also produce significantly more reactive oxygen species (ROS) in vitro compared to those of controls, and apparently the mitochondrial ROS production rate in each group is proportional to the respective load of oxidative damage markers. Likewise, the mitochondrial antioxidant enzymes like superoxide dismutase and glutathione peroxidase show decreased activities most markedly in obese type 2 diabetes subjects and to a lesser degree in non-obese type 2 diabetes or non-diabetic obese subjects in comparison to control. The results imply that mitochondrial dysfunction with enhanced ROS production may contribute to the metabolic abnormality of adipose tissue in obesity and diabetes.

  6. [Obesity, hypertension, and diabetes mellitus among school children in Ouagadougou (Burkina Faso)].

    PubMed

    Ye, D; Drabo, Y J; Ouedraogo, D; Samandoulougou, A; Sawadogo, A

    2001-01-01

    This paper deals with the findings of a survey conducted at the school environnement in Ouagadougou. Three factors of cardiovascular risks were identified: obesity, high blood pressure, and diabete millitus. The survey was based on a sample of 1470 students from primary and secondary schools consisted in taking their blood pressure, measuring they weight and height and glycaemia using dextrostix. Of the 1470 students targeted, 668 were girls and 782 were boys. Their age ranges between 4 and 25 years with average age of 13.8 years. 55 % of the students had an average socio-economic backgrounds. 58 students or 3.94% had high blood pressure including 50 cases of maximum high blood pressure and 8 cases of confirmed high blood pressure (HBP). A diastolic HBP predominance among 48 cases or 3.26% was also recorded. While 1 case showed systolic HBP, 6 were systolo-diastolic. The quetelet index used to determine obesity revealed 28 cases of excess in weight or 1.90% of the cases and 4 cases of obesity, or 0.28%. The predominance of excess in weight was statistically significant among girls. Only 1 case of obesity was associated with high blood pressure. No case of diabetes was identified. The factors of cardiovascular risk seem to be statistically important in school environnement in Ouagadougou. However, an muticentered study is recommended, as it will lead to an exhaustive knowledge of the prevalence of these factors of cardiovascular risk.

  7. Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder

    PubMed Central

    Marquie-Beck, J.A.; FitzSimons, C.A.; Letendre, S.L.; Ellis, R.J.; Heaton, R.K.; Wolfson, T.; Rosario, D.; Alexander, T.J.; Marra, C.; Ances, B.M.; Grant, I.

    2012-01-01

    Objective: To evaluate relationships between HIV-associated neurocognitive disorder and metabolic variables in a subgroup of HIV+ participants examined in a prospective, observational, multicenter cohort study. Methods: In a cross-sectional substudy of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort, 130 HIV+ participants provided fasting blood samples. Neurocognitive impairment (NCI) was defined by performance on neuropsychological tests adjusting for age, education, gender, and race/ethnicity. Global ratings and global deficit scores were determined. Demographics, biomarkers of HIV disease, metabolic variables, combination antiretroviral therapy (CART) history, other drug exposures, and self-reported diabetes were examined in multivariate models predicting NCI. Separate models were used for body mass index (BMI) alone (n = 90) and BMI and waist circumference (WC) together (n = 55). Results: NCI (global impairment rating ≥5) was diagnosed in 40%. In univariate analyses, age, longer duration of HIV infection, obesity, and WC, but not BMI, were associated with NCI. Self-reported diabetes was associated with NCI in the substudy and in those >55 in the entire CHARTER cohort. Multivariate logistic regression analyses demonstrated that central obesity (as measured by WC) increased the risk of NCI and that greater body mass may be protective if the deleterious effect of central obesity is accounted for. Conclusions: As in HIV-uninfected persons, central obesity, but not more generalized increases in body mass (BMI), was associated with a higher prevalence of NCI in HIV+ persons. Diabetes appeared to be associated with NCI only in older patients. Avoidance of antiretroviral drugs that induce central obesity might protect from or help to reverse neurocognitive impairment in HIV-infected persons. PMID:22330412

  8. Pharmacogenomics of cardiovascular complications in diabetes and obesity.

    PubMed

    Chapalamadugu, Kalyan; Panguluri, Siva K; Miranda, Aimon; Sneed, Kevin B; Tipparaju, Srinivas M

    2014-01-01

    Heart disease is a major cause of death in US and worldwide. The complex interplay of the mechanisms between diabetes, obesity and inflammation raises concerns for therapeutic understanding and developing treatment options for patients. Recent advances utilizing pharmacogenomics has helped researchers to probe in to disease pathophysiology and physicians to detect and, diagnose the disease in patients. The understanding developed in the area primarily addresses the issue focusing on the nature and asks the question 'Why' some individuals respond to the standard medication regimen and others do not. The central idea that genomics play a vital part in how the healthcare providers: physician, pharmacist, and nurse provide treatment utilizing the best practices available for maximum benefits. Pharmacogenomics is the scientific basis which offers the fundamental understanding for diseases, based on which therapeutic approaches can be designed and delivered. The discovery that not all humans respond to the drug in the same way is a 'paradigm shift' in how current therapies are offered. The area of pharmacogenomics at its core is linked to the genetic basis for the disease and the response to treatment. Given that diabetes and obesity are major metabolic ailments globally wherein patients also often suffer from cardiac disorders, a comprehensive genetic and pharmacogenomic understanding of these conditions enable the development of effective therapeutic strategies. In this review, we discuss various pharmacogenomic approaches with special emphasis on heart disease as it relates to diabetes and obesity. Recent information in regard to relevant patents in this topic are also discussed. PMID:25185978

  9. Severe pulmonary metastasis in obese and diabetic mice.

    PubMed

    Mori, Akinori; Sakurai, Hiroaki; Choo, Min-Kyung; Obi, Ryosuke; Koizumi, Keiichi; Yoshida, Chiho; Shimada, Yutaka; Saiki, Ikuo

    2006-12-15

    Although obesity is known as a risk factor for several human cancers, the association of obesity with cancer recurrence and metastasis remains to be characterized. Here, B16-BL6 melanoma and Lewis lung carcinoma cells were intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number of experimental lung colonies was markedly promoted in these mice when compared with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable when cells were inoculated orthotopically. The use of B16-BL6 cells stably transfected with the luciferase gene revealed that the increased metastasis reflected a difference mainly within 6 hr after the intravenous inoculation of tumor cells. Administration of recombinant leptin in ob/ob mice abolished the increase in metastasis early on as well as the decrease in the splenic NK cell number. In addition, depletion of NK cells by an anti-asialo-GM1 antibody abrogated the enhanced metastasis in db/db mice. These results demonstrate that metastasis is markedly promoted in diabetic and obese mice mainly because of decreased NK cell function during the early phase of metastasis. PMID:16998795

  10. Are We in the Same Risk of Diabetes Mellitus? Gender- and Age-Specific Epidemiology of Diabetes in 2001 to 2014 in the Korean Population

    PubMed Central

    Koo, Bo Kyung

    2016-01-01

    In the early 2000s, the prevalence of diabetes in adults aged ≥30 years in Korea was about 9% to 10%, and it remained stable. However, a nationwide survey showed that this prevalence increased over the past few years. After age-standardization using the Korean population of the year 2010, the prevalence of diabetes in adults aged ≥30 years was 10.0% to 10.8% between 2001 and 2012, which increased to 12.5% in 2013 and 11.6% in 2014. During that period, there have been changes in the gender- and age-specific prevalence of diabetes in Korean adults. The prevalence of diabetes in the elderly population increased significantly, while this prevalence in young adults, especially in young women, did not change significantly. The contribution of each diabetic risk factor, such as obesity, β-cell dysfunction, sarcopenia, and socioeconomic status, in developing diabetes has also changed during that period in each gender and age group. For young women, obesity was the most important risk factor; by contrast, for elderly diabetic patients, sarcopenia was more important than obesity as a risk factor. Considering the economic burden of diabetes and its associated comorbidities, a public health policy targeting the major risk factors in each population might be more effective in preventing diabetes. PMID:27273907

  11. Obesity, Islet Cell Autoimmunity, and Cardiovascular Risk Factors in Youth at Onset of Type 1 Autoimmune Diabetes

    PubMed Central

    Cedillo, Maribel; Arena, Vincent C.; Zhou, Lei; Trucco, Massimo; Ize-Ludlow, Diego; Pietropaolo, Massimo; Becker, Dorothy J.

    2015-01-01

    Context: The current increase in childhood type 1 diabetes (T1D) and obesity has led to two conflicting hypotheses and conflicting reports regarding the effects of overweight on initiation and spreading of islet cell autoimmunity vs earlier clinical manifestation of preexisting autoimmune β-cell damage driven by excess weight. Objective: The objective of the study was to address the question of whether the degree of β-cell autoimmunity and age are related to overweight at diabetes onset in a large cohort of T1D youth. Design: This was a prospective cross-sectional study of youth with autoimmune T1D consecutively recruited at diabetes onset. Setting: The study was conducted at a regional academic pediatric diabetes center. Patients: Two hundred sixty-three consecutive children younger than 19 years at onset of T1D participated in the study. Main Outcome Measures: Relationships between body mass index and central obesity (waist circumference and waist to height ratio) and antigen spreading (islet cell autoantibody number), age, and cardiovascular (CVD) risk factors examined at onset and/or 3 months after the diagnosis were measured. Results: There were no significant associations between number of autoantibodies with measures of adiposity. Age relationships revealed that a greater proportion of those with central obesity (21%) were in the youngest age group (0–4 y) compared with those without central obesity (6%) (P = .001). Patients with central obesity had increased CVD risk factors and higher onset C-peptide levels (P < .05). Conclusions: No evidence was found to support the concept that obesity accelerates progression of autoantibody spreading once autoimmunity, marked by standard islet cell autoantibody assays, is present. Central obesity was present in almost one-third of the subjects and was associated with early CVD risk markers already at onset. PMID:25250632

  12. The Impact of Obesity and Exercise on Cognitive Aging

    PubMed Central

    Chan, John S. Y.; Yan, Jin H.; Payne, V. Gregory

    2013-01-01

    Obesity is a major concern in the aging population and degrades health, motor functions and cognition in older adults. The effects of obesity are pervasive and challenging to health-care systems, making this a widespread and critically important public health dilemma. In this review, we examine the relationship between obesity, cognitive aging, and related dysfunctions. Potential neural mechanisms underlying such relationship are described. We propose that cost-effective exercises can be employed to cope with obesity and cognitive declines in older adults. Finally, we discuss implications and future research directions. PMID:24391586

  13. Morbid obesity in pediatric diabetes mellitus: surgical options and outcomes.

    PubMed

    Brandt, Mary L; Harmon, Carroll M; Helmrath, Michael A; Inge, Thomas H; McKay, Siripoom V; Michalsky, Marc P

    2010-11-01

    The current obesity epidemic has led to a dramatic increase in insulin resistance and type 2 diabetes mellitus among adolescents, along with other obesity-related comorbidities, such as hypertension, hyperlipidemia, obstructive sleep apnea, psychosocial impairment and nonalcoholic fatty liver disease. Medical treatment of severe obesity is effective in only a small percentage of adolescent patients. In light of the potentially life-threatening complications of obesity, bariatric surgery can be considered a treatment option for adolescent patients with morbid obesity. Indications for surgery rely on both BMI and comorbidity criteria, as well as the ability of the adolescents and their family to understand and comply with perioperative protocols. The long-term effects of bariatric surgery in adolescents are not known; therefore, participation in prospective outcome studies is important. The risk associated with bariatric surgery in adolescents seems to be similar to that observed in adult patients in the short term. Data suggest that bypass procedures successfully reverse or improve abnormal glucose metabolism in the majority of patients and may be more effective in adolescents than adults. This improvement in glucose metabolism occurs before marked weight loss in patients undergoing bypass procedures, suggesting a direct effect on the hormonal control of glucose metabolism.

  14. The Prevalence of Overweight and Obesity Among Aging Female Inmates.

    PubMed

    Leigey, Margaret E; Johnston, Mary E

    2015-07-01

    The purpose of this study was to examine the prevalence of overweight and obesity in a sample of older female inmates (N = 458). Results indicate that 34% of older female inmates were overweight and 36% were obese; similar percentages were noted for the general population. Race and age were found to be significantly associated with the body mass index categories of healthy weight and obese. White inmates were significantly more likely to be of a healthy weight and significantly less likely to be obese than Black inmates. Age was positively associated with healthy weight and negatively associated with obesity. These two variables remained significant even after they were introduced into logistic regression models predicting healthy weight and obesity. Findings indicate the need for programming to improve the health of this population.

  15. Improvement of Type 2 Diabetes Mellitus in Obese and Non-Obese Patients after the Duodenal Switch Operation

    PubMed Central

    Frenken, M.; Cho, E. Y.; Karcz, W. K.; Grueneberger, J.; Kuesters, S.

    2011-01-01

    Introduction. Type 2 diabetes mellitus (T2DM) is one of the most important obesity-related comorbidities. This study was undertaken to characterise the effect of the biliopancreatic diversion with duodenal switch (BPD-DS) in morbidly obese and nonmorbidly obese diabetic patients. Methods. Outcome of 74 obese diabetic patients after BPD-DS and 16 non-obese diabetic patients after BPD or gastric bypass surgery was evaluated. Insulin usage, HbA1c-levels, and index of HOMA-IR (homeostasis model assessment of insulin resistence) were measured. Results. A substantial fraction of patients is free of insulin and shows an improved insulin sensitivity early after the operation, another fraction gets free of insulin in a 12-month period after the operation and a small fraction of long-term insulin users will not get free of insulin but nevertheless shows an improved metabolic status (less insulin needed, normal HbA1c-levels). Conclusion. BPD-DS leads to an improvement of T2DM in obese and non-obese patients. Nevertheless, more data is needed to clarify indications and mechanisms of action and to adjust our operation techniques to the needs of non-obese diabetic patients. PMID:21461399

  16. Obesity and Coronary Artery Calcium in Diabetes: The Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study

    PubMed Central

    Rodrigues, Ticiana C.; Veyna, Adrienne M.; Haarhues, Michelle D.; Kinney, Gregory L.; Rewers, Marian

    2011-01-01

    Abstract Background The aim was to examine whether excess weight is associated with coronary artery calcium (CAC), independent of metabolic parameters in adults with type 1 diabetes (T1D). Methods Subjects between 19 and 56 years of age with T1D (n=621) from the Coronary Artery Calcification in Type 1 Diabetes study were classified as abnormal on four metabolic parameters: blood pressure ≥130/85 mm Hg or on antihypertensive treatment; high-density lipoprotein-cholesterol of <40 mg/dL for men or <50 mg/dL for women; triglycerides of ≥150 mg/dL; or C-reactive protein of ≥3 μg/mL. Study participants with two or more abnormal parameters were classified as metabolically abnormal. Weight categories by body mass index were normal (<25 kg/m2), overweight (25 to <30 kg/m2), and obese (≥30 kg/m2). CAC was measured at two visits 6.0±0.5 years apart. Progression of CAC was defined as an increase in square root transformed CAC volume of ≥2.5 mm3 or development of clinical coronary artery disease. Results Among subjects with T1D, 48% of normal, 61% of overweight, and 73% of obese participants were classified as metabolically abnormal (P<0.0001). Overweight and obesity were independently associated with presence of CAC, independent of presence of metabolically abnormal. Obesity but not overweight was associated with CAC progression, independent of the other cardiovascular risk factors. Conclusions Although obesity is known to increase cardiovascular disease risk through inducing metabolic abnormalities such as dyslipidemia, hypertension, and inflammation, it is also a strong predictor of subclinical atherosclerosis progression in adults with T1D independent of these factors. PMID:21770813

  17. Visceral Fat Mass Has Stronger Associations with Diabetes and Prediabetes than Other Anthropometric Obesity Indicators among Korean Adults

    PubMed Central

    Jung, Suk Hwa; Ha, Kyoung Hwa

    2016-01-01

    Purpose This study determined which obesity measurement correlates the best with diabetes and prediabetes. Materials and Methods This cross-sectional study enrolled 1603 subjects (611 men, 992 women; age 30–64 years) at the Cardiovascular and Metabolic Diseases Etiology Research Center. Body mass index, waist circumference, waist-height ratio, waist-hip ratio, waist-thigh ratio, and visceral fat were used as measures of obesity. Visceral fat was acquired using dual-energy X-ray absorptiometry (DXA). The prevalences of diabetes and prediabetes were defined using the criteria in the American Diabetes Association 2015 guidelines. Results After adjusting for age and other potential confounding factors, participants with a visceral fat mass in the upper 10th percentile had a higher odds ratio (OR) for diabetes and prediabetes than the upper 10th percentile of other adiposity indices [men, OR=15.9, 95% confidence interval (CI)=6.4–39.2; women, OR=6.9, 95% CI=3.5–13.7]. Visceral fat mass also had the highest area under the curve with diabetes and prediabetes in both men (0.69, 95% CI=0.64–0.73) and women (0.70, 95% CI=0.67–0.74) compared to other anthropometric measurements of obesity. Conclusion Visceral fat mass measured using DXA is an indicator of diabetes or prediabetes, due to its ability to differentiate between abdominal visceral and subcutaneous fat. PMID:26996568

  18. High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance

    PubMed Central

    Lu, Chia-Wen; Chang, Hao-Hsiang; Yang, Kuen-Cheh; Kuo, Chia-Sheng; Lee, Long-Teng; Huang, Kuo-Chin

    2016-01-01

    Objective Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity. Research design and methods This was a hospital-based case–control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses. Results After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32). Conclusions We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation. PMID:27547419

  19. Brd2 gene disruption causes ‘metabolically healthy’ obesity: Epigenetic and chromatin-based mechanisms that uncouple obesity from Type 2 diabetes

    PubMed Central

    Wang, Fangnian; Deeney, Jude T.; Denis, Gerald V.

    2014-01-01

    Disturbed body energy balance can lead to obesity and obesity-driven diseases such as Type 2 diabetes, which have reached an epidemic level. Evidence indicates that obesity induced inflammation is a major cause of insulin resistance and Type 2 diabetes. Environmental factors, such as nutrients, affect body energy balance through epigenetic or chromatin-based mechanisms. As a bromodomain and external domain family transcription regulator, Brd2 regulates expression of many genes through interpretation of chromatin codes, and participates in the regulation of body energy balance and immune function. In the severely obese state, Brd2 knockdown in mice prevented obesity-induced inflammatory responses, protected animals from Type 2 diabetes, and thus uncoupled obesity from diabetes. Brd2 provides an important model for investigation of the function of transcription regulators and the development of obesity and diabetes; it also provides a possible target to treat obesity and diabetes through modulation of the function of a chromatin code reader. PMID:23374712

  20. Adipose tissue angiogenesis: impact on obesity and type-2 diabetes.

    PubMed

    Corvera, Silvia; Gealekman, Olga

    2014-03-01

    The growth and function of tissues are critically dependent on their vascularization. Adipose tissue is capable of expanding many-fold during adulthood, therefore requiring the formation of new vasculature to supply growing and proliferating adipocytes. The expansion of the vasculature in adipose tissue occurs through angiogenesis, where new blood vessels develop from those pre-existing within the tissue. Inappropriate angiogenesis may underlie adipose tissue dysfunction in obesity, which in turn increases type-2 diabetes risk. In addition, genetic and developmental factors involved in vascular patterning may define the size and expandability of diverse adipose tissue depots, which are also associated with type-2 diabetes risk. Moreover, the adipose tissue vasculature appears to be the niche for pre-adipocyte precursors, and factors that affect angiogenesis may directly impact the generation of new adipocytes. Here we review recent advances on the basic mechanisms of angiogenesis, and on the role of angiogenesis in adipose tissue development and obesity. A substantial amount of data points to a deficit in adipose tissue angiogenesis as a contributing factor to insulin resistance and metabolic disease in obesity. These emerging findings support the concept of the adipose tissue vasculature as a source of new targets for metabolic disease therapies. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  1. Overweight and obesity in youth with type 1 diabetes.

    PubMed

    Minges, Karl E; Whittemore, Robin; Grey, Margaret

    2013-01-01

    Overweight and obesity in youth with type 1 diabetes (T1D) is now prevalent and accounts for significant health consequences, including cardiovascular complications and dual diagnosis of type 2 diabetes. Physical activity and lifestyle are modifiable and play an important role in the prevention and management of excessive weight, but it is unclear how these factors relate to overweight and obese youth with T1D. Thus, a systematic review was conducted to examine how physical activity, sedentary behavior, sleep, and diet are related to overweight/obesity in youth with T1D. Seven observational and intervention studies published between 1990 and 2013 were included in the review. Prevalence of overweight ranged from 12.5% to 33.3%. Overweight in youth with T1D was associated with infrequent napping, increased screen time, and skipping breakfast and dinner but was not related to time engaged in physical activity. Weight-related interventions indicated modest weight loss along with improved glycemic control. In light of this review, there is a need for high quality research that examines all levels of activity in youth with T1D to identify lifestyle modification targets for weight prevention and management.

  2. Interaction of smoking and obesity on type 2 diabetes risk in a Chinese cohort.

    PubMed

    Luo, Wenshu; Guo, Zhirong; Wu, Ming; Hao, Chao; Zhou, Zhengyuan; Yao, Xingjuan

    2015-02-01

    The aim of this study was to examine the independent and combined effects of current smoking and obesity on risk of type 2 diabetes (T2DM) in a Chinese cohort. We analyzed the data from a population-based prospective cohort of 3598 participants aged 35-74 years from Jiangsu, China. A Cox proportional hazards regression model was used to calculate the hazard ratio (HR) of T2DM and corresponding 95% confidence interval (CI), and to examine the interaction between current smoking and obesity on risk of T2DM. Compared with non-smokers, the hazard ratio of T2DM for current smokers was 4.16 (2.77-6.24). There was a significant interaction between current smoking and abdominal obesity on T2DM. RERI=2.84 (0.02-5.67), suggesting that there would be 2.84 relative excess risk due to the additive interaction; AP=0.48 (0.20-0.76), indicating that 48% of T2DM exposed to both risk factors was attributable to the additive interaction; and SI was 2.36 (1.15-4.87), suggesting that the risk of T2DM in obese smokers was 2.36 times as high as the sum of risks in the participants exposed to a single risk factor alone. We did not find a significant interaction between smoking and overall obesity on T2DM, but the incidence of T2DM in overall obese smokers was also highest. Both current smoking and abdominal obesity are strong risk factors of T2DM in the Chinese population. This study further demonstrates an additive interaction of current smoking and abdominal obesity on T2DM risk.

  3. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency.

    PubMed

    Boyanov, M A; Boneva, Z; Christov, V G

    2003-03-01

    The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis, obesity and sexual function in middle-aged men with type 2 diabetes and mild androgen deficiency. Forty-eight middle-aged men, with type 2 diabetes, (visceral) obesity and symptoms of androgen deficiency, were included in this open-label study. Twenty-four subjects received testosterone undecanoate (TU; 120 mg daily, for 3 months); 24 subjects received no treatment. Body composition was analyzed by bio-impedance. Parameters of metabolic control were determined. Symptoms of androgen deficiency and erectile dysfunction were scored by self-administered questionnaires. TU had a positive effect on (visceral) obesity: statistically significant reduction in body weight (2.66%), waist-hip ratio (-3.96%) and body fat (-5.65%); negligible changes were found in the control group. TU significantly improved metabolic control: decrease in blood glucose values and mean glycated hemoglobin (HbA1c) (from 10.4 to 8.6%). TU treatment significantly improved symptoms of androgen deficiency (including erectile dysfunction), with virtually no change in the control group. There were no adverse effects on blood pressure or hematological, biochemical and lipid parameters, and no adverse events. Oral TU treatment of type 2 diabetic men with androgen deficiency improves glucose homeostasis and body composition (decrease in visceral obesity), and improves symptoms of androgen deficiency (including erectile dysfunction). In these men, the benefit of testosterone supplementation therapy exceeds the correction of symptoms of androgen deficiency and also includes glucose homeostasis and metabolic control. PMID:12809074

  4. Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality

    PubMed Central

    LeRoith, Derek

    2015-01-01

    Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, and both are associated with an increased incidence and mortality from many cancers. The metabolic abnormalities associated with type 2 diabetes develop many years before the onset of diabetes and, therefore, may be contributing to cancer risk before individuals are aware that they are at risk. Multiple factors potentially contribute to the progression of cancer in obesity and type 2 diabetes, including hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, adipokines and cytokines, and the gut microbiome. These metabolic changes may contribute directly or indirectly to cancer progression. Intentional weight loss may protect against cancer development, and therapies for diabetes may prove to be effective adjuvant agents in reducing cancer progression. In this review we discuss the current epidemiology, basic science, and clinical data that link obesity, diabetes, and cancer and how treating obesity and type 2 diabetes could also reduce cancer risk and improve outcomes. PMID:26084689

  5. Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality.

    PubMed

    Gallagher, Emily Jane; LeRoith, Derek

    2015-07-01

    Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, and both are associated with an increased incidence and mortality from many cancers. The metabolic abnormalities associated with type 2 diabetes develop many years before the onset of diabetes and, therefore, may be contributing to cancer risk before individuals are aware that they are at risk. Multiple factors potentially contribute to the progression of cancer in obesity and type 2 diabetes, including hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, adipokines and cytokines, and the gut microbiome. These metabolic changes may contribute directly or indirectly to cancer progression. Intentional weight loss may protect against cancer development, and therapies for diabetes may prove to be effective adjuvant agents in reducing cancer progression. In this review we discuss the current epidemiology, basic science, and clinical data that link obesity, diabetes, and cancer and how treating obesity and type 2 diabetes could also reduce cancer risk and improve outcomes. PMID:26084689

  6. Hypertension increases with aging and obesity in chimpanzees (Pan troglodytes).

    PubMed

    Ely, John J; Zavaskis, Tony; Lammey, Michael L

    2013-01-01

    Cardiovascular disease is a primary cause of morbidity and mortality in captive chimpanzees. Four years of blood pressure (BP) data were analyzed from a captive former laboratory population of 201 healthy adult chimpanzees with assessment of age and obesity on elevated BP. Five different measures of obesity were compared: abdominal girth, basal metabolic rate, body-mass index (BMI), body weight, and surface area. Systolic BP varied by sex. Obesity did not influence male BP. For females, obesity was a significant determinant of BP. The best measure of female obesity was basal metabolic rate and the worst was BMI. Median systolic BP of healthy weight females (<54.5 kg) was significantly lower (128 mmHg) than overweight or obese females (140 mmHg), but both were lower than all males (147 mmHg). For diastolic BP, neither sex nor any of the five obesity measures was significant. But age was highly significant, with geriatric chimpanzees (>30 years) having higher median diastolic BP (74 mmHg) than young adults of 10-29 years of age (65 mmHg). By these criteria, 80% of this population is normotensive, 7% prehypertensive, and 13% hypertensive. In summary, systolic BP intervals required adjustment for obesity among females but not males. Diastolic BP required adjustment for advanced age (≥30 years). Use of these reference intervals can facilitate timely clinical care of captive chimpanzees. PMID:22968757

  7. Mouse Models of Diabetes, Obesity and Related Kidney Disease

    PubMed Central

    Glastras, Sarah J.; Chen, Hui; Teh, Rachel; McGrath, Rachel T.; Chen, Jason; Pollock, Carol A.; Wong, Muh Geot; Saad, Sonia

    2016-01-01

    Multiple rodent models have been used to study diabetic kidney disease (DKD). The purpose of the present study was to compare models of diabetes and obesity-induced metabolic syndrome and determine differences in renal outcomes. C57BL/6 male mice were fed either normal chow or high fat diet (HFD). At postnatal week 8, chow-fed mice were randomly assigned to low-dose streptozotocin (STZ, 55 mg/kg/day, five consecutive days) or vehicle control, whereas HFD-fed mice were given either one high-dose of STZ (100 mg/kg) or vehicle control. Intraperitoneal glucose tolerance tests were performed at Week 14, 20 and 30. Urinary albumin to creatinine ratio (ACR) and serum creatinine were measured, and renal structure was assessed using Periodic Acid Schiff (PAS) staining at Week 32. Results showed that chow-fed mice exposed to five doses of STZ resembled type 1 diabetes mellitus with a lean phenotype, hyperglycaemia, microalbuminuria and increased serum creatinine levels. Their kidneys demonstrated moderate tubular injury with evidence of tubular dilatation and glycogenated nuclear inclusion bodies. HFD-fed mice resembled metabolic syndrome as they were obese with dyslipidaemia, insulin resistance, and significantly impaired glucose tolerance. One dose STZ, in addition to HFD, did not worsen metabolic features (including fasting glucose, non esterified fatty acid, and triglyceride levels). There were significant increases in urinary ACR and serum creatinine levels, and renal structural changes were predominantly related to interstitial vacuolation and tubular dilatation in HFD-fed mice. PMID:27579698

  8. Mouse Models of Diabetes, Obesity and Related Kidney Disease.

    PubMed

    Glastras, Sarah J; Chen, Hui; Teh, Rachel; McGrath, Rachel T; Chen, Jason; Pollock, Carol A; Wong, Muh Geot; Saad, Sonia

    2016-01-01

    Multiple rodent models have been used to study diabetic kidney disease (DKD). The purpose of the present study was to compare models of diabetes and obesity-induced metabolic syndrome and determine differences in renal outcomes. C57BL/6 male mice were fed either normal chow or high fat diet (HFD). At postnatal week 8, chow-fed mice were randomly assigned to low-dose streptozotocin (STZ, 55 mg/kg/day, five consecutive days) or vehicle control, whereas HFD-fed mice were given either one high-dose of STZ (100 mg/kg) or vehicle control. Intraperitoneal glucose tolerance tests were performed at Week 14, 20 and 30. Urinary albumin to creatinine ratio (ACR) and serum creatinine were measured, and renal structure was assessed using Periodic Acid Schiff (PAS) staining at Week 32. Results showed that chow-fed mice exposed to five doses of STZ resembled type 1 diabetes mellitus with a lean phenotype, hyperglycaemia, microalbuminuria and increased serum creatinine levels. Their kidneys demonstrated moderate tubular injury with evidence of tubular dilatation and glycogenated nuclear inclusion bodies. HFD-fed mice resembled metabolic syndrome as they were obese with dyslipidaemia, insulin resistance, and significantly impaired glucose tolerance. One dose STZ, in addition to HFD, did not worsen metabolic features (including fasting glucose, non esterified fatty acid, and triglyceride levels). There were significant increases in urinary ACR and serum creatinine levels, and renal structural changes were predominantly related to interstitial vacuolation and tubular dilatation in HFD-fed mice. PMID:27579698

  9. Age-related deregulation of Aire and peripheral tissue antigen genes in the thymic stroma of non-obese diabetic (NOD) mice is associated with autoimmune type 1 diabetes mellitus (DM-1).

    PubMed

    Fornari, Thaís A; Donate, Paula B; Macedo, Claudia; Marques, Márcia M C; Magalhães, Danielle A; Passos, Geraldo A S

    2010-09-01

    Gene expression of peripheral tissue antigens (PTAs) in stromal medullary thymic epithelial cells (mTECs) is a key process to the negative selection of autoreactive thymocytes. This phenomenon was termed "promiscuous gene expression" (PGE), which is partially controlled by the Aire gene. Nevertheless, reasons for the correlation of Aire and PTAs with the emergence of autoimmune diseases are largely unknown, though it may be a result of a chronological effect. Although the effect of Aire mutations in pathogenic autoimmunity is well know, it could not be a unique cause for autoimmunity. Independently of mutations, temporal deregulation of Aire expression may imbalance Aire-dependent PTAs and/or wide PGE. This deregulation may be an early warning sign for autoimmune diseases as it guarantees autoantigen representation in the thymus. To assess this hypothesis, we studied the expression levels of Aire, Aire-dependent (Ins2) and Aire-independent (Gad67 and Col2a1) PTAs using real-time-PCR of the thymic stromal cells of NOD mice during the development of autoimmune type 1 diabetes mellitus (DM-1). Wide PGE was studied by microarrays in which the PTA genes were identified through parallel CD80(+) mTEC 3.10 cell line expression profiling. The results show that Aire gene was down-regulated in young pre-autoimmune (pre-diabetic) NOD mice. PGE and specific PTA genes were down-regulated in adult autoimmune diabetic animals. These findings represent evidence indicating that chronological deregulation of genes important to negative selection may be associated with the development of an autoimmune disease (DM-1) in mice.

  10. [Type 2 diabetes mellitus and obesity: should we treat the obesity or the diabetes?].

    PubMed

    García, Santiago Durán; Sanz, Santiago Durán; Sanz, Alejandro Durán

    2013-09-01

    In this article, we review the results that can be expected after significant weight loss in patients with type 2 diabetes mellitus. We provide consensus-based documentation supported by the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation on the importance of physical exercise, metabolic-bariatric surgery, and drug therapy. Lastly, we report the results of studies published in the last few years on glucagon-like peptide-1 analogs and the new family of oral drugs known as gliflozins, specifically studies published on dapagliflozin. PMID:24444519

  11. [Type 2 diabetes mellitus and obesity: should we treat the obesity or the diabetes?].

    PubMed

    García, Santiago Durán; Sanz, Santiago Durán; Sanz, Alejandro Durán

    2013-09-01

    In this article, we review the results that can be expected after significant weight loss in patients with type 2 diabetes mellitus. We provide consensus-based documentation supported by the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation on the importance of physical exercise, metabolic-bariatric surgery, and drug therapy. Lastly, we report the results of studies published in the last few years on glucagon-like peptide-1 analogs and the new family of oral drugs known as gliflozins, specifically studies published on dapagliflozin.

  12. Assessing the effect of weight and weight loss in obese persons with type 2 diabetes

    PubMed Central

    Curtis, Bradley; Hayes, Risa P; Fehnel, Sheri; Zografos, Laurie

    2008-01-01

    The objective of this study was to assess specific areas of life in which obesity affects individuals with type 2 diabetes mellitus (T2DM), and changes that obese persons with T2DM experience with weight loss of varying degrees. Thirty in-depth interviews were conducted in persons identified as: age ≥40 years, diagnosed with T2DM for ≥2 years, on oral antihyperglycemic medications >3 months, BMI 30–35 kg/m2, having attempted to lose weight in the last 2 years. Participants (60% female, mean age 53 years, 53% Caucasian, mean BMI 32.2 kg/m2) agreed that 5% weight loss, while not reflective of an ultimate goal, would be meaningful and important; benefits were expected to accrue in physical functioning, self-confidence, blood glucose levels, and motivation to keep losing weight. Participants reported the greatest effect of weight loss on energy, physical activity, mobility, pain, and clothes/appearance. Participants reported weight affecting mood, with feelings of depression and frustration most commonly described. This research indicates that weight loss is likely to affect health-related quality of life in obese individuals with T2DM. Given the purported weight loss benefits of many emerging diabetic medications, it will be important to include measures of weight-related quality of life in future clinical trials of these agents. PMID:21437152

  13. Orlistat in the prevention of diabetes in the obese patient

    PubMed Central

    Mancini, Marcio C; Halpern, Alfredo

    2008-01-01

    There has been an increase in the concern about preventing type 2 diabetes mellitus (T2DM), a disease with great and increasing prevalence. The prevalence of obesity, physical inactivity, Western processed diet, important risk factors for the development of T2DM, are also rising. Free fatty acids are increased in obesity and reduce insulin clearance and increase hepatic glucose production. Implementation of a healthy lifestyle has been show to slow the progression of impaired glucose tolerance to T2DM. Orlistat is an inhibitor of lipase activity, with proved efficacy in body weight reduction and long-term management of obesity and more favorable effects on carbohydrate metabolism and it was prospectively shown in XENDOS study that orlistat promoted long-term weight loss and prevented T2DM onset in obese individuals with normal and impaired glucose tolerance at baseline over four years. This benefit could be associated to the weight loss itself, to the limited absorption of lipids and reduction of plasma free fatty acids, to increased production of incretins or to modulation of secretion of cytokines by adipocytes, all effects secondary to orlistat treatment. A proposed strategy is to identify subjects at highest risk to receive a drug intervention, using lifestyle interventions alone at the community level. PMID:18561508

  14. Relationship of Soft Drink Consumption to Global Overweight, Obesity, and Diabetes: A Cross-National Analysis of 75 Countries

    PubMed Central

    McKee, Martin; Galea, Gauden; Stuckler, David

    2013-01-01

    Objectives. We estimated the relationship between soft drink consumption and obesity and diabetes worldwide. Methods. We used multivariate linear regression to estimate the association between soft drink consumption and overweight, obesity, and diabetes prevalence in 75 countries, controlling for other foods (cereals, meats, fruits and vegetables, oils, and total calories), income, urbanization, and aging. Data were obtained from the Euromonitor Global Market Information Database, the World Health Organization, and the International Diabetes Federation. Bottled water consumption, which increased with per-capita income in parallel to soft drink consumption, served as a natural control group. Results. Soft drink consumption increased globally from 9.5 gallons per person per year in 1997 to 11.4 gallons in 2010. A 1% rise in soft drink consumption was associated with an additional 4.8 overweight adults per 100 (adjusted B; 95% confidence interval [CI] = 3.1, 6.5), 2.3 obese adults per 100 (95% CI = 1.1, 3.5), and 0.3 adults with diabetes per 100 (95% CI = 0.1, 0.8). These findings remained robust in low- and middle-income countries. Conclusions. Soft drink consumption is significantly linked to overweight, obesity, and diabetes worldwide, including in low- and middle-income countries. PMID:23488503

  15. [Obesity, diabetes, cancer and cardiovascular risk: a trans-generational network].

    PubMed

    Guiducci, Letizia; Pasanisi, Emilio; Capati, Eugenia; Iozzo, Patricia

    2010-04-01

    The prevalence of obesity has reached epidemic proportions, predisposing to the development of type 2 diabetes, cardiovascular disease and cancer. Lifestyle and genetic heritability are causes of this phenomenon, together with the nutritional environment during intra-uterine life and birth weight. We examine the above mentioned relationships in the family tree of a patient with diabetes, central obesity and cardiovascular disease.

  16. A "Family-Based" Approach to the Treatment of Obese Type II Diabetic Patients.

    ERIC Educational Resources Information Center

    Wing, Rena R.; And Others

    1991-01-01

    Assigned 49 obese diabetic patients with obese spouses (diabetic or nondiabetic) to an alone or together (with spouses) treatment condition of behavioral weight control program. Found no significant differences in weight losses of patients at posttreatment or one-year followup, but did find that women did better when treated with their spouses,…

  17. Hypertension increases with Aging and Obesity in chimpanzees (Pan troglodytes)

    PubMed Central

    Ely, John J.; Zavaskis, Tony; Lammey, Michael L.

    2012-01-01

    Cardiovascular disease is a primary cause of morbidity and mortality in captive chimpanzees. Four years of blood pressure data was analyzed from a captive former laboratory population of 201 healthy adult chimpanzees with assessment of age and obesity on elevated blood pressure. Five different measures of obesity were compared: abdominal girth, basal metabolic rate, body-mass index (BMI), body weight and surface area. Systolic BP varied by sex. Obesity did not influence male BP. For females, obesity was a significant determinant of BP. The best measure of female obesity was basal metabolic rate and the worst was BMI. Median systolic BP of healthy weight females (<54.5 Kg) was significantly lower (128 mmHg) than overweight or obese females (140 mmHg), but both were lower than all males (147 mmHg). For diastolic BP, neither sex nor any of the 5 obesity measures was significant. But age was highly significant, with geriatric chimpanzees (> 30 years) having higher median diastolic blood pressure (74 mmHg) than young adults of 10–29 years old (65 mmHg). By these criteria, 80% of this population is normotensive, 7% pre-hypertensive and 13% hypertensive. In summary, systolic BP intervals required adjustment for obesity among females but not males. Diastolic BP required adjustment for advanced age (≥30 years). Use of these reference intervals can facilitate timely clinical care of captive chimpanzees. PMID:22968757

  18. Serum Circulating microRNA Profiling for Identification of Potential Type 2 Diabetes and Obesity Biomarkers

    PubMed Central

    Pescador, Nuria; Pérez-Barba, Milagros; Ibarra, José María; Corbatón, Arturo; Martínez-Larrad, María Teresa; Serrano-Ríos, Manuel

    2013-01-01

    Background and Aim MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes, including complex metabolic processes, such as energy and lipid metabolism, which have been studied in the context of diabetes and obesity. Some particular microRNAs have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. The aim of this profiling study was to characterize the expression of miRNA in serum samples of obese, nonobese diabetic and obese diabetic individuals to determine whether miRNA expression was deregulated in these serum samples and to identify whether any observed deregulation was specific to either obesity or diabetes or obesity with diabetes. Patients and Methods Thirteen patients with type 2 diabetes, 20 obese patients, 16 obese patients with type 2 diabetes and 20 healthy controls were selected for this study. MiRNA PCR panels were employed to screen serum levels of 739 miRNAs in pooled samples from these four groups. We compared the levels of circulating miRNAs between serum pools of each group. Individual validation of the twelve microRNAs selected as promising biomarkers was carried out using RT-qPCR. Results Three serum microRNAs, miR-138, miR-15b and miR-376a, were found to have potential as predictive biomarkers in obesity. Use of miR-138 or miR-376a provides a powerful predictive tool for distinguishing obese patients from normal healthy controls, diabetic patients, and obese diabetic patients. In addition, the combination of miR-503 and miR-138 can distinguish diabetic from obese diabetic patients. Conclusion This study is the first to show a panel of serum miRNAs for obesity, and compare them with miRNAs identified in serum for diabetes and obesity with diabetes. Our results support the use of some miRNAs extracted from serum samples as potential predictive tools for obesity and type 2 diabetes. PMID:24204780

  19. [Carbohydrate metabolism disorders among obese children and adolescents. Diabetes mellitus type 2].

    PubMed

    Sergeyev, E; Wagner, I; Neef, M; Adler, M; Körner, A; Kiess, W

    2013-04-01

    As obesity has become more prevalent, the incidence of type 2 diabetes mellitus in children and adolescents has also increased. Obesity during adolescence leads to an increased risk for disease and premature death during adulthood, independent of obesity during adulthood. Obesity is the major risk factor impacting insulin sensitivity. Subjects with insulin resistance are at risk for progression to diabetes. Type 2 diabetes mellitus in obese children and adolescents is frequently asymptomatic. It is essential to identify children at high risk who need aggressive lifestyle modification focused on weight reduction and increased physical activity. Early detection and therapy of obese children and adolescents with type 2 diabetes may reduce the risk of cardiometabolic consequences and other long-term complications in adulthood.

  20. Childhood obesity.

    PubMed

    Dean, Erin

    2016-08-31

    Essential facts Nearly one third of children aged 2-15 in England are overweight or obese. Younger generations are becoming obese at earlier ages and staying so for longer. Reducing obesity levels is a major public health challenge as the condition doubles the risk of dying prematurely. Obese adults are more likely to develop health conditions such as heart disease, type 2 diabetes and depression. Treating conditions related to obesity is a major financial burden on the NHS, costing more than £5 billion a year. PMID:27577286

  1. Obesity and non-insulin-dependent diabetes mellitus in Swiss-Webster mice associated with late-onset hepatocellular carcinoma.

    PubMed

    Lemke, Laura B; Rogers, Arlin B; Nambiar, Prashant R; Fox, James G

    2008-10-01

    Genetic mutations resulting in obesity and type 2 diabetes mellitus (T2D) are described for both inbred and outbred mice. However, no known mouse model completely recapitulates human T2D and its comorbidities. We identified a cohort of obese, male, outbred Swiss-Webster (SW) mice as polyuric, polydipsic, glucosuric, and hyperglycemic. Prevalence of glucosuria in the SW colony reached 60% (n=70) in males 8 weeks to 6 months of age. Despite severe obesity in some females, no females were diabetic. Pathologic findings in affected males included cachexia, dilated gastrointestinal tracts with poor muscular tone, pancreatic islet degeneration and atrophy with compensatory metaplasia and/or neogenesis, bacterial pyelonephritis, membranous glomerulopathy, and late-onset hepatic tumors with macrosteatosis, microsteatosis, and hydropic change in aged males. Serum insulin correlated with blood glucose in a nonlinear pattern, suggestive of islet exhaustion. Circulating leptin levels showed a weak inverse correlation with glucose. Diabetic males were bred with obese colony females to produce 20 male and 20 female offspring. Prevalence of diabetes in male offspring was 80% (16/20) with a median age of onset of 18 weeks. By contrast, no diabetic females were identified, despite being significantly more obese than males. Male predominance is likewise a feature of T2D in humans. To our knowledge, this is the first documentation of hepatocellular carcinoma and islet metaplasia and/or neogenesis in a spontaneous outbred mouse model of T2D. The SW availability and histopathologic features represent a promising new model for the study of T2D.

  2. Sphingolipids in Obesity, Type 2 Diabetes, and Metabolic Disease

    PubMed Central

    Russo, S.B.; Ross, J.S.; Cowart, L.A.

    2014-01-01

    Metabolic disease, including obesity and type 2 diabetes, constitutes a major emerging health crisis in Western nations. Although the symptoms and clinical pathology and physiology of these conditions are well understood, the molecular mechanisms underlying the disease process have largely remained obscure. Sphingolipids, a lipid class with both signaling and structural properties, have recently emerged as key players in most major tissues affected by diabetes and are required components in the molecular etiology of this disease. Indeed, sphingolipids have been shown to mediate loss of insulin sensitivity, to promote the characteristic diabetic pro-inflammatory state, and to induce cell death and dysfunction in important organs such as the pancreas and heart. Furthermore, plasma sphingolipid levels are emerging as potential biomarkers for the decompensation of insulin resistance to frank type 2 diabetes. Despite these discoveries, the roles of specific sphingolipid species and sphingolipid metabolic pathways remain obscure, and newly developed experimental approaches must be employed to elucidate the detailed molecular mechanisms necessary for rational drug development and other clinical applications. PMID:23563667

  3. Obesity indices and adipokines in non-diabetic obese patients with early stages of chronic kidney disease

    PubMed Central

    Stępień, Mariusz; Stępień, Anna; Wlazeł, Rafał Nikodem; Paradowski, Marek; Banach, Maciej; Rysz, Magdalena; Rysz, Jacek

    2013-01-01

    Background The aim of this study was to estimate obesity parameters: waist circumference (WC), waist-to-hip ratio (WHR), weight-to-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI), and serum adipokines (leptin, adiponectin, resistin) and their associations with estimated glomerular filtration rate (eGFR), serum creatinine, and microalbuminuria (MA) in patients with early stages of CKD and in non-CKD obese patients. Material/Methods 67 non-diabetic obese (BMI ≥30 mg/kg2) out-clinic patients (25 males, 42 females), aged from 36.5 to 64 years were divided into 2 groups: Group A (n=15) – patients with early stages of CKD (eGFR between 30 and 60 ml/min/1.73 m2 or with MA >20 mg/l in morning urine sample independently from GFR) and Group B – patients without chronic CKD (n=52). Results In Group A compared to Group B, BAI and leptin were higher (42.2±7.1 vs. 37.5±7.0; p<0.05 and 51.8±26.7 ng/mL vs. 35.3±24.9 ng/mL; p<0.05; respectively) and negative correlations occurred between eGFR and BAI (r=−0.709; p=0.003), leptin (r=−0.68; p=0.005), and resistin (r=−0.528; p<0.05). In Group B, negative correlations occurred between creatinine and VAI (r=−0.332; p<0.05), BAI (r=−0.619; p<0.0001), leptin (r=−0.676; p<0.0001), and adiponectin (r=−0.423; p=0.002), and between eGFR and resistin (r=−0.276; p<0.05). Conclusions BAI may be a valuable obesity parameter as a predictor of early stages of CKD in patients with obesity. Leptin may be an important pathogenic factor in obese patients with early stages of CKD. Resistin is associated with eGFR in obese patients, independently of CKD. PMID:24280776

  4. Diabetes, gallbladder disease, obesity, and hypertension among Hispanics in New Mexico.

    PubMed

    Samet, J M; Coultas, D B; Howard, C A; Skipper, B J; Hanis, C L

    1988-12-01

    Because Hispanics in the Southwest are genetically admixed with American Indians, the hypothesis has been advanced that the excess occurrence of diabetes mellitus, obesity, and gallbladder disease in this ethnic group may be genetic in origin and results from genes derived from American Indians. This report describes the prevalence of these diseases in 1,175 adult Hispanic participants in a survey of a New Mexico community conducted in 1984-1985. At nearly all ages, the majority of subjects had a body mass index of 25 kg/m2 or greater, and a substantial proportion exceeded 30 kg/m2. The prevalence of obesity was much greater in these Hispanics than is shown in nationwide data for US whites. Diabetes mellitus was also reported more often by Hispanic subjects in this survey than by US whites nationwide. A report of gallbladder trouble or of gallbladder removal was common in both males and females; the prevalence of gallbladder removal was as high in this population as in Mexican Americans previously studied in Starr County, Texas. In spite of the high prevalence of obesity, hypertension was less frequent among the New Mexico Hispanics than is shown in nationwide data for US whites. These findings complement those of previous surveys in Texas, which have shown a notably high proportion of adults to be obese, to have non-insulin-dependent diabetes mellitus, and to have gallbladder disease. The similar epidemiology of these diseases in the Hispanics of New Mexico and the Mexican Americans of Texas supports the hypothesis that American Indian admixture underlies the development of these conditions in Hispanics throughout the Southwest. PMID:3195569

  5. Type 2 diabetes, but not obesity, prevalence is positively associated with ambient temperature.

    PubMed

    Speakman, John R; Heidari-Bakavoli, Sahar

    2016-01-01

    Cold exposure stimulates energy expenditure and glucose disposal. If these factors play a significant role in whole body energy balance, and glucose homeostasis, it is predicted that both obesity and type 2 diabetes prevalence would be lower where it is colder. Previous studies have noted connections between ambient temperature and obesity, but the direction of the effect is confused. No previous studies have explored the link of type 2 diabetes to ambient temperature. We used county level data for obesity and diabetes prevalence across the mainland USA and matched this to county level ambient temperature data. Average ambient temperature explained 5.7% of the spatial variation in obesity and 29.6% of the spatial variation in type 2 diabetes prevalence. Correcting the type 2 diabetes data for the effect of obesity reduced the explained variation to 26.8%. Even when correcting for obesity, poverty and race, ambient temperature explained 12.4% of the variation in the prevalence of type 2 diabetes, and this significant effect remained when latitude was entered into the model as a predictor. When obesity prevalence was corrected for poverty and race the significant effect of temperature disappeared. Enhancing energy expenditure by cold exposure will likely not impact obesity significantly, but may be useful to combat type 2 diabetes. PMID:27477955

  6. Type 2 diabetes, but not obesity, prevalence is positively associated with ambient temperature

    PubMed Central

    Speakman, John R.; Heidari-Bakavoli, Sahar

    2016-01-01

    Cold exposure stimulates energy expenditure and glucose disposal. If these factors play a significant role in whole body energy balance, and glucose homeostasis, it is predicted that both obesity and type 2 diabetes prevalence would be lower where it is colder. Previous studies have noted connections between ambient temperature and obesity, but the direction of the effect is confused. No previous studies have explored the link of type 2 diabetes to ambient temperature. We used county level data for obesity and diabetes prevalence across the mainland USA and matched this to county level ambient temperature data. Average ambient temperature explained 5.7% of the spatial variation in obesity and 29.6% of the spatial variation in type 2 diabetes prevalence. Correcting the type 2 diabetes data for the effect of obesity reduced the explained variation to 26.8%. Even when correcting for obesity, poverty and race, ambient temperature explained 12.4% of the variation in the prevalence of type 2 diabetes, and this significant effect remained when latitude was entered into the model as a predictor. When obesity prevalence was corrected for poverty and race the significant effect of temperature disappeared. Enhancing energy expenditure by cold exposure will likely not impact obesity significantly, but may be useful to combat type 2 diabetes. PMID:27477955

  7. Diabetes and Altered Glucose Metabolism with Aging

    PubMed Central

    Kalyani, Rita Rastogi; Egan, Josephine M.

    2013-01-01

    I. Synopsis Diabetes and impaired glucose tolerance affect a substantial proportion of older adults. While the aging process can be associated with alterations in glucose metabolism, including both relative insulin resistance and islet cell dysfunction, abnormal glucose metabolism is not a necessary component of aging. Instead, older adults with diabetes and altered glucose status likely represent a vulnerable subset of the population at high-risk for complications and adverse geriatric syndromes such as accelerated muscle loss, functional disability, frailty, and early mortality. Goals for treatment of diabetes in the elderly include control of hyperglycemia, prevention and treatment of diabetic complications, avoidance of hypoglycemia and preservation of quality of life. Given the heterogeneity of the elderly population with regards to the presence of comorbidities, life expectancy, and functional status, an individualized approach to diabetes management is often appropriate. A growing area of research seeks to explore associations of dysglycemia and insulin resistance with the development of adverse outcomes in the elderly and may ultimately inform guidelines on the use of future glucose-lowering therapies in this population. PMID:23702405

  8. Obese and diabetic patients with end-stage renal disease: Peritoneal dialysis or hemodialysis?

    PubMed

    Ekart, Robert; Hojs, Radovan

    2016-07-01

    Obesity is a chronic disease that is increasingly prevalent around the world and is a well-recognized risk factor for type 2 diabetes and hypertension, leading causes of end-stage renal disease (ESRD). The obese diabetic patient with ESRD is a challenge for the nephrologist with regard to the type of renal replacement therapy that should be suggested and offered to the patient. There is no evidence that either peritoneal dialysis or hemodialysis is contraindicated in obese ESRD patients. In the literature, we can find a discrepancy in the impact of obesity on mortality among hemodialysis vs. peritoneal dialysis patients. Several studies in hemodialysis patients suggest that a higher BMI confers a survival advantage - the so-called "reverse epidemiology". In contrast, the literature among obese peritoneal dialysis patients is inconsistent, with various studies reporting an increased risk of death, no difference, or a decreased risk of death. Many of these studies only spanned across a few years, and this is probably too short of a time frame for a realistic assessment of obesity's impact on mortality in ESRD patients. The decision for dialysis modality in an obese diabetic patient with ESRD should be individualized. According to the results of published studies, we cannot suggest PD or HD as a better solution for all obese diabetic patients. The obese patient should be educated about all their dialysis options, including home dialysis therapies. In this review, the available literature related to the dialysis modality in obese patients with diabetes and ESRD was reviewed.

  9. Minireview: Epigenetics of obesity and diabetes in humans.

    PubMed

    Slomko, Howard; Heo, Hye J; Einstein, Francine H

    2012-03-01

    Understanding the determinants of human health and disease is overwhelmingly complex, particularly for common, late-onset, chronic disorders, such as obesity and diabetes. Elucidating the genetic and environmental factors that influence susceptibility to disruptions in energy homeostasis and metabolic regulation remain a challenge, and progress will entail the integration of multiple assessments of temporally dynamic environmental exposures in the context of each individual's genotype. To meet this challenge, researchers are increasingly exploring the epigenome, which is the malleable interface of gene-environment interactions. Epigenetic variation, whether innate or induced, contributes to variation in gene expression, the range of potential individual responses to internal and external cues, and risk for metabolic disease. Ultimately, advancement in our understanding of chronic disease susceptibility in humans will depend on refinement of exposure assessment tools and systems biology approaches to interpretation. In this review, we present recent progress in epigenetics of human obesity and diabetes, existing challenges, and the potential for new approaches to unravel the complex biology of metabolic dysregulation.

  10. Sugar, uric acid, and the etiology of diabetes and obesity.

    PubMed

    Johnson, Richard J; Nakagawa, Takahiko; Sanchez-Lozada, L Gabriela; Shafiu, Mohamed; Sundaram, Shikha; Le, Myphuong; Ishimoto, Takuji; Sautin, Yuri Y; Lanaspa, Miguel A

    2013-10-01

    The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that "a calorie is just a calorie" and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.

  11. Sugar, uric acid, and the etiology of diabetes and obesity.

    PubMed

    Johnson, Richard J; Nakagawa, Takahiko; Sanchez-Lozada, L Gabriela; Shafiu, Mohamed; Sundaram, Shikha; Le, Myphuong; Ishimoto, Takuji; Sautin, Yuri Y; Lanaspa, Miguel A

    2013-10-01

    The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that "a calorie is just a calorie" and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease. PMID:24065788

  12. Minireview: Epigenetics of Obesity and Diabetes in Humans

    PubMed Central

    Slomko, Howard; Heo, Hye J.

    2012-01-01

    Understanding the determinants of human health and disease is overwhelmingly complex, particularly for common, late-onset, chronic disorders, such as obesity and diabetes. Elucidating the genetic and environmental factors that influence susceptibility to disruptions in energy homeostasis and metabolic regulation remain a challenge, and progress will entail the integration of multiple assessments of temporally dynamic environmental exposures in the context of each individual's genotype. To meet this challenge, researchers are increasingly exploring the epigenome, which is the malleable interface of gene-environment interactions. Epigenetic variation, whether innate or induced, contributes to variation in gene expression, the range of potential individual responses to internal and external cues, and risk for metabolic disease. Ultimately, advancement in our understanding of chronic disease susceptibility in humans will depend on refinement of exposure assessment tools and systems biology approaches to interpretation. In this review, we present recent progress in epigenetics of human obesity and diabetes, existing challenges, and the potential for new approaches to unravel the complex biology of metabolic dysregulation. PMID:22253427

  13. Sugar, Uric Acid, and the Etiology of Diabetes and Obesity

    PubMed Central

    Johnson, Richard J.; Nakagawa, Takahiko; Sanchez-Lozada, L. Gabriela; Shafiu, Mohamed; Sundaram, Shikha; Le, Myphuong; Ishimoto, Takuji; Sautin, Yuri Y.; Lanaspa, Miguel A.

    2013-01-01

    The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease. PMID:24065788

  14. Effects of a Culturally Grounded Community-Based Diabetes Prevention Program for Obese Latino Adolescents

    PubMed Central

    Shaibi, Gabriel Q.; Konopken, Yolanda; Hoppin, Erica; Keller, Colleen S.; Ortega, Rocio; Castro, Felipe González

    2012-01-01

    Purpose The purpose of this study was to test the feasibility and preliminary effects of a culturally grounded, community-based diabetes prevention program among obese Latino adolescents. Methods Fifteen obese Latino adolescents (body mass index [BMI] percentile = 96.3 ± 1.1, age = 15.0 ± 0.9 years) completed a 12-week intervention that included weekly lifestyle education classes delivered by bilingual/bicultural promotoras and three, 60-minute physical activity sessions per week. Participants were assessed for anthropometrics (height, weight, BMI, and waist circumference), cardiorespiratory fitness, physical activity/inactivity, nutrition behaviors, and insulin sensitivity and glucose tolerance by a 2-hour oral glucose tolerance test. Results The intervention resulted in significant decreases in BMI z score, BMI percentile, and waist circumference; increases in cardiorespiratory fitness; and decreases in physical inactivity and dietary fat consumption. In addition to these changes, the intervention led to significant improvements in insulin sensitivity and reductions in 2-hour glucose levels. Conclusions These results support the feasibility and efficacy of a community-based diabetes prevention program for high-risk Latino youth. Translational approaches that are both culturally grounded and biologically meaningful represent a novel and innovative strategy for closing the obesity-related health disparities gap. PMID:22585870

  15. A look inside the diabetic brain: Contributors to diabetes-induced brain aging.

    PubMed

    Wrighten, Shayna A; Piroli, Gerardo G; Grillo, Claudia A; Reagan, Lawrence P

    2009-05-01

    Central nervous system (CNS) complications resulting from diabetes is a problem that is gaining more acceptance and attention. Recent evidence suggests morphological, electrophysiological and cognitive changes, often observed in the hippocampus, in diabetic individuals. Many of the CNS changes observed in diabetic patients and animal models of diabetes are reminiscent of the changes seen in normal aging. The central commonalities between diabetes-induced and age-related CNS changes have led to the theory of advanced brain aging in diabetic patients. This review summarizes the findings of the literature as they relate to the relationship between diabetes and dementia and discusses some of the potential contributors to diabetes-induced CNS impairments.

  16. Role of the Gut Microbiome in Obesity and Diabetes Mellitus.

    PubMed

    Barlow, Gillian M; Yu, Allen; Mathur, Ruchi

    2015-12-01

    Type 2 diabetes mellitus (T2DM) and obesity represent two of the biggest global health challenges of this century and are associated with significant comorbidities and healthcare costs. Although multiple factors undoubtedly contribute to the development and progression of DM and obesity, research over the last decade has demonstrated that the microbes that colonize the human gut may play key contributory roles. Gut microbes are now known to codevelop with the human host and are strongly influenced by mode of birth and early diet and nutrition, as well as environmental and other factors including antibiotic exposure. Gut microbes contribute to human health through roles in polysaccharide breakdown, nutrient absorption, inflammatory responses, gut permeability, and bile acid modification. Numerous studies have suggested that disruptions in the relative proportions of gut microbial populations may contribute to weight gain and insulin resistance, including alterations in Gammaproteobacteria and Verrucomicrobia and the ratios of Firmicutes to Bacteroidetes in weight gain and possible alterations in butyrate-producing bacteria such as Faecalibacterium prausnitzii in DM. In addition, it has been shown that the methanogenic Archaea may contribute to altered metabolism and weight gain in the host. However, the majority of studies are performed with stool or colonic samples and may not be representative of the metabolically active small intestine. Studies predominantly in rodent models are beginning to elucidate the mechanisms by which gut microbes contribute to DM and obesity, but much remains to be learned before we can begin to approach targeted treatments.

  17. Regional variation in the prevalence of overweight/obesity, hypertension and diabetes and their correlates among the adult rural population in India.

    PubMed

    Meshram, I I; Vishnu Vardhana Rao, M; Sudershan Rao, V; Laxmaiah, A; Polasa, K

    2016-04-14

    A community-based, cross-sectional study was carried out in five regions of India by adopting a multistage random sampling procedure. Information was collected from the participants about socio-demographic particulars such as age, sex, occupation, education, etc. Anthropometric measurements such as height, weight and waist and hip circumferences were measured and three measurements of blood pressure were obtained. Fasting blood sugar was assessed using a Glucometer. Data analysis was done using descriptive statistics, χ(2) test for association and logistic regression analysis. A total of 7531 subjects were covered for anthropometry and blood pressure. The overall prevalence of overweight/obesity and abdominal obesity was 29 and 21%, respectively, and was higher in the Southern region (40% each) as compared with other regions. The prevalence of hypertension was 18 and 16% and diabetes was 9·5% each among men and women, respectively. The risk of hypertension and diabetes was significantly higher among adults from the Southern and Western regions, the among elderly, among overweight/obese individuals and those with abdominal obesity. In conclusion, the prevalence of overweight/obesity and hypertension was higher in the Southern region, whereas diabetes was higher in the Southern and Western regions. Factors such as increasing age, male sex, overweight/obesity, and abdominal obesity were important risk factors for hypertension and diabetes. Appropriate health and nutrition education should be given to the community to control these problems. PMID:26867590

  18. Regional variation in the prevalence of overweight/obesity, hypertension and diabetes and their correlates among the adult rural population in India.

    PubMed

    Meshram, I I; Vishnu Vardhana Rao, M; Sudershan Rao, V; Laxmaiah, A; Polasa, K

    2016-04-14

    A community-based, cross-sectional study was carried out in five regions of India by adopting a multistage random sampling procedure. Information was collected from the participants about socio-demographic particulars such as age, sex, occupation, education, etc. Anthropometric measurements such as height, weight and waist and hip circumferences were measured and three measurements of blood pressure were obtained. Fasting blood sugar was assessed using a Glucometer. Data analysis was done using descriptive statistics, χ(2) test for association and logistic regression analysis. A total of 7531 subjects were covered for anthropometry and blood pressure. The overall prevalence of overweight/obesity and abdominal obesity was 29 and 21%, respectively, and was higher in the Southern region (40% each) as compared with other regions. The prevalence of hypertension was 18 and 16% and diabetes was 9·5% each among men and women, respectively. The risk of hypertension and diabetes was significantly higher among adults from the Southern and Western regions, the among elderly, among overweight/obese individuals and those with abdominal obesity. In conclusion, the prevalence of overweight/obesity and hypertension was higher in the Southern region, whereas diabetes was higher in the Southern and Western regions. Factors such as increasing age, male sex, overweight/obesity, and abdominal obesity were important risk factors for hypertension and diabetes. Appropriate health and nutrition education should be given to the community to control these problems.

  19. The compliance of hypocaloric diet in type 2 diabetic obese patients: a brief-term study.

    PubMed

    Zilli, F; Croci, M; Tufano, A; Caviezel, F

    2000-12-01

    In studies of the effect of diets in obese type 2 diabetic patients, information about the degree of compliance or non-compliance is generally lacking or incomplete, though their poor long-term success rate is widely recognized. We have quantified the degree of short-term compliance with a personalized hypocaloric diet (800-1500 kcal) in 77 obese type 2 diabetic patients (mean age 60, mean BMI 34.4) three months after explaining their dietary schedule and its expected advantages by means of simple but essential nutritional advice lasting about 20 minutes of the type currently used for such patients attending diabetes care institutions or outpatient departments. Even though a mean 14% reduction in daily food intake was achieved, the mean daily energy intake at the interview (assessed by means of the 3-day recall method) still exceeded the prescribed diet by 40-50%. The worst compliance in terms of total excess energy intake or carbohydrate and fat intake was found in the older patients. The greater the excess of food intake, the poorer the metabolic control, as expected.

  20. Changing patterns of hypertension, diabetes, obesity and diet among Melanesians and Micronesians in the Solomon Islands.

    PubMed

    Eason, R J; Pada, J; Wallace, R; Henry, A; Thornton, R

    1987-05-01

    A cross-sectional survey of diabetes, hypertension, obesity and dietary patterns has been conducted in the Western Province of the Solomon Islands. Three groups--traditional and more urbanized Melanesians and semitraditional Micronesians--were compared. Abnormal glucose tolerance was rare (less than 1% over all) in Melanesians regardless of acculturation, but was present in 9.7% of adult Micronesians in whom it was associated with age; obesity; female sex; and a diet that was high in energy and refined carbohydrates. Hypertension, which was associated with advancing age and obesity, was recorded in 6.0% and 8.3% of traditional and partly urbanized Melanesians, respectively, and in 4.8% of Micronesians. Systolic and diastolic blood pressures correlated significantly with age for all except traditional Melanesian women among whom the association was limited to the systolic blood pressure only. Significant correlation coefficients were recorded between diastolic blood pressure and body mass index for both sexes and all groups, and between systolic blood pressure and body mass index for all women but only for Micronesian men. Dramatic differences in life-style and dietary patterns are described for rural and more urbanized Melanesians among whom the mean daily urinary sodium outputs were 67 and 119 mmol/L, respectively. PMID:3497330

  1. Changes in the Growth Hormone-IGF-I Axis in Non-obese Diabetic Mice

    PubMed Central

    Segev, Yael; Eshet, Rina; Flyvbjerg, Allan; Phillip, Moshe

    2000-01-01

    We investigated the changes in GH-IGF-I axis in non-obese diabetic (NOD)-mice, a model of insulin dependent diabetes mellitus. Diabetic female NOD mice and their age- and sex-matched controls were sacrificed at 4, 14, 21 and 30 days (30d DM) after the onset of glycosuria. Serum GH levels increased and serum IGF-I levels decreased in the 30d DM group (182 ± 32% and 45 ± 24% of age-matched controls respectively, p < 0.05). Another group (30d DM + I) was given SC insulin, and its serum IGF-I levels remained decreased. Liver GH receptor (GHR) and GH binding protein (GHBP) mRNA levels, as well as liver membrane GH binding assays were deeply decreased in the 30d DM group in comparison to controls. GHR message and binding capacity remained decreased in the 30d DM + I group. Renal GHR mRNA was decreased at 21d DM but not at 14d DM, whereas GHBP mRNA remained unchanged throughout the experiment. In conclusion, increased serum GH levels are documented in NOD diabetic mice, similarly to the changes described in humans. The decrease in GHR levels and decreased serum IGF-I in spite of increased circulating GH suggest a state of GH resistance. PMID:11469393

  2. [Role of vitamin D and calcium in obesity and type 2 diabetes].

    PubMed

    Kuroda, Masashi; Sakaue, Hiroshi

    2016-03-01

    Obesity, induced by unhealthy lifestyle choices, could be involved in the development of chronic diseases like type 2 diabete. Obesity is largely due to the imbalance of energy intake and expenditure, therefore we have put more emphasis on the amount of macronutrients including carbohydrates, fats and proteins as dietary therapy for obesity and related-conditions. On the other hand, several studies revealed obese or diabetic patients were more likely to have micronutrient deficiencies such as vitamins and minerals. Besides the effects on bone metabolism, vitamin D and calcium might contribute to metabolic disorder accompanied by obesity. However, it has not been concluded supplementation of these two nutrients has a benefit in obese or diabetic individuals. Further studies are needed. PMID:26923970

  3. Bioinformatic analysis of functional proteins involved in obesity associated with diabetes.

    PubMed

    Rao, Allam Appa; Tayaru, N Manga; Thota, Hanuman; Changalasetty, Suresh Babu; Thota, Lalitha Saroja; Gedela, Srinubabu

    2008-03-01

    The twin epidemic of diabetes and obesity pose daunting challenges worldwide. The dramatic rise in obesity-associated diabetes resulted in an alarming increase in the incidence and prevalence of obesity an important complication of diabetes. Differences among individuals in their susceptibility to both these conditions probably reflect their genetic constitutions. The dramatic improvements in genomic and bioinformatic resources are accelerating the pace of gene discovery. It is tempting to speculate the key susceptible genes/proteins that bridges diabetes mellitus and obesity. In this regard, we evaluated the role of several genes/proteins that are believed to be involved in the evolution of obesity associated diabetes by employing multiple sequence alignment using ClustalW tool and constructed a phylogram tree using functional protein sequences extracted from NCBI. Phylogram was constructed using Neighbor-Joining Algorithm a bioinformatic tool. Our bioinformatic analysis reports resistin gene as ominous link with obesity associated diabetes. This bioinformatic study will be useful for future studies towards therapeutic inventions of obesity associated type 2 diabetes. PMID:23675069

  4. Inverse associations between obesity indicators and thymic T-cell production levels in aging atomic-bomb survivors.

    PubMed

    Yoshida, Kengo; Nakashima, Eiji; Kubo, Yoshiko; Yamaoka, Mika; Kajimura, Junko; Kyoizumi, Seishi; Hayashi, Tomonori; Ohishi, Waka; Kusunoki, Yoichiro

    2014-01-01

    Reduction of the naive T-cell population represents a deteriorating state in the immune system that occurs with advancing age. In animal model studies, obesity compromises the T-cell immune system as a result of enhanced adipogenesis in primary lymphoid organs and systemic inflammation. In this study, to test the hypothesis that obesity may contribute to the aging of human T-cell immunity, a thousand atomic-bomb survivors were examined for obesity status and ability to produce naive T cells, i.e., T-cell receptor excision circle (TREC) numbers in CD4 and CD8 T cells. The number of TRECs showed a strong positive correlation with naive T cell numbers, and lower TREC numbers were associated with higher age. We found that the TREC number was inversely associated with levels of obesity indicators (BMI, hemoglobin A1c) and serum CRP levels. Development of type-2 diabetes and fatty liver was also associated with lower TREC numbers. This population study suggests that obesity with enhanced inflammation is involved in aging of the human T-cell immune system. Given the fact that obesity increases the risk of numerous age-related diseases, attenuated immune competence is a possible mechanistic link between obesity and disease development among the elderly.

  5. Inverse associations between obesity indicators and thymic T-cell production levels in aging atomic-bomb survivors.

    PubMed

    Yoshida, Kengo; Nakashima, Eiji; Kubo, Yoshiko; Yamaoka, Mika; Kajimura, Junko; Kyoizumi, Seishi; Hayashi, Tomonori; Ohishi, Waka; Kusunoki, Yoichiro

    2014-01-01

    Reduction of the naive T-cell population represents a deteriorating state in the immune system that occurs with advancing age. In animal model studies, obesity compromises the T-cell immune system as a result of enhanced adipogenesis in primary lymphoid organs and systemic inflammation. In this study, to test the hypothesis that obesity may contribute to the aging of human T-cell immunity, a thousand atomic-bomb survivors were examined for obesity status and ability to produce naive T cells, i.e., T-cell receptor excision circle (TREC) numbers in CD4 and CD8 T cells. The number of TRECs showed a strong positive correlation with naive T cell numbers, and lower TREC numbers were associated with higher age. We found that the TREC number was inversely associated with levels of obesity indicators (BMI, hemoglobin A1c) and serum CRP levels. Development of type-2 diabetes and fatty liver was also associated with lower TREC numbers. This population study suggests that obesity with enhanced inflammation is involved in aging of the human T-cell immune system. Given the fact that obesity increases the risk of numerous age-related diseases, attenuated immune competence is a possible mechanistic link between obesity and disease development among the elderly. PMID:24651652

  6. Inverse Associations between Obesity Indicators and Thymic T-Cell Production Levels in Aging Atomic-Bomb Survivors

    PubMed Central

    Yoshida, Kengo; Nakashima, Eiji; Kubo, Yoshiko; Yamaoka, Mika; Kajimura, Junko; Kyoizumi, Seishi; Hayashi, Tomonori; Ohishi, Waka; Kusunoki, Yoichiro

    2014-01-01

    Reduction of the naive T-cell population represents a deteriorating state in the immune system that occurs with advancing age. In animal model studies, obesity compromises the T-cell immune system as a result of enhanced adipogenesis in primary lymphoid organs and systemic inflammation. In this study, to test the hypothesis that obesity may contribute to the aging of human T-cell immunity, a thousand atomic-bomb survivors were examined for obesity status and ability to produce naive T cells, i.e., T-cell receptor excision circle (TREC) numbers in CD4 and CD8 T cells. The number of TRECs showed a strong positive correlation with naive T cell numbers, and lower TREC numbers were associated with higher age. We found that the TREC number was inversely associated with levels of obesity indicators (BMI, hemoglobin A1c) and serum CRP levels. Development of type-2 diabetes and fatty liver was also associated with lower TREC numbers. This population study suggests that obesity with enhanced inflammation is involved in aging of the human T-cell immune system. Given the fact that obesity increases the risk of numerous age-related diseases, attenuated immune competence is a possible mechanistic link between obesity and disease development among the elderly. PMID:24651652

  7. Obesity and Type 2 Diabetes: What Can Be Unified and What Needs to Be Individualized?

    PubMed Central

    Ferrannini, Ele; Goldfine, Allison B.; Nathan, David M.; Schwartz, Michael W.; Smith, Robert J.; Smith, Steven R.

    2011-01-01

    Objective: This report examines what is known about the relationship between obesity and type 2 diabetes and how future research in these areas might be directed to benefit prevention, interventions, and overall patient care. Research Design and Methods: An international working group of 32 experts in the pathophysiology, genetics, clinical trials, and clinical care of obesity and/or type 2 diabetes participated in a conference held on 6–7 January 2011 and cosponsored by The Endocrine Society, the American Diabetes Association, and the European Association for the Study of Diabetes. A writing group comprising eight participants subsequently prepared this summary and recommendations. Participants reviewed and discussed published literature and their own unpublished data. Results: The writing group unanimously supported the summary and recommendations as representing the working group's majority or unanimous opinions. Conclusions: The major questions linking obesity to type 2 diabetes that need to be addressed by combined basic, clinical, and population-based scientific approaches include the following: 1) Why do not all patients with obesity develop type 2 diabetes? 2) Through what mechanisms do obesity and insulin resistance contribute to β-cell decompensation, and if/when obesity prevention ensues, how much reduction in type 2 diabetes incidence will follow? 3) How does the duration of type 2 diabetes relate to the benefits of weight reduction by lifestyle, weight-loss drugs, and/or bariatric surgery on β-cell function and glycemia? 4) What is necessary for regulatory approval of medications and possibly surgical approaches for preventing type 2 diabetes in patients with obesity? Improved understanding of how obesity relates to type 2 diabetes may help advance effective and cost-effective interventions for both conditions, including more tailored therapy. To expedite this process, we recommend further investigation into the pathogenesis of these coexistent

  8. Obesity and Type 2 Diabetes: What Can Be Unified and What Needs to Be Individualized?

    PubMed Central

    Ferrannini, Ele; Goldfine, Allison B.; Nathan, David M.; Schwartz, Michael W.; Smith, Robert J.; Smith, Steven R.

    2011-01-01

    OBJECTIVE This report examines what is known about the relationship between obesity and type 2 diabetes and how future research in these areas might be directed to benefit prevention, interventions, and overall patient care. RESEARCH DESIGN AND METHODS An international working group of 32 experts in the pathophysiology, genetics, clinical trials, and clinical care of obesity and/or type 2 diabetes participated in a conference held on 6–7 January 2011 and cosponsored by The Endocrine Society, the American Diabetes Association, and the European Association for the Study of Diabetes. A writing group comprising eight participants subsequently prepared this summary and recommendations. Participants reviewed and discussed published literature and their own unpublished data. RESULTS The writing group unanimously supported the summary and recommendations as representing the working group's majority or unanimous opinions. CONCLUSIONS The major questions linking obesity to type 2 diabetes that need to be addressed by combined basic, clinical, and population-based scientific approaches include the following: 1) Why do not all patients with obesity develop type 2 diabetes? 2) Through what mechanisms do obesity and insulin resistance contribute to β-cell decompensation, and if/when obesity prevention ensues, how much reduction in type 2 diabetes incidence will follow? 3) How does the duration of type 2 diabetes relate to the benefits of weight reduction by lifestyle, weight-loss drugs, and/or bariatric surgery on β-cell function and glycemia? 4) What is necessary for regulatory approval of medications and possibly surgical approaches for preventing type 2 diabetes in patients with obesity? Improved understanding of how obesity relates to type 2 diabetes may help advance effective and cost-effective interventions for both conditions, including more tailored therapy. To expedite this process, we recommend further investigation into the pathogenesis of these coexistent

  9. Neighborhoods, Obesity, and Diabetes — A Randomized Social Experiment

    PubMed Central

    Ludwig, Jens; Sanbonmatsu, Lisa; Gennetian, Lisa; Adam, Emma; Duncan, Greg J.; Katz, Lawrence F.; Kessler, Ronald C.; Kling, Jeffrey R.; Lindau, Stacy Tessler; Whitaker, Robert C.; McDade, Thomas W.

    2012-01-01

    BACKGROUND The question of whether neighborhood environment contributes directly to the development of obesity and diabetes remains unresolved. The study reported on here uses data from a social experiment to assess the association of randomly assigned variation in neighborhood conditions with obesity and diabetes. METHODS From 1994 through 1998, the Department of Housing and Urban Development (HUD) randomly assigned 4498 women with children living in public housing in high-poverty urban census tracts (in which ≥40% of residents had incomes below the federal poverty threshold) to one of three groups: 1788 were assigned to receive housing vouchers, which were redeemable only if they moved to a low-poverty census tract (where <10% of residents were poor), and counseling on moving; 1312 were assigned to receive unrestricted, traditional vouchers, with no special counseling on moving; and 1398 were assigned to a control group that was offered neither of these opportunities. From 2008 through 2010, as part of a long-term follow-up survey, we measured data indicating health outcomes, including height, weight, and level of glycated hemoglobin (HbA1c). RESULTS As part of our long-term survey, we obtained data on body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) for 84.2% of participants and data on glycated hemoglobin level for 71.3% of participants. Response rates were similar across randomized groups. The prevalences of a BMI of 35 or more, a BMI of 40 or more, and a glycated hemoglobin level of 6.5% or more were lower in the group receiving the low-poverty vouchers than in the control group, with an absolute difference of 4.61 percentage points (95% confidence interval [CI], −8.54 to −0.69), 3.38 percentage points (95% CI, −6.39 to −0.36), and 4.31 percentage points (95% CI, −7.82 to −0.80), respectively. The differences between the group receiving traditional vouchers and the control group were not significant

  10. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    SciTech Connect

    Wang, Jun; Cao, Hui; Wang, Hongjie; Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli; Xiang, Ming

    2015-06-15

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

  11. Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

    PubMed

    Akhtar, Muhammad Tayyab; Bin Mohd Sarib, Mohamad Syakir; Ismail, Intan Safinar; Abas, Faridah; Ismail, Amin; Lajis, Nordin Hj; Shaari, Khozirah

    2016-01-01

    Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract. PMID:27517894

  12. Association between impaired fasting glycaemia in pediatric obesity and type 2 diabetes in young adulthood

    PubMed Central

    Hagman, E; Danielsson, P; Brandt, L; Ekbom, A; Marcus, C

    2016-01-01

    Objectives: In adults, impaired fasting glycemia (IFG) increases the risk for type 2 diabetes mellitus (T2DM). This study aimed to investigate to which extent children with obesity develop T2DM during early adulthood, and to determine whether IFG and elevated hemoglobin A1c (HbA1c) in obese children are risk markers for early development of T2DM. Methods: In this prospective cohort study, 1620 subjects from the Swedish Childhood Obesity Treatment Registry – BORIS who were ⩾18 years at follow-up and 8046 individuals in a population-based comparison group, matched on gender age and living area, were included. IFG was defined according to both ADA (cut-off 5.6 mmol l−1) and WHO (6.1 mmol l−1). Elevated HbA1c was defined according to ADA (cut-off 39 mmol l−1). Main outcome was T2DM medication, as a proxy for T2DM. Data on medications were retrieved from a national registry. Results: The childhood obesity cohort were 24 times more likely to receive T2DM medications in early adulthood compared with the comparison group (95% confidence interval (CI): 12.52–46). WHO-defined IFG predicted future use of T2DM medication with an adjusted hazard ratio (HR) of 3.73 (95% CI: 1.87–7.45) compared with those who had fasting glucose levels <5.6 mmol l−1. A fasting glucose level of 5.6–6.0 mmol l−1, that is, the IFG-interval added by American Diabetes Association (ADA), did not increase the use of T2DM medication more than pediatric obesity itself, adjusted HR=1.72 (0.84–3.52). Elevated levels of HbA1c resulted in an adjusted HR=3.12 (1.50–6.52). More severe degree of obesity also increased the future T2DM risk. CONCLUSION: IFG according to WHO and elevated HbA1c (39–48 mmol l−1), but not the additional fasting glucose interval added by ADA (5.6–6.0 mmol l−1), can be considered as prediabetes in the obese pediatric population in Sweden. PMID:27548712

  13. Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract.

    PubMed

    Mediani, Ahmed; Abas, Faridah; Maulidiani, M; Khatib, Alfi; Tan, Chin Ping; Ismail, Intan Safinar; Shaari, Khozirah; Ismail, Amin; Lajis, N H

    2016-09-01

    Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus. PMID:27318080

  14. Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice.

    PubMed

    Miyazaki, Tsuneyuki; Shirakami, Yohei; Kubota, Masaya; Ideta, Takayasu; Kochi, Takahiro; Sakai, Hiroyasu; Tanaka, Takuji; Moriwaki, Hisataka; Shimizu, Masahito

    2016-03-01

    Obesity and related metabolic abnormalities play a key role in liver carcinogenesis. Non-alcoholic steatohepatitis (NASH), which is often complicated with obesity and diabetes mellitus, is associated with the development of hepatocellular carcinoma (HCC). Sodium alginate (SA), which is extracted from brown seaweeds, is marketed as a weight loss supplement because of its high viscosity and gelling properties. In the present study, we examined the effects of SA on the progression of NASH and related liver carcinogenesis in monosodium glutamate (MSG)-treated mice, which show obesity, diabetes mellitus, and NASH-like histopathological changes. Male MSG-mice were intraperitoneally injected with diethylnitrosamine at 2 weeks of age, and, thereafter, they received a basal diet containing high- or low-molecular-weight SA throughout the experiment (16 weeks). At sacrifice, control MSG-treated mice fed the basal-diet showed significant obesity, hyperinsulinemia, steatosis and hepatic tumor development. SA administration suppressed body weight gain; improved insulin sensitivity, hyperinsulinemia, and hyperleptinemia; attenuated inflammation in the liver and white adipose tissue; and inhibited hepatic lipogenesis and progression of NASH. SA also reduced oxidative stress and increased anti-oxidant enzyme levels in the liver. Development of hepatic tumors, including liver cell adenoma and HCC, and hepatic pre-neoplastic lesions was significantly inhibited by SA supplementation. In conclusion, oral SA supplementation improves liver steatosis, insulin resistance, chronic inflammation, and oxidative stress, preventing the development of liver tumorigenesis in obese and diabetic mice. SA may have ability to suppress steatosis-related liver carcinogenesis in obese and diabetic subjects. PMID:26871288

  15. Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice

    PubMed Central

    Miyazaki, Tsuneyuki; Shirakami, Yohei; Kubota, Masaya; Ideta, Takayasu; Kochi, Takahiro; Sakai, Hiroyasu; Tanaka, Takuji; Moriwaki, Hisataka; Shimizu, Masahito

    2016-01-01

    Obesity and related metabolic abnormalities play a key role in liver carcinogenesis. Non-alcoholic steatohepatitis (NASH), which is often complicated with obesity and diabetes mellitus, is associated with the development of hepatocellular carcinoma (HCC). Sodium alginate (SA), which is extracted from brown seaweeds, is marketed as a weight loss supplement because of its high viscosity and gelling properties. In the present study, we examined the effects of SA on the progression of NASH and related liver carcinogenesis in monosodium glutamate (MSG)-treated mice, which show obesity, diabetes mellitus, and NASH-like histopathological changes. Male MSG-mice were intraperitoneally injected with diethylnitrosamine at 2 weeks of age, and, thereafter, they received a basal diet containing high- or low-molecular-weight SA throughout the experiment (16 weeks). At sacrifice, control MSG-treated mice fed the basal-diet showed significant obesity, hyperinsulinemia, steatosis and hepatic tumor development. SA administration suppressed body weight gain; improved insulin sensitivity, hyperinsulinemia, and hyperleptinemia; attenuated inflammation in the liver and white adipose tissue; and inhibited hepatic lipogenesis and progression of NASH. SA also reduced oxidative stress and increased anti-oxidant enzyme levels in the liver. Development of hepatic tumors, including liver cell adenoma and HCC, and hepatic pre-neoplastic lesions was significantly inhibited by SA supplementation. In conclusion, oral SA supplementation improves liver steatosis, insulin resistance, chronic inflammation, and oxidative stress, preventing the development of liver tumorigenesis in obese and diabetic mice. SA may have ability to suppress steatosis-related liver carcinogenesis in obese and diabetic subjects. PMID:26871288

  16. Obesity, albuminuria and hypertension among Hong Kong Chinese with non-insulin-dependent diabetes mellitus (NIDDM).

    PubMed Central

    Chan, J. C.; Cheung, C. K.; Swaminathan, R.; Nicholls, M. G.; Cockram, C. S.

    1993-01-01

    A total of 412 Hong Kong Chinese diabetic patients were studied on at least two occasions 8-16 weeks apart. Although 28% were insulin-treated, only 3.6% had insulin-dependent diabetes (IDDM). In the remaining 397 patients with non-insulin-dependent diabetes (NIDDM), the mean (s.d.) body mass index (BMI) was 24.4 +/- 3.2 kg/m2 in females and 24.2 +/- 3.2 kg/m2 in males. Obesity was present in 17% of males (BMI > 27 kg/m2) and 40% of females (BMI > 25 kg/m2). Established hypertension was present in 49%. Abnormal albuminuria, defined as a mean urinary albumin/creatinine (UA/Cr) ratio greater than 5.4 mg/mmol based on two random spot urine samples, was present in 47%. On stepwise multiple regression analysis, UA/Cr ratio (R2 = 0.34, F = 65.4, P < 0.001) showed significant associations with systolic blood pressure (standardized regression coefficient beta = 0.40, P < 0.001), plasma creatinine concentration (beta = 0.27, P < 0.001) and glycosylated haemoglobin (beta = 0.20, P < 0.001). While the prevalence of hypertension increased with increasing severity of proteinuria, 40% of normoalbuminuric patients had hypertension. Among patients diagnosed before the age of 35 (n = 67), 52% were insulin-treated although only 10% were insulin-dependent. Among these NIDDM patients of young onset (n = 59), obesity was present in 25% of males and 56% of females. Overall, 18% of these patients had a blood pressure greater than 140/90 mmHg and 27% had abnormal albuminuria. In Hong Kong Chinese, diabetes mellitus is predominantly non-insulin-dependent even in the young. Obesity is more prevalent among females. Abnormal albuminuria is relatively common and is closely associated with hypertension and glycaemic control. In the light of increasing prevalence of diabetes among overseas Chinese, our findings may have important implications in the management of Chinese diabetic patients. PMID:8497435

  17. Effects of Obesity and Diabetes on α- and β-Cell Mass in Surgically Resected Human Pancreas

    PubMed Central

    Inaishi, Jun; Sato, Seiji; Kou, Kinsei; Murakami, Rie; Watanabe, Yuusuke; Kitago, Minoru; Kitagawa, Yuko; Yamada, Taketo; Itoh, Hiroshi

    2016-01-01

    Context: The ethnic difference in β-cell regenerative capacity in response to obesity may be attributable to different phenotypes of type 2 diabetes among ethnicities. Objective: This study aimed to clarify the effects of diabetes and obesity on β- (BCM) and α-cell mass (ACM) in the Japanese population. Design, Setting, and Participants: We obtained the pancreases of 99 individuals who underwent pancreatic surgery and whose resected pancreas sample contained adequate normal pancreas for histological analysis. Questionnaires on a family history of diabetes and history of obesity were conducted in 59 patients. Pancreatic sections were stained for insulin or glucagon, and fractional β- and α-cell area were measured. Islet size and density as well as β-cell turnover were also quantified. Results: In patients with diabetes, BCM was decreased by 46% compared with age- and body mass index-matched nondiabetic patients (1.48% ± 1.08% vs 0.80% ± 0.54%, P < .001), whereas there was no difference in ACM between the groups. There was no effect of obesity or history of obesity on BCM and ACM irrespective of the presence or absence of diabetes. There was a negative correlation between BCM, but not ACM, and glycated hemoglobin before and after pancreatic surgery. In addition, reduced BCM was observed in patients with pancreatic cancer compared with those with other pancreatic tumors. Conclusions: These findings suggest that the increase in BCM in the face of insulin resistance is extremely limited in the Japanese, and BCM rather than ACM has a major role in regulating blood glucose level in humans. PMID:27070277

  18. Obesity, job satisfaction and disability at older ages in Europe.

    PubMed

    Pagan, Ricardo; de Haro, Carmen Ordóñez; Sánchez, Carlos Rivas

    2016-03-01

    This study investigates the interaction between obesity and disability and its impact on the levels of job satisfaction reported by older workers (aged 50-64) in ten European countries (Denmark, Sweden, Austria, Belgium, France, Germany, The Netherlands, Switzerland, Italy and Spain). Using longitudinal data from the Survey of Health, Ageing and Retirement in Europe for the years 2004, 2007 and 2011, we estimate a job satisfaction equation which includes a set of explanatory variables measuring worker's obesity and disability status (non-disabled, non-limited disabled, and limited disabled). The results show that, after controlling for other variables, obese workers are more likely to be satisfied with their jobs as compared to those workers with normal weight (0.066 points). In addition, being limited disabled or having poor health contribute to reducing (by 0.082 and 0.172 points, respectively) this positive effect of being obese on job satisfaction. However, we do not find any differential effect of obesity on job satisfaction by disability status, except for those underweight individuals who are not limited in their daily activities. Overall, these findings support the hypothesis of lower expectations about jobs for obese workers, especially if they also have poor health. PMID:26656204

  19. Obesity, job satisfaction and disability at older ages in Europe.

    PubMed

    Pagan, Ricardo; de Haro, Carmen Ordóñez; Sánchez, Carlos Rivas

    2016-03-01

    This study investigates the interaction between obesity and disability and its impact on the levels of job satisfaction reported by older workers (aged 50-64) in ten European countries (Denmark, Sweden, Austria, Belgium, France, Germany, The Netherlands, Switzerland, Italy and Spain). Using longitudinal data from the Survey of Health, Ageing and Retirement in Europe for the years 2004, 2007 and 2011, we estimate a job satisfaction equation which includes a set of explanatory variables measuring worker's obesity and disability status (non-disabled, non-limited disabled, and limited disabled). The results show that, after controlling for other variables, obese workers are more likely to be satisfied with their jobs as compared to those workers with normal weight (0.066 points). In addition, being limited disabled or having poor health contribute to reducing (by 0.082 and 0.172 points, respectively) this positive effect of being obese on job satisfaction. However, we do not find any differential effect of obesity on job satisfaction by disability status, except for those underweight individuals who are not limited in their daily activities. Overall, these findings support the hypothesis of lower expectations about jobs for obese workers, especially if they also have poor health.

  20. Evaluation of Obesity in School-Age Children.

    PubMed

    Dobashi, Kazushige

    2016-01-01

    To prevent obesity in middle age, early precautions and interventions are required during childhood. Therefore, it is very important to accurately evaluate the degree of overweight in children. Body mass index (BMI) is widely used worldwide in adults, but not in children. Because standard BMI, which is calculated using the average height and weight for age, changes widely during growth, a constant cut-off point cannot be set for children. An international unified method defining childhood obesity has not been established. In many countries, BMI-for-age percentile (BMI%) value or Z (standard deviation) score is used, whereas in Japan, the percentage of overweight (POW), which is the modified weight-for-height method, is used. We compared BMI% values with POW values obtained using the anthropometric data of elementary and junior high school students based on the Japanese school survey conducted in 2000 and found that the values for the degree of overweight were significantly different between the two methods. It became clear that tall students were easily defined as being overweight, whereas short students tended to be evaluated as being underweight when using BMI%. POW method seemed to be more appropriate than BMI% for school-age children. Abdominal obesity, excess visceral adipose tissue (VAT), is highly associated with obesity-related complications. Waist circumference (WC) is now accepted as an appropriate guide to VAT accumulation. The cut-off value of WC defining excess VAT is 80 cm at the umbilical level in Japanese school-age children. It is not easy to decide the obesity criteria and optimum WC in school-age children. Childhood obesity should be discussed more internationally.

  1. Chlorinated persistent organic pollutants, obesity, and type 2 diabetes.

    PubMed

    Lee, Duk-Hee; Porta, Miquel; Jacobs, David R; Vandenberg, Laura N

    2014-08-01

    Persistent organic pollutants (POPs) are lipophilic compounds that travel with lipids and accumulate mainly in adipose tissue. Recent human evidence links low-dose POPs to an increased risk of type 2 diabetes (T2D). Because humans are contaminated by POP mixtures and POPs possibly have nonmonotonic dose-response relations with T2D, critical methodological issues arise in evaluating human findings. This review summarizes epidemiological results on chlorinated POPs and T2D, and relevant experimental evidence. It also discusses how features of POPs can affect inferences in humans. The evidence as a whole suggests that, rather than a few individual POPs, background exposure to POP mixtures-including organochlorine pesticides and polychlorinated biphenyls-can increase T2D risk in humans. Inconsistent statistical significance for individual POPs may arise due to distributional differences in POP mixtures among populations. Differences in the observed shape of the dose-response curves among human studies may reflect an inverted U-shaped association secondary to mitochondrial dysfunction or endocrine disruption. Finally, we examine the relationship between POPs and obesity. There is evidence in animal studies that low-dose POP mixtures are obesogenic. However, relationships between POPs and obesity in humans have been inconsistent. Adipose tissue plays a dual role of promoting T2D and providing a relatively safe place to store POPs. Large prospective studies with serial measurements of a broad range of POPs, adiposity, and clinically relevant biomarkers are needed to disentangle the interrelationships among POPs, obesity, and the development of T2D. Also needed are laboratory experiments that more closely mimic real-world POP doses, mixtures, and exposure duration in humans. PMID:24483949

  2. [Studies of lipoprotein lipase activity and adipocyte characteristics in the human: effect of obesity and diabetes (author's transl)].

    PubMed

    Jaillard, J; Sezille, G; Fruchart, J C; Dewailly, P; Romon, M

    1976-03-01

    Adipose tissue lipoprotein lipase activity (LPLA) and cellularity have been studied in controls, in diabetic or non-diabetic obese subjects and in insulin dependent diabetic patients. LPLA is increased in diabetic or non-diabetic obese subjects and in insulin dependent diabetic patients. LPLA is increased in diabetic or non-diabetic obese subjects (p less than 0.02) and decreased in insulin dependent diabetic patients (p less than 0.02). Adipocyte size is larger in obese subjects, whether diabetic or not (p less than 0.05). As defined by LPLA and cell size means, the different groups are related linearly. The implications of this relationship between LPLA and adipocyte size are considered.

  3. Exotic Fruits as Therapeutic Complements for Diabetes, Obesity and Metabolic Syndrome

    PubMed Central

    Devalaraja, Samir; Jain, Shalini; Yadav, Hariom

    2011-01-01

    The prevalence and severity of obesity, type 2-diabetes, and the resultant metabolic syndrome are rapidly increasing. As successful preventive and therapeutic strategies for these life-threatening health ailments often come with adverse side effects, nutritional elements are widely used in many countries as preventive therapies to prevent or manage metabolic syndrome. Fruits are important dietary components, and contain various bioactive constituents. Many of these constituents have been proven to be useful to manage and treat various chronic diseases such as diabetes, obesity, cancer and cardiovascular diseases. Although exotic fruits are understudied throughout the world due to their limited regional presence, many studies reveal their potent ability to ameliorate metabolic derangements and the resultant conditions i.e. diabetes and obesity. The aim of this article is to review the role of exotic fruits and their constituents in the regulation of metabolic functions, which can beneficially alter diabetes and obesity pathophysiology. PMID:21857774

  4. Restrictive pulmonary deficit is associated with inflammation in sub-optimally controlled obese diabetics

    PubMed Central

    Seemungal, Terence A. R.; Teelucksingh, Surujpal; Nayak, B. Shivananda

    2013-01-01

    Caribbean data linking inflammation, pulmonary dysfunction and diabetes is unavailable. Spirometry, acanthosis nigricans, hs-CRP were assessed in 109 type 2 diabetics (43% males) mean age=55.6 years, BMI=29.29 kg/m2, waist circumference=103.86 cm. Residual FEV1/FVC increased with age (P=0.005), BMI (P=0.011) and waist circumference (P=0.003). Residual FVC related inversely to hs-CRP (–0.178), P<0.06) systolic (–0.028, P<0.031), diastolic (–0.247, P<0.010) pressure and weight (–0.25, P<0.009). Residual FEV1 related inversely to diastolic pressure (–0.219, P<0.023), hs-CRP (–0.234, P<0.015), acanthosis nigricans (–0.029, P<0.029). HbA1C and residual FEV1 predict high hs-CRP (P=0.011, P=0.046). Low FVC with inflammation presents in poorly controlled obese diabetics. PMID:23825761

  5. Expression of fourteen novel obesity-related genes in zucker diabetic fatty rats

    PubMed Central

    2012-01-01

    Background Genome-wide association studies (GWAS) are useful to reveal an association between single nucleotide polymorphisms and different measures of obesity. A multitude of new loci has recently been reported, but the exact function of most of the according genes is not known. The aim of our study was to start elucidating the function of some of these genes. Methods We performed an expression analysis of fourteen genes, namely BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MCR4, MTCH2, NEGR1, NRXN3, TMEM18, SEC16B and TFAP2B, via real-time RT-PCR in adipose tissue of the kidney capsule, the mesenterium and subcutaneum as well as the hypothalamus of obese Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats at an age of 22 weeks. Results All of our target genes except for SEC16B showed the highest expression in the hypothalamus. This suggests a critical role of these obesity-related genes in the central regulation of energy balance. Interestingly, the expression pattern in the hypothalamus showed no differences between obese ZDF and lean ZL rats. However, LYPLAL1, TFAP2B, SEC16B and FAIM2 were significantly lower expressed in the kidney fat of ZDF than ZL rats. NEGR1 was even lower expressed in subcutaneous and mesenterial fat, while MTCH2 was higher expressed in the subcutaneous and mesenterial fat of ZDF rats. Conclusion The expression pattern of the investigated obesity genes implies for most of them a role in the central regulation of energy balance, but for some also a role in the adipose tissue itself. For the development of the ZDF phenotype peripheral rather than central mechanisms of the investigated genes seem to be relevant. PMID:22553958

  6. Epigenetic programming of obesity and diabetes by in utero exposure to gestational diabetes mellitus.

    PubMed

    Ruchat, Stephanie-May; Hivert, Marie-France; Bouchard, Luigi

    2013-10-01

    It is now well accepted that offspring exposed to maternal undernutrition, obesity, or gestational diabetes mellitus have an increased risk for chronic diseases later in life, supporting the theory of the early origins of chronic diseases. However, the molecular mechanisms through which the exposure to an altered in utero environment translates into the development of chronic diseases are not yet well understood. Recently reported promising results help to resolve this issue. They suggest that epigenetic modifications are a potential mechanism for fetal metabolic programming. This review provides an overview of the relationship between the exposure to an altered intrauterine environment and fetal metabolic programming, focusing on gestational diabetes mellitus and epigenetic variations at adipokine candidate genes.

  7. From obesity to diabetes and cancer: epidemiological links and role of therapies

    PubMed Central

    García-Jiménez, Custodia; Gutiérrez-Salmerón, María; Chocarro-Calvo, Ana; García-Martinez, Jose Manuel; Castaño, Angel; De la Vieja, Antonio

    2016-01-01

    Increasing evidence suggests a complex relationship between obesity, diabetes and cancer. Here we review the evidence for the association between obesity and diabetes and a wide range of cancer types. In many cases the evidence for a positive association is strong, but for other cancer types a more complex picture emerges with some site-specific cancers associated with obesity but not to diabetes, and some associated with type I but not type II diabetes. The evidence therefore suggests the existence of cumulative common and differential mechanisms influencing the relationship between these diseases. Importantly, we highlight the influence of antidiabetics on cancer and antineoplastic agents on diabetes and in particular that antineoplastic targeting of insulin/IGF-1 signalling induces hyperglycaemia that often evolves to overt diabetes. Overall, a coincidence of diabetes and cancer worsens outcome and increases mortality. Future epidemiology should consider dose and time of exposure to both disease and treatment, and should classify cancers by their molecular signatures. Well-controlled studies on the development of diabetes upon cancer treatment are necessary and should identify the underlying mechanisms responsible for these reciprocal interactions. Given the global epidemic of diabetes, preventing both cancer occurrence in diabetics and the onset of diabetes in cancer patients will translate into a substantial socioeconomic benefit. PMID:26908326

  8. From obesity to diabetes and cancer: epidemiological links and role of therapies.

    PubMed

    García-Jiménez, Custodia; Gutiérrez-Salmerón, María; Chocarro-Calvo, Ana; García-Martinez, Jose Manuel; Castaño, Angel; De la Vieja, Antonio

    2016-03-29

    Increasing evidence suggests a complex relationship between obesity, diabetes and cancer. Here we review the evidence for the association between obesity and diabetes and a wide range of cancer types. In many cases the evidence for a positive association is strong, but for other cancer types a more complex picture emerges with some site-specific cancers associated with obesity but not to diabetes, and some associated with type I but not type II diabetes. The evidence therefore suggests the existence of cumulative common and differential mechanisms influencing the relationship between these diseases. Importantly, we highlight the influence of antidiabetics on cancer and antineoplastic agents on diabetes and in particular that antineoplastic targeting of insulin/IGF-1 signalling induces hyperglycaemia that often evolves to overt diabetes. Overall, a coincidence of diabetes and cancer worsens outcome and increases mortality. Future epidemiology should consider dose and time of exposure to both disease and treatment, and should classify cancers by their molecular signatures. Well-controlled studies on the development of diabetes upon cancer treatment are necessary and should identify the underlying mechanisms responsible for these reciprocal interactions. Given the global epidemic of diabetes, preventing both cancer occurrence in diabetics and the onset of diabetes in cancer patients will translate into a substantial socioeconomic benefit. PMID:26908326

  9. Metformin Suppresses Diethylnitrosamine-Induced Liver Tumorigenesis in Obese and Diabetic C57BL/KsJ-+Leprdb/+Leprdb Mice

    PubMed Central

    Shirakami, Yohei; Baba, Atsushi; Kochi, Takahiro; Kubota, Masaya; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

    2015-01-01

    Obesity and related metabolic disorders, such as diabetes mellitus, raise the risk of liver carcinogenesis. Metformin, which is widely used in the treatment of diabetes, ameliorates insulin sensitivity. Metformin is also thought to have antineoplastic activities and to reduce cancer risk. The present study examined the preventive effect of metformin on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-+Leprdb/+Leprdb (db/db) obese and diabetic mice. The mice were given a single injection of DEN at 2 weeks of age and subsequently received drinking water containing metformin for 20 weeks. Metformin administration significantly reduced the multiplicity of hepatic premalignant lesions and inhibited liver cell neoplasms. Metformin also markedly decreased serum levels of insulin and reduced insulin resistance, and inhibited phosphorylation of Akt, mammalian target of rapamycin (mTOR), and p70S6 in the liver. Furthermore, serum levels of leptin were decreased, while those of adiponectin were increased by metformin. These findings suggest that metformin prevents liver tumorigenesis by ameliorating insulin sensitivity, inhibiting the activation of Akt/mTOR/p70S6 signaling, and improving adipokine imbalance. Therefore, metformin may be a potent candidate for chemoprevention of liver tumorigenesis in patients with obesity or diabetes. PMID:25879666

  10. The relationship between serum 25-hydroxy vitamin D concentration and obesity in type 2 diabetic patients and healthy subjects

    PubMed Central

    2012-01-01

    Background Both obesity and type 2 diabetes are associated with hypovitaminosis D. The aims of this study were to investigate the association of serum 25-hydroxy vitamin D (25(OH) D) and parathyroid hormone (PTH) concentration with body mass index (BMI) in type 2 diabetic patients compared to control subjects and their predicting role in obesity. Methods This cross-sectional study was conducted on 200 subjects (100 type 2 diabetics and 100 healthy controls). Concentration of 25(OH) D, calcium, phosphorous, parathyroid hormone (PTH), fasting blood glucose, HbA1c, serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR) was determined in the fasting samples. Anthropometric measurements including body mass index (BMI) were also measured. Results Eighty-five percent of type 2 diabetics and 79% of healthy subjects were suffering from vitamin D deficiency or insufficiency. Serum concentration of 25(OH) D (22.08 ± 15.20 ng/ml) (r = −0.11, P = 0.04) and calcium (8.94 ± 0.59 mg/dl) (r = −2.25, P = 0.04) has significant statistically with BMI in type 2 diabetic patients. Serum concentration of PTH has non-significantly associated with BMI in diabetic patients and healthy subjects. Conclusion Serum levels of vitamin D inversely and PTH positively are associated with BMI after adjusted for age, gender and serum calcium in both type 2 diabetic patients and healthy subjects. These associations were statistically significant for serum concentration of vitamin D and calcium only in diabetic patients. So the status of vitamin D is considered as an important factor in type 2 diabetic patients. PMID:23497722

  11. Improvement in nutrition-related knowledge and behaviour of urban Asian Indian school children: findings from the 'Medical education for children/Adolescents for Realistic prevention of obesity and diabetes and for healthy aGeing' ( MARG) intervention study.

    PubMed

    Shah, Priyali; Misra, Anoop; Gupta, Nidhi; Hazra, Daya Kishore; Gupta, Rajeev; Seth, Payal; Agarwal, Anand; Gupta, Arun Kumar; Jain, Arvind; Kulshreshta, Atul; Hazra, Nandita; Khanna, Padmamalika; Gangwar, Prasann Kumar; Bansal, Sunil; Tallikoti, Pooja; Mohan, Indu; Bhargava, Rooma; Sharma, Rekha; Gulati, Seema; Bharadwaj, Swati; Pandey, Ravindra Mohan; Goel, Kashish

    2010-08-01

    Increasing prevalence of childhood obesity calls for comprehensive and cost-effective educative measures in developing countries such as India. School-based educative programmes greatly influence children's behaviour towards healthy living. We aimed to evaluate the impact of a school-based health and nutritional education programme on knowledge and behaviour of urban Asian Indian school children. Benchmark assessment of parents and teachers was also done. We educated 40 196 children (aged 8-18 years), 25 000 parents and 1500 teachers about health, nutrition, physical activity, non-communicable diseases and healthy cooking practices in three cities of North India. A pre-tested questionnaire was used to assess randomly selected 3128 children, 2241 parents and 841 teachers before intervention and 2329 children after intervention. Low baseline knowledge and behaviour scores were reported in 75-94 % government and 48-78 % private school children, across all age groups. A small proportion of government school children gave correct answers about protein (14-17 %), carbohydrates (25-27 %) and saturated fats (18-32 %). Private school children, parents and teachers performed significantly better than government school subjects (P < 0.05). Following the intervention, scores improved in all children irrespective of the type of school (P < 0.001). A significantly higher improvement was observed in younger children (aged 8-11 years) as compared with those aged 12-18 years, in females compared with males and in government schools compared with private schools (P < 0.05 for all). Major gaps exist in health and nutrition-related knowledge and behaviour of urban Asian Indian children, parents and teachers. This successful and comprehensive educative intervention could be incorporated in future school-based health and nutritional education programmes.

  12. A Metabolomic Approach to Understanding the Metabolic Link between Obesity and Diabetes

    PubMed Central

    Park, Seokjae; Sadanala, Krishna Chaitanya; Kim, Eun-Kyoung

    2015-01-01

    Obesity and diabetes arise from an intricate interplay between both genetic and environmental factors. It is well recognized that obesity plays an important role in the development of insulin resistance and diabetes. Yet, the exact mechanism of the connection between obesity and diabetes is still not completely understood. Metabolomics is an analytical approach that aims to detect and quantify small metabolites. Recently, there has been an increased interest in the application of metabolomics to the identification of disease biomarkers, with a number of well-known biomarkers identified. Metabolomics is a potent approach to unravel the intricate relationships between metabolism, obesity and progression to diabetes and, at the same time, has potential as a clinical tool for risk evaluation and monitoring of disease. Moreover, metabolomics applications have revealed alterations in the levels of metabolites related to obesity-associated diabetes. This review focuses on the part that metabolomics has played in elucidating the roles of metabolites in the regulation of systemic metabolism relevant to obesity and diabetes. It also explains the possible metabolic relation and association between the two diseases. The metabolites with altered profiles in individual disorders and those that are specifically and similarly altered in both disorders are classified, categorized and summarized. PMID:26072981

  13. Common Variations in Perilipin Gene, Central Obesity, and Risk of Type 2 diabetes in US Women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: The variations in perilipin gene (PLIN) were previously associated with obesity and insulin sensitivity. We examined whether PLIN variability was associated with diabetes risk and whether obesity status modified such associations. Research Methods and Procedures: We conducted a nested cas...

  14. A CLINICAL EVALUATION OF SKIN TAGS IN RELATION TO OBESITY, TYPE 2 DIABETIS MELLITUS, AGE, AND SEX

    PubMed Central

    El Safoury, Omar Soliman; Ibrahim, Magdy

    2011-01-01

    Background: Skin tags (STs) have been investigated as a marker of type 2 diabetes mellitus (DM), yet the relation of STs to obesity is still a matter of controversy. Aim: The aim of the study is to explore the relation of number, size and color of STs to obesity, diabetes, sex and age in one study. Methods: The study included 245 nondiabetic (123 males and 122 females) and 276 diabetic (122 males and 154 females) subjects. We recorded age, sex, body mass index (BMI), relevant habits, STs color, size, and number in different anatomical sites. Results: The presence and the mean number of STs was more in obese than nonobese participants (P = 0.006 and P < 0.001, respectively) and was not affected by sex. However, the number increased significantly with age. The presence of mixed-color STs was related to obese (P < 0.001) participants. Multivariate logistic regression revealed that only BMI was significantly associated with the mixed-color STs (OR = 3.5, P < 0.001). The association of DM (OR = 1.7) with mixed-color STs was nonsignificant (P = 0.073). Neither age nor sex had any association with mixed-color STs. Within cases that developed mixed-color STs, the multivariate analysis showed that only BMI had a significant correlation to the number of STs (beta = 0.256, P = 0.034). Conclusion: The study showed that not only the number but also the presence of mixed-color ST was related to obesity, but not to diabetes. The presence of mixed-color STs in nondiabetic subjects needs close inspection of BMI. PMID:21965846

  15. Epidemiology of diabetes mellitus in old age in Japan.

    PubMed

    Nakano, Tadasumi; Ito, Hideki

    2007-09-01

    Epidemiological studies on diabetes mellitus revealed that the number of patients with diabetes mellitus is gradually increasing in Japan along with development of car society and westernization of food intake. Since prevalence of diabetes mellitus increases with aging, proportion of individuals with diabetes mellitus aged over 60 has exceeded two-third of estimated total number of patients (7.40 million in 2002) in Japan where aging of society is rapidly progressing. Type 2 diabetes mellitus is common in diabetes mellitus in old age, and there are rarely elderly patients with type 1 diabetes mellitus. Prevalence of both diabetic microangiopathy and atherosclerotic vascular diseases is higher in the elderly with diabetes mellitus than in the middle-aged with diabetes mellitus. Furthermore, atherosclerotic vascular diseases (ischemic heart disease, cerebro-vascular disease and peripheral vascular disease) are more prevalent in the elderly with diabetes mellitus than in those without diabetes mellitus. Many studies demonstrated that functional declines, i.e. decreases in activities of daily living, physical activity and cognitive function, deteriorated quality of life in the elderly, and functional declines are more prominent in the elderly with diabetes mellitus than in those without diabetes mellitus. In order to clarify how the elderly patients with diabetes mellitus should be treated to maintain their quality of life, a nationwide randomized controlled intervention study using 1173 Japanese elderly patients with diabetes mellitus is now performing. In summary, number of elderly patients with diabetes mellitus is overwhelmingly increasing in Japan as well as in westernized countries. It is necessary for us to treat the elderly with diabetes mellitus to maintain their function and quality of life. PMID:17644210

  16. Dyslipidemia in Overweight and Obese School-Aged Children.

    PubMed

    Finn, Pamela

    2015-09-01

    Dyslipidemia often affects overweight and obese adolescents and can be present along with hypertension, insulin resistance, type 2 diabetes, and polycystic ovarian syndrome. This article is the third of six discussing the comorbidities of childhood obesity and will focus on the individual parts of the lipid profile and the impact of dyslipidemia on the heart and other body systems. Since few pharmacologic therapies are approved to treat dyslipidemia in children and adolescents younger than 18, treatment consists of lifestyle changes that can be supported and modeled by the school nurse. The school nurse can also be an advocate for a healthy lifestyle in the school district and community. More success in the treatment of dyslipidemia will be realized with less attention to changing the individual and more attention to changing the wider populations, including schools and the community. PMID:26219905

  17. Prevention of type 2 diabetes in obese at-risk subjects: a systematic review and meta-analysis.

    PubMed

    Merlotti, Claudia; Morabito, Alberto; Ceriani, Valerio; Pontiroli, Antonio E

    2014-10-01

    Different intervention strategies can prevent new cases of type 2 diabetes (T2DM) in obese subjects. The present systematic review and meta-analysis evaluates the effectiveness of different strategies in prevention of type 2 diabetes in obese subjects. Studies were grouped into five different strategies: (1) physical activity ± diet; (2) anti-diabetic drugs (glitazones, metformin, glinides, alfa-glucosidase inhibitors); (3) antihypertensive drugs (ACE inhibitors, ARB); (4) weight loss-promoting drugs and lipid-lowering drugs (orlistat, bezafibrate, phentermine/topiramate controlled release); and (5) bariatric surgery. Only controlled studies, dealing with subjects BMI ≥ 30 kg/m(2), were included in the analysis, whether randomized or non-randomized studies. Appropriate methodology (PRISMA statement) was adhered to. Publication bias was formally assessed. Eighteen studies (43,669 subjects, 30,774 with impaired glucose tolerance and/or impaired fasting glucose), published in English language as full papers, were analyzed to identify predictors of new cases of T2DM and were included in a meta-analysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95 % confidence intervals (CIs). In obese subjects, non-surgical strategies were able to prevent T2DM, with different effectiveness [OR from 0.44 (0.36-0.52) to 0.86 (0.80-0.92)]; in morbidly obese subjects, bariatric surgery was highly effective [OR = 0.10 (0.02-0.49)]. At meta-regression analysis, factors associated with effectiveness were weight loss, young age and fasting insulin levels. Publication bias was present only when considering all studies together. These data indicate that several strategies, with different effectiveness, can prevent T2DM in obese subjects. PMID:25085464

  18. Sleep disorders, obesity, and aging: the role of orexin.

    PubMed

    Nixon, Joshua P; Mavanji, Vijayakumar; Butterick, Tammy A; Billington, Charles J; Kotz, Catherine M; Teske, Jennifer A

    2015-03-01

    The hypothalamic neuropeptides orexin A and B (hypocretin 1 and 2) are important homeostatic mediators of central control of energy metabolism and maintenance of sleep/wake states. Dysregulation or loss of orexin signaling has been linked to narcolepsy, obesity, and age-related disorders. In this review, we present an overview of our current understanding of orexin function, focusing on sleep disorders, energy balance, and aging, in both rodents and humans. We first discuss animal models used in studies of obesity and sleep, including loss of function using transgenic or viral-mediated approaches, gain of function models using exogenous delivery of orexin receptor agonist, and naturally-occurring models in which orexin responsiveness varies by individual. We next explore rodent models of orexin in aging, presenting evidence that orexin loss contributes to age-related changes in sleep and energy balance. In the next section, we focus on clinical importance of orexin in human obesity, sleep, and aging. We include discussion of orexin loss in narcolepsy and potential importance of orexin in insomnia, correlations between animal and human studies of age-related decline, and evidence for orexin involvement in age-related changes in cognitive performance. Finally, we present a summary of recent studies of orexin in neurodegenerative disease. We conclude that orexin acts as an integrative homeostatic signal influencing numerous brain regions, and that this pivotal role results in potential dysregulation of multiple physiological processes when orexin signaling is disrupted or lost.

  19. Sleep disorders, obesity, and aging: the role of orexin

    PubMed Central

    Nixon, Joshua P.; Mavanji, Vijayakumar; Butterick, Tammy A.; Billington, Charles J.; Kotz, Catherine M.; Teske, Jennifer A.

    2015-01-01

    The hypothalamic neuropeptides orexin A and B (hypocretin 1 and 2) are important homeostatic mediators of central control of energy metabolism and maintenance of sleep/wake states. Dysregulation or loss of orexin signaling has been linked to narcolepsy, obesity, and age-related disorders. In this review, we present an overview of our current understanding of orexin function, focusing on sleep disorders, energy balance, and aging, in both rodents and humans. We first discuss animal models used in studies of obesity and sleep, including loss of function using transgenic or viral-mediated approaches, gain of function models using exogenous delivery of orexin receptor agonist, and naturally-occurring models in which orexin responsiveness varies by individual. We next explore rodent models of orexin in aging, presenting evidence that orexin loss contributes to age-related changes in sleep and energy balance. In the next section, we focus on clinical importance of orexin in human obesity, sleep, and aging. We include discussion of orexin loss in narcolepsy and potential importance of orexin in insomnia, correlations between animal and human studies of age-related decline, and evidence for orexin involvement in age-related changes in cognitive performance. Finally, we present a summary of recent studies of orexin in neurodegenerative disease. We conclude that orexin acts as an integrative homeostatic signal influencing numerous brain regions, and that this pivotal role results in potential dysregulation of multiple physiological processes when orexin signaling is disrupted or lost. PMID:25462194

  20. Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production

    PubMed Central

    Ip, Blanche; Cilfone, Nicholas; Belkina, Anna C.; DeFuria, Jason; Jagannathan-Bogdan, Madhumita; Zhu, Min; Kuchibhatla, Ramya; McDonnell, Marie E.; Xiao, Qiang; Kepler, Thomas B.; Apovian, Caroline M.; Lauffenburger, Douglas A.; Nikolajczyk, Barbara S.

    2015-01-01

    Objective T cell inflammation plays pivotal roles in obesity-associated type 2 diabetes (T2DM). The identification of dominant sources of T cell inflammation in humans remains a significant gap in understanding disease pathogenesis. We hypothesized that cytokine profiles from circulating T cells identify T cell subsets and T cell cytokines that define T2DM-associated inflammation. Methods We used multiplex analyses to quantify T cell-associated cytokines in αCD3/αCD28-stimulated PBMCs, or B cell-depleted PBMCs, from subjects with T2DM or BMI-matched controls. We subjected cytokine measurements to multivariate (principal component and partial least squares) analyses. Flow cytometry detected intracellular TNFα in multiple immune cells subsets in the presence/absence of antibodies that neutralize T cell cytokines. Results T cell cytokines were generally higher in T2DM samples, but Th17 cytokines are specifically important for classifying individuals correctly as T2DM. Multivariate analyses indicated that B cells support Th17 inflammation in T2DM but not control samples, while monocytes supported Th17 inflammation regardless of T2DM status. Partial least squares regression analysis indicated that both Th17 and Th1 cytokines impact %HbA1c. Conclusions Among various T cell subsets, Th17 cells are major contributors to inflammation and hyperglycemia, and are uniquely supported by B cells in obesity-associated T2DM. PMID:26576827

  1. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy.

    PubMed

    Schmidt, Robert E; Dorsey, Denise A; Beaudet, Lucie N; Frederick, Kathy E; Parvin, Curtis A; Plurad, Santiago B; Levisetti, Matteo G

    2003-11-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man. PMID:14578206

  2. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy.

    PubMed

    Schmidt, Robert E; Dorsey, Denise A; Beaudet, Lucie N; Frederick, Kathy E; Parvin, Curtis A; Plurad, Santiago B; Levisetti, Matteo G

    2003-11-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man.

  3. Immunization of AGE-modified albumin inhibits diabetic nephropathy progression in diabetic mice

    PubMed Central

    Mashitah, Musthika Wida; Azizah, Nurona; Samsu, Nur; Indra, Muhammad Rasjad; Bilal, Muhammad; Yunisa, Meti Verdian; Arisanti, Amildya Dwi

    2015-01-01

    Background Diabetic nephropathy (DN) is a serious vascular complication of diabetes and an important cause of end-stage renal disease. One mechanism by which hyperglycemia causes nephropathy is through the formation of advanced glycation end products (AGE). Development of vaccination would be a promising therapy for the future, while to date, anti-AGE therapy is based on medicines that are needed to be consumed lifelong. This study aimed to find out the effect of immunization of AGE-modified albumin against DN pathogenesis in streptozotocin-induced diabetic in mice. Methods We used 24 BALB/c male mice as experimental animals, which were divided into six groups, two nondiabetic groups (negative control and AGE-modified bovine serum albumin [BSA] preimmunized groups) and four streptozotocin-induced diabetic groups (diabetic control group and diabetic preimmunized groups for AGE-BSA, Keyhole limpet hemocyanin (KLH), and AGE-BSA-KLH, respectively). Results Diabetic preimmunized groups for AGE-BSA, KLH, and AGE-BSA-KLH showed amelioration in renal function and histopathology compared with the diabetic control group. Preimmunization also maintained nephrin intensity and decreased serum AGE level, kidney AGE deposition, and kidney cells apoptosis. Conclusion AGE-BSA and AGE-BSA-KLH immunizations inhibit the progression of DN. Our results strengthen the evidence that the anti-AGE antibodies have a protective role against diabetic vascular complication, especially DN. This study provides a basis for the development of DN-based immunotherapy with AGE immunization as a potential candidate. PMID:26346342

  4. Diabetes mellitus and its association with central obesity and disability among older adults: a global perspective.

    PubMed

    Tyrovolas, Stefanos; Koyanagi, Ai; Garin, Noe; Olaya, Beatriz; Ayuso-Mateos, Jose Luis; Miret, Marta; Chatterji, Somnath; Tobiasz-Adamczyk, Beata; Koskinen, Seppo; Leonardi, Matilde; Haro, Josep Maria

    2015-04-01

    The aim of the study was to evaluate the association between various factors and diabetes type II (DM) with a particular emphasis on indicators of central obesity, and to compare the effect of DM on disability among elder populations (≥ 50 years old) in nine countries. Data were available for 52,946 people aged ≥ 18 years who participated in the WHO Study on global AGEing and adult health and the Collaborative Research on Ageing in Europe studies conducted between 2007 and 2012. DM was defined as self-report of physician diagnosis. Height, weight, and waist circumference were measured. Disability status was assessed with the WHODAS II questionnaire. The overall prevalence of DM was 7.9% and ranged from 3.8% (Ghana) to 17.6% (Mexico). A 10 cm increase in waist circumference and waist-to-height ratio of >0.5 were associated with a significant 1.26 (India) to 1.77 (Finland), and 1.68 (China, Spain) to 5.40 (Finland) times higher odds for DM respectively. No significant associations were observed in Mexico and South Africa. DM was associated with significantly higher disability status in all countries except Mexico in the model adjusted for demographics and smoking. The inclusion of chronic conditions associated with diabetes in the model attenuated the coefficients in varying degrees depending on the country. A considerable proportion of the studied older population had DM. Central obesity may be a key factor for the prevention of DM among older populations globally. Prevention of DM especially among the older population globally may contribute to reducing the burden of disability.

  5. A susceptibility gene for kidney disease in an obese mouse model of type II diabetes maps to chromosome 8

    PubMed Central

    Chua, Streamson; Li, Yifu; Liu, Shun Mei; Liu, Ruijie; Chan, Ka Tak; Martino, Jeremiah; Zheng, Zongyu; Susztak, Katalin; D'Agati, Vivette D; Gharavi, Ali G.

    2014-01-01

    Most mouse models of diabetes do not fully reproduce features of human diabetic nephropathy, limiting their utility in inferring mechanisms of human disease. Here we performed detailed phenotypic and genetic characterization of leptin-receptor (Lepr) deficient mice on the FVB/NJ background (FVBdb/db), an obese model of type II diabetes, to determine their suitability to model human diabetic nephropathy. These mice have sustained hyperglycemia, significant albuminuria and characteristic diabetic renal findings including mesangial sclerosis and nodular glomerulosclerosis after 6 months of age. In contrast, equally obese, hyperglycemic Lepr/Sur1 deficient C57BL/6J (Sur1 has defective insulin secretion) mice have minimal evidence of nephropathy. A genome-wide scan in 165 Lepr deficient backcross progeny derived from FVB/NJ and C57BL/6J identified a major locus influencing nephropathy and albuminuria on chromosome 8B1-C5 (Dbnph1 locus, peak lod score 5.0). This locus was distinct from those contrasting susceptibility to beta cell hypertrophy and HIV-nephropathy between the same parental strains, indicating specificity to diabetic kidney disease. Genome-wide expression profiling showed that high and low risk Dbnph1 genotypes were associated with significant enrichment for oxidative phosphorylation and lipid clearance, respectively; molecular pathways shared with human diabetic nephropathy. Hence, we found that the FVBdb/db mouse recapitulates many clinical, histopathological and molecular features of human diabetic nephropathy. Identifying underlying susceptibility gene(s) and downstream dysregulated pathways in these mice may provide insight into the disease pathogenesis in humans. PMID:20520596

  6. Synchronized human skeletal myotubes of lean, obese and type 2 diabetic patients maintain circadian oscillation of clock genes

    PubMed Central

    Hansen, Jan; Timmers, Silvie; Moonen-Kornips, Esther; Duez, Helene; Staels, Bart; Hesselink, Matthijs K. C.; Schrauwen, Patrick

    2016-01-01

    Cell and animal studies have demonstrated that circadian rhythm is governed by autonomous rhythmicity of clock genes. Although disturbances in circadian rhythm have been implicated in metabolic disease development, it remains unknown whether muscle circadian rhythm is altered in human models of type 2 diabetes. Here we used human primary myotubes (HPM) to investigate if rhythmicity of clock- and metabolic gene expression is altered in donors with obesity or type 2 diabetes compared to metabolically healthy donors. HPM were obtained from skeletal muscle biopsies of four groups: type 2 diabetic patients and their BMI- and age-matched obese controls and from lean, healthy and young endurance trained athletes and their age-matched sedentary controls. HPM were differentiated for 7 days before synchronization by serum shock followed by gene expression profiling over the next 72 hours. HPM display robust circadian rhythms in clock genes, but REVERBA displayed dampened rhythmicity in type 2 diabetes. Furthermore, rhythmicity in NAMPT and SIRT1 expression was only observed in HPM from trained athletes. Rhythmicity in expression of key-regulators of carbohydrate and lipid metabolism was modest. We demonstrate that in human skeletal muscle REVERBA/B, NAMPT and SIRT1 circadian rhythms are affected in donors of sedentary life style and poor health status. PMID:27756900

  7. [Gene-nutrient interaction and its association with obesity and diabetes mellitus].

    PubMed

    Steemburgo, Thais; Azevedo, Mirela J de; Martínez, José Alfredo

    2009-07-01

    Nutritional genomics evaluates the effects of genetic variation in the interaction between diet and chronic diseases. The aim of this manuscript was to review the most important genetic polymorphisms associated with obesity, diabetes mellitus, and dietary factors. The main interactions among genetic polymorphisms and diet were: for obesity: interleukin-6 (IL-6) with daily intake; peroxisome proliferator-activated receptor gamma 2 (PPAR-gama2) and fat mass and obesity associated (FTO) with fat intake; beta-adrenergic receptor 2 (ADRB2) and melanocortin receptor 4 (MCR4) with carbohydrate intake; or reduction in body weight: uncoupling proteins (UCPs) with restriction of energy; for leptinemia: leptin receptor (LEPR) with restriction of energy; for diabetes mellitus: PPAR-gama2 with fat intake; for hypertriglyceridemia: fatty acid-binding protein 2 (FABP2) with fat intake. The data demonstrated suggest that nutritional genomics is important for the development of obesity and diabetes mellitus.

  8. Effect of Maternal Age at Childbirth on Obesity in Postmenopausal Women

    PubMed Central

    We, Ji-Sun; Han, Kyungdo; Kwon, Hyuk-Sang; Kil, Kicheol

    2016-01-01

    Abstract The object of this study was to assess the obesity in postmenopausal women, according to age at childbirth. We analyzed the association between age at first childbirth, age at last childbirth, parity, and subject obesity status (general obesity; BMI >25 kg/m2, nongeneral obesity; BMI ≤25 kg/m2, abdominal obesity; waist circumference >85 cm, nonabdominal obesity; waist circumference ≤85 cm), using data from a nationwide population-based survey, the 2010 to 2012 Korean National Health and Nutrition Examination Survey. Data from a total of 4382 postmenopausal women were analyzed using multivariate regression analysis with complex survey design sampling. And, the subjects were subdivided into groups according to obesity or not. Age, smoking, alcohol consumption, exercise, education, income level, number of pregnancies, oral contraceptive uses, breast feeding experience were adjusted as the confounders. The prevalence of general obesity among Korean postmenopausal women was 37.08%. Women with general obesity and abdominal obesity were significantly younger at first childbirth compared with women with nongeneral obesity and no abdominal obesity (23.89 ± 0.1 vs. 23.22 ± 0.1, P <0.001). Age at first childbirth was inversely associated with obesity, while age at last childbirth was not associated with obesity or abdominal obesity. Women with a higher number of pregnancies were also more likely to have obesity and abdominal obesity. Age at first childbirth remained significantly associated with obesity, after adjusting for confounding factors. Obesity in postmenopausal women is associated with first childbirth at a young age, and higher parity. Further research is needed to clarify the association between obesity and reproductive characteristics. PMID:27175656

  9. Impact of obesity on hospital complications and mortality in hospitalized patients with hyperglycemia and diabetes

    PubMed Central

    Alexopoulos, Anastasia-Stefania; Fayfman, Maya; Zhao, Liping; Weaver, Jeff; Buehler, Lauren; Smiley, Dawn; Pasquel, Francisco J; Vellanki, Priyathama; Haw, J Sonya; Umpierrez, Guillermo E

    2016-01-01

    Objective Obesity is associated with increased risk of diabetes, hypertension and cardiovascular mortality. Several studies have reported increased length of hospital stay and complications; however, there are also reports of obesity having a protective effect on health, a phenomenon coined the ‘obesity paradox’. We aimed to investigate the impact of overweight and obesity on complications and mortality in hospitalized patients with hyperglycemia and diabetes. Research design and methods This retrospective analysis was conducted on 29 623 patients admitted to two academic hospitals in Atlanta, Georgia, between January 2012 and December 2013. Patients were subdivided by body mass index into underweight (body mass index <18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (>30 kg/m2). Hyperglycemia was defined as a blood glucose >10 mmol/L during hospitalization. Hospital complications included a composite of pneumonia, acute myocardial infarction, respiratory failure, acute kidney injury, bacteremia and death. Results A total of 4.2% were underweight, 29.6% had normal weight, 30.2% were overweight, and 36% were obese. 27.2% of patients had diabetes and 72.8% did not have diabetes (of which 75% had hyperglycemia and 25% had normoglycemia during hospitalization). A J-shaped curve with higher rates of complications was observed in underweight patients in all glycemic groups; however, there was no significant difference in the rate of complications among normal weight, overweight, or obese patients, with and without diabetes or hyperglycemia. Conclusions Underweight is an independent predictor for hospital complications. In contrast, increasing body mass index was not associated with higher morbidity or mortality, regardless of glycemic status. There was no evidence of an obesity paradox among inpatients with diabetes and hyperglycemia. PMID:27486518

  10. The Influence of Peripheral Neuropathy, Gender, and Obesity on the Postural Stability of Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Herrera-Rangel, Aline; Aranda-Moreno, Catalina; Mantilla-Ochoa, Teresa; Zainos-Saucedo, Lylia; Jáuregui-Renaud, Kathrine

    2014-01-01

    Aim. To assess the influence of peripheral neuropathy, gender, and obesity on the postural stability of patients with type 2 diabetes mellitus. Methods. 151 patients with no history of otology, neurology, or orthopaedic or balance disorders accepted to participate in the study. After a clinical interview and neuropathy assessment, postural stability was evaluated by static posturography (eyes open/closed on hard/soft surface) and the “Up & Go” test. Results. During static posturography, on hard surface, the length of sway was related to peripheral neuropathy, gender, age, and obesity; on soft surface, the length of sway was related to peripheral neuropathy, gender, and age, the influence of neuropathy was larger in males than in females, and closing the eyes increased further the difference between genders. The mean time to perform the “Up & Go” test was 11.6 ± 2.2 sec, with influence of peripheral neuropathy, gender, and age. Conclusion. In order to preserve the control of static upright posture during conditions with deficient sensory input, male patients with type 2 diabetes mellitus with no history of balance disorders may be more vulnerable than females, and obesity may decrease the static postural control in both males and females. PMID:25258716

  11. Work stress, obesity and the risk of type 2 diabetes: gender-specific bidirectional effect in the Whitehall II study.

    PubMed

    Heraclides, Alexandros M; Chandola, Tarani; Witte, Daniel R; Brunner, Eric J

    2012-02-01

    Psychosocial work stress has been linked to higher risk of type 2 diabetes (T2DM), with the effect being consistently higher among women than men. Also, work stress has been linked to prospective weight gain among obese men but weight loss among lean men. Here, we aimed to examine the interaction between work stress and obesity in relation to T2DM risk in a gender-specific manner. We studied 5,568 white middle-aged men and women in the Whitehall II study, who were free from diabetes at analysis baseline (1993). After 1993, diabetes was ascertained at six consecutive phases by an oral glucose tolerance test supplemented by self-reports. Cox regression analysis was used to assess the association between job strain (high job demands/low job control) and 18-year incident T2DM stratifying by BMI (BMI <30 kg/m(2) vs. BMI ≥30 kg/m(2)). Overall, work stress was associated with incident T2DM among women (hazard ratio (HR) 1.41: 95% confidence intervals: 1.02; 1.95) but not among men (HR 0.87: 95% confidence interval 0.69; 1.11) (P(INTERACTION) = 0.017). Among men, work stress was associated with a lower risk of T2DM in nonobese (HR 0.70: 0.53; 0.93) but not in obese individuals (P(INTERACTION) = 0.17). Among women, work stress was associated with higher risk of T2DM in the obese (HR 2.01: 1.06; 3.92) but not in the nonobese (P(INTERACTION) = 0.005). Gender and body weight status play a critical role in determining the direction of the association between psychosocial stress and T2DM. The potential effect-modifying role of gender and obesity should not be ignored by future studies looking at stress-disease associations.

  12. Diabetic nephropathy and long-term treatment effects of rosiglitazone and enalapril in obese ZSF1 rats.

    PubMed

    Bilan, Victor P; Salah, Eman M; Bastacky, Sheldon; Jones, Huw B; Mayers, Rachel M; Zinker, Bradley; Poucher, Simon M; Tofovic, Stevan P

    2011-09-01

    Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Yet the pathogenic mechanisms underlying the development of DN are not fully defined, partially due to lack of suitable models that mimic the complex pathogenesis of renal disease in diabetic patients. In this study, we describe early and late renal manifestations of DN and renal responses to long-term treatments with rosiglitazone or high-dose enalapril in ZSF1 rats, a model of metabolic syndrome, diabetes, and chronic renal disease. At 8 weeks of age, obese ZSF1 rats developed metabolic syndrome and diabetes (hyperglycemia, glucosuria, hyperlipidemia, and hypertension) and early signs of renal disease (proteinuria, glomerular collagen IV deposition, tubulointerstitial inflammation, and renal hypertrophy). By 32 weeks of age, animals developed renal histopathology consistent with DN, including mesangial expansion, glomerulosclerosis, tubulointerstitial inflammation and fibrosis, tubular dilation and atrophy, and arteriolar thickening. Rosiglitazone markedly increased body weight but reduced food intake, improved glucose control, and attenuated hyperlipidemia and liver and kidney injury. In contrast, rosiglitazone markedly increased cardiac hypertrophy via a blood pressure-independent mechanism. High-dose enalapril did not improve glucose homeostasis, but normalized blood pressure, and nearly prevented diabetic renal injury. The ZSF1 model thus detects the clinical observations seen with rosiglitazone and enalapril in terms of primary and secondary endpoints of cardiac and renal effects. This and previous reports indicate that the obese ZSF1 rat meets currently accepted criteria for progressive experimental diabetic renal disease in rodents, suggesting that this may be the best available rat model for simulation of human DN. PMID:21680617

  13. Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis

    PubMed Central

    Tellez-Avila, Felix I; Sanchez-Avila, Francisco; García-Saenz-de-Sicilia, Mauricio; Chavez-Tapia, Norberto C; Franco-Guzman, Ada M; Lopez-Arce, Gustavo; Cerda-Contreras, Eduardo; Uribe, Misael

    2008-01-01

    AIM: To evaluate the prevalence of metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) in a group of Mexican Mestizo patients with cryptogenic cirrhosis (CC) and to compare this group with patients with cirrhosis secondary to other causes (disease controls). METHODS: Patients with CC, diagnosed between January, 1990 and April, 2005, were included in a retrospective study. Patients with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune hepatitis (AIH) served as disease controls. RESULTS: A total of 134 patients with CC were analyzed. Disease controls consisted of 81 patients with chronic hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients with CC was 57 years (range, 16-87); 83 (61.9%) patients were female; 53 (39.6%) were Child A, 65 (48.5%) Child B, and 16 (11.9%) were Child C cirrhosis. The prevalence of MS (29.1% vs 6%; P < 0.001), obesity (16.4% vs 8.2%; P = 0.04) and T2DM (40% vs 22.4%; P = 0.013) was higher in CC patients than in disease controls. There were no differences in sex, age or liver function tests between the two groups. CONCLUSION: The prevalence of MS, obesity and T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes. Our findings support the hypothesis that non-alcoholic steatohepatitis (NASH) plays an under-recognized role in CC. PMID:18720537

  14. Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids

    PubMed Central

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Yin, Yingfu; Kim, Kyeongseok; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Obesity and diabetes are the most prevailing health concerns worldwide and their incidence is increasing at a high rate, resulting in enormous social costs. Obesity is a complex disease commonly accompanied by insulin resistance and increases in oxidative stress and inflammatory marker expression, leading to augmented fat mass in the body. Diabetes mellitus (DM) is a metabolic disorder characterized by the destruction of pancreatic β cells or diminished insulin secretion and action insulin. Obesity causes the development of metabolic disorders such as DM, hypertension, cardiovascular diseases, and inflammation-based pathologies. Flavonoids are the secondary metabolites of plants and have 15-carbon skeleton structures containing two phenyl rings and a heterocyclic ring. More than 5000 naturally occurring flavonoids have been reported from various plants and have been found to possess many beneficial effects with advantages over chemical treatments. A number of studies have demonstrated the potential health benefits of natural flavonoids in treating obesity and DM, and show increased bioavailability and action on multiple molecular targets. This review summarizes the current progress in our understanding of the anti-obesity and anti-diabetic potential of natural flavonoids and their molecular mechanisms for preventing and/or treating obesity and diabetes. PMID:27092490

  15. The incretin system ABCs in obesity and diabetes - novel therapeutic strategies for weight loss and beyond.

    PubMed

    João, A L; Reis, F; Fernandes, R

    2016-07-01

    Incretins are gastrointestinal-derived hormones released in response to a meal playing a key role in the regulation of postprandial secretion of insulin (incretin effect) and glucagon by the pancreas. Both incretins, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1), have several other actions by peripheral and central mechanisms. GLP-1 regulates body weight by inhibiting appetite and delaying gastric, emptying actions that are dependent on central nervous system GLP-1 receptor activation. Several other hormones and gut peptides, including leptin and ghrelin, interact with GLP-1 to modulate appetite. GLP-1 is rapidly degraded by the multifunctional enzyme dipeptidyl peptidase-4 (DPP-4). DPP-4 is involved in adipose tissue inflammation, which is associated with insulin resistance and diabetes progression, being a common pathophysiological mechanism in obesity-related complications. Furthermore, the incretin system appears to provide the basis for understanding the high weight loss efficacy of bariatric surgery, a widely used treatment for obesity, often in association with diabetes. The present review brings together new insights into obesity pathogenesis, integrating GLP-1 and DPP-4 in the complex interplay between obesity and inflammation, namely, in diabetic patients. This in turn will provide the basis for novel incretin-based therapeutic strategies for obesity and diabetes with promising benefits in addition to weight loss. © 2016 World Obesity.

  16. Exercise for prevention of obesity and diabetes in children and adolescents.

    PubMed

    McCall, Anthony; Raj, Ramona

    2009-07-01

    As rates of obesity and type 2 diabetes continue to escalate, effective means of prevention become paramount in curbing the largest epidemic of our times. With adult obesity rates in the United States already at 34%, according to the most recent National Health and Nutrition Examination Survey (NHANES) data, preventing obesity in childhood is of increasing urgency. Exercise and lifestyle modification have been shown to be effective in adult trials for diabetes prevention, such as the Diabetes Prevention Program (DPP), Finnish Diabetes Study, and Da Qing Study. This article reviews randomized, controlled trials in children, using exercise and lifestyle modification in the prevention of insulin resistance and obesity. This review encompasses studies within the past decade from Planet Health in 1999 to the Beijing Obesity Intervention trial published in 2007 and covers both school-based and family-based approaches. A challenging task by any means, these trials have contributed valuable insight into the efficacy of various approaches toward preventing childhood obesity and insulin resistance, a pressing public health concern.

  17. Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Yin, Yingfu; Kim, Kyeongseok; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Obesity and diabetes are the most prevailing health concerns worldwide and their incidence is increasing at a high rate, resulting in enormous social costs. Obesity is a complex disease commonly accompanied by insulin resistance and increases in oxidative stress and inflammatory marker expression, leading to augmented fat mass in the body. Diabetes mellitus (DM) is a metabolic disorder characterized by the destruction of pancreatic β cells or diminished insulin secretion and action insulin. Obesity causes the development of metabolic disorders such as DM, hypertension, cardiovascular diseases, and inflammation-based pathologies. Flavonoids are the secondary metabolites of plants and have 15-carbon skeleton structures containing two phenyl rings and a heterocyclic ring. More than 5000 naturally occurring flavonoids have been reported from various plants and have been found to possess many beneficial effects with advantages over chemical treatments. A number of studies have demonstrated the potential health benefits of natural flavonoids in treating obesity and DM, and show increased bioavailability and action on multiple molecular targets. This review summarizes the current progress in our understanding of the anti-obesity and anti-diabetic potential of natural flavonoids and their molecular mechanisms for preventing and/or treating obesity and diabetes. PMID:27092490

  18. The incretin system ABCs in obesity and diabetes - novel therapeutic strategies for weight loss and beyond.

    PubMed

    João, A L; Reis, F; Fernandes, R

    2016-07-01

    Incretins are gastrointestinal-derived hormones released in response to a meal playing a key role in the regulation of postprandial secretion of insulin (incretin effect) and glucagon by the pancreas. Both incretins, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1), have several other actions by peripheral and central mechanisms. GLP-1 regulates body weight by inhibiting appetite and delaying gastric, emptying actions that are dependent on central nervous system GLP-1 receptor activation. Several other hormones and gut peptides, including leptin and ghrelin, interact with GLP-1 to modulate appetite. GLP-1 is rapidly degraded by the multifunctional enzyme dipeptidyl peptidase-4 (DPP-4). DPP-4 is involved in adipose tissue inflammation, which is associated with insulin resistance and diabetes progression, being a common pathophysiological mechanism in obesity-related complications. Furthermore, the incretin system appears to provide the basis for understanding the high weight loss efficacy of bariatric surgery, a widely used treatment for obesity, often in association with diabetes. The present review brings together new insights into obesity pathogenesis, integrating GLP-1 and DPP-4 in the complex interplay between obesity and inflammation, namely, in diabetic patients. This in turn will provide the basis for novel incretin-based therapeutic strategies for obesity and diabetes with promising benefits in addition to weight loss. © 2016 World Obesity. PMID:27125902

  19. [Effects of diabetes and obesity on the higher brain functions in rodents].

    PubMed

    Asato, Megumi; Ikeda, Hiroko; Kamei, Junzo

    2012-11-01

    Metabolic disorders, such as diabetes and obesity, have been indicated to disturb the function of the central nervous system (CNS) as well as several peripheral organs. Clinically, it is well recognized that the prevalence of anxiety and depression is higher in diabetic and obesity patients than in the general population. We have recently indicated that streptozotocin-induced diabetic and diet-induced obesity mice have enhanced fear memory and higher anxiety-like behavior in several tests such as the conditioned fear, tail-suspension, hole-board and elevated open-platform tests. The changes in fear memory and anxiety-like behavior of diabetic and obese mice are due to the dysfunction of central glutamatergic and monoaminergic systems, which is mediated by the changes of intracellular signaling. These results suggest that metabolic disorders strongly affect the function of the CNS and disturb the higher brain functions. These dysfunctions of the CNS in diabetes and obesity are involved in the increased prevalence of anxiety disorders and depression. Normalization of these dysfunctions in the CNS will be a new attractive target to treat the metabolic disorders and their complications.

  20. Salacia root, a unique Ayurvedic medicine, meets multiple targets in diabetes and obesity.

    PubMed

    Li, Yuhao; Huang, Tom Hsun-Wei; Yamahara, Johji

    2008-05-23

    In many traditional schools of medicine it is claimed that a balanced modulation of several targets can provide a superior therapeutic effect and decrease in side effect profile compared to a single action from a single selective ligand, especially in the treatment of certain chronic and complex diseases, such as diabetes and obesity. Diabetes and obesity have a multi-factorial basis involving both genetic and environmental risk factors. A wide array of medicinal plants and their active constituents play a role in the prevention and treatment of diabetes. Salacia roots have been used in Ayurvedic medicine for diabetes and obesity since antiquity, and have been extensively consumed in Japan, the United States and other countries as a food supplement for the prevention of obesity and diabetes. Recent pharmacological studies have demonstrated that Salacia roots modulate multiple targets: peroxisome proliferator-activated receptor-alpha-mediated lipogenic gene transcription, angiotensin II/angiotensin II type 1 receptor, alpha-glucosidase, aldose reductase and pancreatic lipase. These multi-target actions may mainly contribute to Salacia root-induced improvement of type 2 diabetes and obesity-associated hyperglycemia, dyslipidemia and related cardiovascular complications seen in humans and rodents. The results of bioassay-guided identification indicate that mangiferin, salacinol, kotalanol and kotalagenin 16-acetate are at least in part responsible for these multi-target regulatory activities of Salacia roots. The evidence suggests that this unique traditional medicine fulfills a multiple-target strategy in the prevention and treatment of diabetes and obesity. Although toxicological studies have suggested minimal adverse effects of the herbal medicine in rodents, a clinical trial is crucial to further confirm the safety of Salacia roots. In addition, further mechanistic studies are necessary in order to allow a better understanding of how use of Salacia root may

  1. Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: A GWAS data analysis

    PubMed Central

    Tang, Hongwei; Wei, Peng; Duell, Eric J.; Risch, Harvey A.; Olson, Sara H.; Bueno-de-Mesquita, H. Bas; Gallinger, Steven; Holly, Elizabeth A.; Petersen, Gloria M.; Bracci, Paige M.; McWilliams, Robert R.; Jenab, Mazda; Riboli, Elio; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Kaaks, Rudolf; Trichopoulos, Dimitrios; Panico, Salvatore; Sund, Malin; Peeters, Petra H.M; Khaw, Kay-Tee; Amos, Christopher I; Li, Donghui

    2013-01-01

    Background Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level. Methods Using GWAS genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and gene-diabetes interactions in relation to pancreatic cancer risk by employing the likelihood ratio test (LRT) nested in logistic regression models and Ingenuity Pathway Analysis (IPA). Results After adjusting for multiple comparisons, a significant interaction of the chemokine signaling pathway with obesity (P = 3.29 × 10−6) and a near significant interaction of calcium signaling pathway with diabetes (P = 1.57 × 10−4) in modifying the risk of pancreatic cancer was observed. These findings were supported by results from IPA analysis of the top genes with nominal interactions. The major contributing genes to the two top pathways include GNGT2, RELA, TIAM1 and GNAS. None of the individual genes or SNPs except one SNP remained significant after adjusting for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an interaction with diabetes (P = 7.91 × 10−7) at a false discovery rate of 6%. Conclusions Genetic variations in inflammatory response and insulin resistance may affect the risk of obesity and diabetes-related pancreatic cancer. These observations should be replicated in additional large datasets. Impact Gene-environment interaction analysis may provide new insights into the genetic susceptibility and molecular mechanisms of obesity- and diabetes-related pancreatic cancer. PMID:24136929

  2. Averting Obesity and Type 2 Diabetes in India through Sugar-Sweetened Beverage Taxation: An Economic-Epidemiologic Modeling Study

    PubMed Central

    Basu, Sanjay; Vellakkal, Sukumar; Agrawal, Sutapa; Stuckler, David; Popkin, Barry; Ebrahim, Shah

    2014-01-01

    Background Taxing sugar-sweetened beverages (SSBs) has been proposed in high-income countries to reduce obesity and type 2 diabetes. We sought to estimate the potential health effects of such a fiscal strategy in the middle-income country of India, where there is heterogeneity in SSB consumption, patterns of substitution between SSBs and other beverages after tax increases, and vast differences in chronic disease risk within the population. Methods and Findings Using consumption and price variations data from a nationally representative survey of 100,855 Indian households, we first calculated how changes in SSB price alter per capita consumption of SSBs and substitution with other beverages. We then incorporated SSB sales trends, body mass index (BMI), and diabetes incidence data stratified by age, sex, income, and urban/rural residence into a validated microsimulation of caloric consumption, glycemic load, overweight/obesity prevalence, and type 2 diabetes incidence among Indian subpopulations facing a 20% SSB excise tax. The 20% SSB tax was anticipated to reduce overweight and obesity prevalence by 3.0% (95% CI 1.6%–5.9%) and type 2 diabetes incidence by 1.6% (95% CI 1.2%–1.9%) among various Indian subpopulations over the period 2014–2023, if SSB consumption continued to increase linearly in accordance with secular trends. However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5–10.0%) and 2.5% (95% CI 1.0–2.8%) of incident type 2 diabetes from 2014–2023. Given current consumption and BMI distributions, our results suggest the largest relative effect would be expected among young rural men, refuting our a priori hypothesis that urban populations would be isolated beneficiaries of SSB taxation. Key limitations of this estimation approach include the assumption that consumer expenditure behavior from

  3. Diabetes and Pre-Diabetes among Persons Aged 35 to 60 Years in Eastern Uganda: Prevalence and Associated Factors

    PubMed Central

    Mayega, Roy William; Guwatudde, David; Makumbi, Fredrick; Nakwagala, Frederick Nelson; Peterson, Stefan; Tomson, Goran; Ostenson, Claes-Goran

    2013-01-01

    Background Our aim was to estimate the prevalence of abnormal glucose regulation (AGR) (i.e. diabetes and pre-diabetes) and its associated factors among people aged 35-60 years so as to clarify the relevance of targeted screening in rural Africa. Methods A population-based survey of 1,497 people (786 women and 711 men) aged 35-60 years was conducted in a predominantly rural Demographic Surveillance Site in eastern Uganda. Participants responded to a lifestyle questionnaire, following which their Body Mass Index (BMI) and Blood Pressure (BP) were measured. Fasting plasma glucose (FPG) was measured from capillary blood using On-Call® Plus (Acon) rapid glucose meters, following overnight fasting. AGR was defined as FPG ≥6.1mmol L-1 (World Health Organization (WHO) criteria or ≥5.6mmol L-1 (American Diabetes Association (ADA) criteria. Diabetes was defined as FPG >6.9mmol L-1, or being on diabetes treatment. Results The mean age of participants was 45 years for men and 44 for women. Prevalence of diabetes was 7.4% (95%CI 6.1-8.8), while prevalence of pre-diabetes was 8.6% (95%CI 7.3-10.2) using WHO criteria and 20.2% (95%CI 17.5-22.9) with ADA criteria. Using WHO cut-offs, the prevalence of AGR was 2 times higher among obese persons compared with normal BMI persons (Adjusted Prevalence Rate Ratio (APRR) 1.9, 95%CI 1.3-2.8). Occupation as a mechanic, achieving the WHO recommended physical activity threshold, and higher dietary diversity were associated with lower likelihood of AGR (APRR 0.6, 95%CI 0.4-0.9; APRR 0.6, 95%CI 0.4-0.8; APRR 0.5, 95%CI 0.3-0.9 respectively). The direct medical cost of detecting one person with AGR was two US dollars with ADA and three point seven dollars with WHO cut-offs. Conclusions There is a high prevalence of AGR among people aged 35-60 years in this setting. Screening for high risk persons and targeted health education to address obesity, insufficient physical activity and non-diverse diets are necessary. PMID:23967317

  4. Chronic Ingestion of Advanced Glycation End Products Induces Degenerative Spinal Changes and Hypertrophy in Aging Pre-Diabetic Mice

    PubMed Central

    Illien-Jünger, Svenja; Lu, Young; Qureshi, Sheeraz A.; Hecht, Andrew C.; Cai, Weijing; Vlassara, Helen; Striker, Gary E.; Iatridis, James C.

    2015-01-01

    Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions. PMID:25668621

  5. Amylase/creatinine clearance ratio response to hyperglucagonemia in diabetes and obesity.

    PubMed

    Kanter, Y; Piell, E; Santo, M

    1986-11-01

    Hyperglucagonemia accompanies several disorders such as acute pancreatitis and diabetic ketoacidosis characterized by increased amylase/creatinine clearance ratio (ACCR). We tested the hypothesis that glucagon may be responsible for the augmental ACCR among diabetic and/or obese subjects. A constant glucagon infusion (15 ng/kg/min) was given to eight noninsulin-dependent diabetics and to eight obese subjects to attain glucagon levels comparable with those obtained during acute pancreatitis. The ACCR significantly increased from 0.9 +/- 0.1 to 1.5 +/- 0.1% (p less than 0.005) in both noninsulin-dependent diabetics and obese subjects, whereas among normal control subjects the ACCR increased from 0.84 +/- 0.8 to 1.3 +/- 0.14% (p less than 0.001). Because the increased values observed in either noninsulin-dependent diabetics or obese subjects are less than the ACCR values observed in acute pancreatitis or in diabetic ketoacidosis, the elevated ACCR in those conditions is only partially explained by the hyperglucagonemia.

  6. Amylase/creatinine clearance ratio response to hyperglucagonemia in diabetes and obesity.

    PubMed

    Kanter, Y; Piell, E; Santo, M

    1986-11-01

    Hyperglucagonemia accompanies several disorders such as acute pancreatitis and diabetic ketoacidosis characterized by increased amylase/creatinine clearance ratio (ACCR). We tested the hypothesis that glucagon may be responsible for the augmental ACCR among diabetic and/or obese subjects. A constant glucagon infusion (15 ng/kg/min) was given to eight noninsulin-dependent diabetics and to eight obese subjects to attain glucagon levels comparable with those obtained during acute pancreatitis. The ACCR significantly increased from 0.9 +/- 0.1 to 1.5 +/- 0.1% (p less than 0.005) in both noninsulin-dependent diabetics and obese subjects, whereas among normal control subjects the ACCR increased from 0.84 +/- 0.8 to 1.3 +/- 0.14% (p less than 0.001). Because the increased values observed in either noninsulin-dependent diabetics or obese subjects are less than the ACCR values observed in acute pancreatitis or in diabetic ketoacidosis, the elevated ACCR in those conditions is only partially explained by the hyperglucagonemia. PMID:2430451

  7. Diabetes, Metabolic Syndrome, and Obesity in Relation to Serum Dioxin Concentrations: The Seveso Women’s Health Study

    PubMed Central

    Mocarelli, Paolo; Brambilla, Paolo; Wesselink, Amelia; Samuels, Steven; Signorini, Stefano; Eskenazi, Brenda

    2013-01-01

    Background: In animal studies, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters glucose transport and increases serum lipid levels and blood pressure. Epidemiologic evidence suggests an association between TCDD and metabolic disease. Objectives: On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential exposure to TCDD. Using data from the Seveso Women’s Health Study (SWHS), a cohort study of the health of the women, we examined the relation of serum TCDD to diabetes, metabolic syndrome, and obesity > 30 years later. Methods: In 1996, we enrolled 981 women who were newborn to 40 years of age in 1976 and resided in the most contaminated areas. Individual TCDD concentration was measured in archived serum that had been collected soon after the explosion. In 2008, 833 women participated in a follow-up study. Diabetes was classified based on self-report or fasting serum glucose and glycated hemoglobin levels. Metabolic syndrome was defined by International Diabetes Federation criteria. Obesity was defined as body mass index ≥ 30 kg/m2. Results: A 10-fold increase in serum TCDD (log10TCDD) was not associated with diabetes (adjusted hazard ratio = 0.76; 95% CI: 0.45, 1.28) or obesity [adjusted odds ratio (OR) = 0.80; 95% CI: 0.58, 1.10]. Log10TCDD was associated with metabolic syndrome, but only among women who were ≤ 12 years of age at the time of the explosion (adjusted OR = 2.03; 95% CI: 1.25, 3.29; pinteraction = 0.01). Conclusions: We found an increased prevalence of metabolic syndrome associated with TCDD, but only among women who were the youngest at the time of the explosion. Continued follow-up of the SWHS cohort will be informative. PMID:23674506

  8. Risk of obesity at 4 to 6 years of age among overweight or obese 18-month-olds

    PubMed Central

    Wheeler, Jesse J.

    2013-01-01

    Abstract Objective To determine whether high weight for length at the 18-month well-baby visit is predictive of overweight or obese body mass index (BMI) at the 4- to 6-year well-child visit. Design Retrospective cohort study using objective electronic medical record measurements. Setting Eighteen family practices forming a community family health organization in Peterborough, Ont. Participants All children from the family health organization practices with at least 1 set of weight and length or height measurements at age 17 to 19 months and age 4 to 6 years (N = 126). Main outcome measure Relative risk (RR) of overweight BMI and RR of obese BMI at 4 to 6 years of age for normal versus overweight or obese 18-month-olds. Results Children who were either overweight or obese at their 18-month visits (n = 37) were more than twice as likely to be obese at age 4 to 6 years than children who had healthy weights at 18 months were (n = 89; RR = 2.71, 95% CI 1.13 to 6.47). The subgroup of obese 18-month-olds (n = 13) were at more than 3 times the risk of being obese at age 4 to 6 years than their healthy-weight-for-length counterparts (RR = 3.42, 95% CI 1.20 to 9.78). Thirty-one percent of obese 18-month-olds were obese at 4 to 6 years and a further 31% were overweight. Conclusion High weight for length at 18 months substantially increased a child’s risk of being overweight or obese at 4 to 6 years of age. Most overweight and obese 18-month-olds in this study did not achieve healthy BMIs by 4 to 6 years of age. A brief glance at the 18-month weight-for-length chart can easily help identify these high-risk toddlers. PMID:23585624

  9. Is Acanthosis Nigricans a Reliable Indicator for Risk of Type 2 Diabetes in Obese Children and Adolescents?: A Systematic Review

    ERIC Educational Resources Information Center

    Abraham, Cilymol; Rozmus, Cathy L.

    2012-01-01

    Obesity and type 2 diabetes is becoming a major health problem affecting children and adolescents in the United States. This article reviews the current literature examining the association between the presence of acanthosis nigricans (AN) and risk for developing type 2 diabetes mellitus (T2DM) in obese children and adolescents. Ethnicity, family…

  10. Environmentally Driven Increases in Type 2 Diabetes and Obesity in Pima Indians and Non-Pimas in Mexico Over a 15-Year Period: The Maycoba Project

    PubMed Central

    Esparza-Romero, Julian; Valencia, Mauro E.; Urquidez-Romero, Rene; Chaudhari, Lisa S.; Knowler, William C.; Ravussin, Eric; Bennett, Peter H.

    2015-01-01

    OBJECTIVE The global epidemics of type 2 diabetes and obesity have been attributed to the interaction between lifestyle changes and genetic predisposition to these diseases. We compared the prevalences of type 2 diabetes and obesity in Mexican Pima Indians, presumed to have a high genetic predisposition to these diseases, to those in their non-Pima neighbors, both of whom over a 15-year period experienced a transition from a traditional to a more modern lifestyle. RESEARCH DESIGN AND METHODS Prevalence of diabetes, impaired fasting glucose, impaired glucose tolerance, and obesity in Mexican Pimas (n = 359) and non-Pima Mexicans (n = 251) were determined in 2010 using methods identical to those used in 1995. RESULTS During this 15-year period, age-adjusted diabetes prevalence was unchanged in Pima men (5.8% in 1995 vs. 6.1% in 2010) yet increased in non-Pima men from 0.0 to 8.6% (P < 0.05). Diabetes prevalence tended to increase in both Pima women (9.4 vs. 13.4%) and non-Pima women (4.8 vs. 9.5%). Age-adjusted prevalence of obesity increased significantly in all groups (6.6 vs. 15.7% in Pima men; 8.5 vs. 20.5% in non-Pima men; 18.9. vs 36.3% in Pima women; 29.5 vs. 42.9% in non-Pima women). CONCLUSIONS Type 2 diabetes prevalence increased between 1995 and 2010 in non-Pima men, and to a lesser degree in women of both groups, but it did not increase in Pima men. Prevalence of obesity increased among Pimas and non-Pimas of both sexes. These changes occurred concomitantly with an environmental transition from a traditional to a more modernized lifestyle. PMID:26246457

  11. The role of Gut Microbiota in the development of obesity and Diabetes.

    PubMed

    Baothman, Othman A; Zamzami, Mazin A; Taher, Ibrahim; Abubaker, Jehad; Abu-Farha, Mohamed

    2016-01-01

    Obesity and its associated complications like type 2 diabetes (T2D) are reaching epidemic stages. Increased food intake and lack of exercise are two main contributing factors. Recent work has been highlighting an increasingly more important role of gut microbiota in metabolic disorders. It's well known that gut microbiota plays a major role in the development of food absorption and low grade inflammation, two key processes in obesity and diabetes. This review summarizes key discoveries during the past decade that established the role of gut microbiota in the development of obesity and diabetes. It will look at the role of key metabolites mainly the short chain fatty acids (SCFA) that are produced by gut microbiota and how they impact key metabolic pathways such as insulin signalling, incretin production as well as inflammation. It will further look at the possible ways to harness the beneficial aspects of the gut microbiota to combat these metabolic disorders and reduce their impact. PMID:27317359

  12. Obesity and diabetes, the built environment, and the 'local' food economy in the United States, 2007.

    PubMed

    Salois, Matthew J

    2012-01-01

    Obesity and diabetes are increasingly attributed to environmental factors, however, little attention has been paid to the influence of the 'local' food economy. This paper examines the association of measures relating to the built environment and 'local' agriculture with U.S. county-level prevalence of obesity and diabetes. Key indicators of the 'local' food economy include the density of farmers' markets and the presence of farms with direct sales. This paper employs a robust regression estimator to account for non-normality of the data and to accommodate outliers. Overall, the built environment is associated with the prevalence of obesity and diabetes and a strong local' food economy may play an important role in prevention. Results imply considerable scope for community-level interventions.

  13. Serum adiponectin levels in diabetes, obesity and gender in Punjabi subjects from Faisalabad, Pakistan.

    PubMed

    Najam, Syeda Sadia; Awan, Fazli Rabbi; Baig, Shahid Mahmood

    2014-10-01

    Adiponectin has been associated with common metabolic disorders. The current study was conducted to measure and compare levels of adiponectin with obesity, type 2 diabetes mellitus (T2DM) and gender in Punjabi subjects from Faisalabad, Pakistan. Serum adiponectin was measured by enzyme-linked immunosorbent assay (ELISA) along with measurements of some clinically important analytes (fasting blood glucose, cholesterol, triglycerides) as well as body mass index (BMI) in 80 subjects. The main results were significantly (p < 0.003) decreased serum adiponectin level in T2DM patients (n = 40) compared to non-diabetic controls (n = 40). In obese subjects, (n = 40) also, there was a decrease, but it was not significant. Adiponectin levels in the subgroups of diabetic and obese patients were also observed, but no significant gender-based differences were found.

  14. Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats.

    PubMed

    Phyu, Hnin Ei; Irwin, Jordon Candice; Vella, Rebecca Kate; Fenning, Andrew Stuart

    2016-06-01

    Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia. The aim of this study was to determine whether resveratrol, a polyphenol antioxidant compound, when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older, obese, diabetic rats. Diabetes was induced in 6-month old, obese, male Wistar rats via a single intravenous dose of streptozotocin (65 mg/kg). Randomly selected animals were administered resveratrol (2 mg/kg) via oral gavage daily for 8 weeks. Body weights, blood glucose levels, food intake and water consumption were monitored, and assessments of vascular reactivity, tactile allodynia and left ventricular function were performed. Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats (P<0·05). There were no significant changes in standardised vasorelaxation responses, plasma glucose concentrations, water consumption, body weight, left ventricular hypertrophy, kidney hypertrophy, heart rate or left ventricular compliance with resveratrol administration. Resveratrol-mediated improvements in vascular and nerve function in old, obese, diabetic rats were associated with its reported antioxidant effects. Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus (i.e. hyperglycaemia, polydypsia and a failure to thrive). This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus.

  15. Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats.

    PubMed

    Phyu, Hnin Ei; Irwin, Jordon Candice; Vella, Rebecca Kate; Fenning, Andrew Stuart

    2016-06-01

    Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia. The aim of this study was to determine whether resveratrol, a polyphenol antioxidant compound, when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older, obese, diabetic rats. Diabetes was induced in 6-month old, obese, male Wistar rats via a single intravenous dose of streptozotocin (65 mg/kg). Randomly selected animals were administered resveratrol (2 mg/kg) via oral gavage daily for 8 weeks. Body weights, blood glucose levels, food intake and water consumption were monitored, and assessments of vascular reactivity, tactile allodynia and left ventricular function were performed. Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats (P<0·05). There were no significant changes in standardised vasorelaxation responses, plasma glucose concentrations, water consumption, body weight, left ventricular hypertrophy, kidney hypertrophy, heart rate or left ventricular compliance with resveratrol administration. Resveratrol-mediated improvements in vascular and nerve function in old, obese, diabetic rats were associated with its reported antioxidant effects. Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus (i.e. hyperglycaemia, polydypsia and a failure to thrive). This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus. PMID:27153202

  16. Probit Models to Investigate Prevalence of Total Diagnosed and Undiagnosed Diabetes among Aged 45 Years or Older Adults in China

    PubMed Central

    Yin, Minghui; Augustin, Balekouzou; Shu, Chang; Qin, Tingting; Yin, Ping

    2016-01-01

    The aims of this study are to identify the most important predictors of total diagnosed and undiagnosed diabetes and estimate the mean change in the predicted probability among aged 45+ adults in China. We used baseline data collected from 2011 wave of the China Health and Retirement Longitudinal Study (CHARLS) (n = 9,513). First, we estimated the prevalence of diagnosed, measured, total diagnosed, and undiagnosed diabetes. Second, we used probit models to determine whether individual attributes, socioeconomic characteristics and behavioral health factors, including smoking, alcohol consumption, obesity, central obesity, are associated with total diagnosed and undiagnosed diabetes. We also consider other factors, including contact with medical system, hypertension and urban/rural settings. Third, we estimated average marginal effects of variables in probit models. Among Chinese people aged 45+, the prevalence of diagnosed, measured, total diagnosed and undiagnosed diabetes were 5.8% (95%CI, 5.3%-6.3%), 14.7% (95%CI, 14.0%-15.4%), 17.0% (95%CI, 16.3%-17.7%), 11.3% (95%CI, 10.6%-12.0%), respectively. The probability of total diagnosed diabetes is 3.3% (95% CI, 1.2%-5.3%) and 10.2% (95% CI, 7.0%-13.5%) higher for overweight and obesity than normal BMI, 5.0% (95% CI, 3.0%-7.1%) higher for central obesity than normal waist circumference, 5.4% (95% CI, 3.7%-7.0%) higher for hypertensive than normotensive and 1.8% (95% CI, 0.8%- 2.7%) higher in urban areas than in rural areas, respectively. The probability of undiagnosed diabetes is 2.7% (95% CI, 1.2%-4.2%) and 7.2% (95% CI, 4.7%-9.6%) higher for overweight and obesity than normal BMI, 2.6% (95% CI, 0.9%-4.4%) higher for central obesity than normal waist circumference and 2.6% (95% CI, 1.2%-4.0%) higher for hypertensive than normotensive, respectively, and -1.5% (95% CI, -2.5% to -0.5%) lower for individuals who were in contact with the medical system. Greater focus on prevention of diabetes is necessary for obesity

  17. Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes.

    PubMed

    Fukushima, Arata; Lopaschuk, Gary D

    2016-10-01

    Obesity and diabetes are major public health problems, and are linked to the development of heart failure. Emerging data highlight the importance of alterations in cardiac energy metabolism as a major contributor to cardiac dysfunction related to obesity and diabetes. Increased rates of fatty acid oxidation and decreased rates of glucose utilization are two prominent changes in cardiac energy metabolism that occur in obesity and diabetes. This metabolic profile is probably both a cause and consequence of a prominent cardiac insulin resistance, which is accompanied by a decrease in both cardiac function and efficiency, and by the accumulation of potentially toxic lipid metabolites in the heart that can further exaggerate insulin resistance and cardiac dysfunction. The high cardiac fatty acid oxidation rates seen in obesity and diabetes are attributable to several factors, including: 1) increased fatty acid supply and uptake into the cardiomyocyte, 2) increased transcription of fatty acid metabolic enzymes, 3) decreased allosteric control of mitochondrial fatty acid uptake and fatty acid oxidation, and 4) increased post-translational acetylation control of various fatty acid oxidative enzymes. Emerging evidence suggests that therapeutic approaches aimed at switching the balance of cardiac energy substrate preference from fatty acid oxidation to glucose use can prevent cardiac dysfunction associated with obesity and diabetes. Modulating acetylation control of fatty acid oxidative enzymes is also a potentially attractive strategy, although presently this is limited to precursors of nicotinamide adenine or nonspecific activators of deacetylation such as resveratrol. This review will focus on the metabolic alterations in the heart that occur in obesity and diabetes, as well as on the molecular mechanisms controlling these metabolic changes. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26996746

  18. Do Interactions Between Gut Ecology and Environmental Chemicals Contribute to Obesity and Diabetes?

    PubMed Central

    Snedeker, Suzanne M.

    2011-01-01

    Background: Gut microbiota are important factors in obesity and diabetes, yet little is known about their role in the toxicodynamics of environmental chemicals, including those recently found to be obesogenic and diabetogenic. Objectives: We integrated evidence that independently links gut ecology and environmental chemicals to obesity and diabetes, providing a framework for suggesting how these environmental factors may interact with these diseases, and identified future research needs. Methods: We examined studies with germ-free or antibiotic-treated laboratory animals, and human studies that evaluated how dietary influences and microbial changes affected obesity and diabetes. Strengths and weaknesses of studies evaluating how environmental chemical exposures may affect obesity and diabetes were summarized, and research gaps on how gut ecology may affect the disposition of environmental chemicals were identified. Results: Mounting evidence indicates that gut microbiota composition affects obesity and diabetes, as does exposure to environmental chemicals. The toxicology and pharmacology literature also suggests that interindividual variations in gut microbiota may affect chemical metabolism via direct activation of chemicals, depletion of metabolites needed for biotransformation, alteration of host biotransformation enzyme activities, changes in enterohepatic circulation, altered bioavailability of environmental chemicals and/or antioxidants from food, and alterations in gut motility and barrier function. Conclusions: Variations in gut microbiota are likely to affect human toxicodynamics and increase individual exposure to obesogenic and diabetogenic chemicals. Combating the global obesity and diabetes epidemics requires a multifaceted approach that should include greater emphasis on understanding and controlling the impact of interindividual gut microbe variability on the disposition of environmental chemicals in humans. PMID:22042266

  19. Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes.

    PubMed

    Fukushima, Arata; Lopaschuk, Gary D

    2016-10-01

    Obesity and diabetes are major public health problems, and are linked to the development of heart failure. Emerging data highlight the importance of alterations in cardiac energy metabolism as a major contributor to cardiac dysfunction related to obesity and diabetes. Increased rates of fatty acid oxidation and decreased rates of glucose utilization are two prominent changes in cardiac energy metabolism that occur in obesity and diabetes. This metabolic profile is probably both a cause and consequence of a prominent cardiac insulin resistance, which is accompanied by a decrease in both cardiac function and efficiency, and by the accumulation of potentially toxic lipid metabolites in the heart that can further exaggerate insulin resistance and cardiac dysfunction. The high cardiac fatty acid oxidation rates seen in obesity and diabetes are attributable to several factors, including: 1) increased fatty acid supply and uptake into the cardiomyocyte, 2) increased transcription of fatty acid metabolic enzymes, 3) decreased allosteric control of mitochondrial fatty acid uptake and fatty acid oxidation, and 4) increased post-translational acetylation control of various fatty acid oxidative enzymes. Emerging evidence suggests that therapeutic approaches aimed at switching the balance of cardiac energy substrate preference from fatty acid oxidation to glucose use can prevent cardiac dysfunction associated with obesity and diabetes. Modulating acetylation control of fatty acid oxidative enzymes is also a potentially attractive strategy, although presently this is limited to precursors of nicotinamide adenine or nonspecific activators of deacetylation such as resveratrol. This review will focus on the metabolic alterations in the heart that occur in obesity and diabetes, as well as on the molecular mechanisms controlling these metabolic changes. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk.

  20. Maternal dietary n-6/n-3 fatty acid ratio affects type 1 diabetes development in the offspring of non-obese diabetic mice.

    PubMed

    Kagohashi, Yukiko; Abiru, Norio; Kobayashi, Masakazu; Hashimoto, Michio; Shido, Osamu; Otani, Hiroki

    2010-12-01

    Environment factors, including maternal or infant dietary nutrition have been reported to have an influence on the pathogenesis of type 1 diabetes. In the present study, to investigate the effect of maternal or post-weaning offspring's nutrition, in particular the essential fatty acid ratio (n-6/n-3) on the development of type 1 diabetes, we prepared two kinds of chows with n-6/n-3 ratios of 3.0 (L) and 14.5 (H), and provided them to mothers of non-obese diabetic (NOD) mice during gestation and lactation and to the offspring after weaning. The n-6/n-3 ratios in breast milk and erythrocyte membrane of NOD offspring became nearly the same with that of the maternal diet at 2 weeks after birth. In the L chow-fed offspring from L chow-fed mother (LLL), levels of insulitis were higher than those in the H chow-fed offspring from H chow-fed mother (HHH) at 4 weeks of age, while the levels in the LLL offspring became lower than those in the HHH after 6 weeks. Early insulin autoantibody expressions were found from 2 to 6 weeks in the HHH offspring, but not in the LLL. The LLL offspring exhibited strong suppression of overt diabetes development in regard to the onset and accumulated incidence of diabetes compared to the HHH. The study with combined L and H chows during gestation, lactation in mother and in post-weaning offspring revealed that only the LLH chow significantly suppressed the development of diabetes with similar kinetics to LLL chow, although the other combinations may delay the onset of diabetes. The present findings suggest that n-6/n-3 ratio of the maternal diet during gestation and lactation rather than that of offspring after weaning strongly affects the development of overt diabetes in NOD mice. PMID:20846138

  1. [New markers of progression of chronic heart failure in patients with myocardial infarction, type 2 diabetes and obesity].

    PubMed

    Kravchun, P P; Kadykova, O I; Gabisonia, T N

    2015-01-01

    Currently identified a large number of biomarkers that are closely linked with the development of chronic heart failure, some of which are clusterin and fractalkine. Accordingly, the purpose of our study was - to evaluate the role of clusterin and fractalkine in progression of chronic heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. We investigated 71 patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. All patients with postinfarction cardiosclerosis, diabetes and obesity were divided into groups according to the functional class of chronic heart failure (CHF). It was found that an increase the level of fractalkine and reduced clusterin leads due to the development of systolic dysfunction and heart failure progression in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. Fractalkine and clusterin play an important role in progression of the heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity, and this gives them the right to be considered indicators of the severity of CHF.

  2. Metabolic asthma: is there a link between obesity, diabetes, and asthma?

    PubMed

    Perez, Miriam K; Piedimonte, Giovanni

    2014-11-01

    Childhood asthma and obesity have reached epidemic proportions worldwide, and the latter is also contributing to increasing rates of related metabolic disorders, such as diabetes. However, the relationship between asthma, obesity, and abnormal metabolism is not well understood nor has it been adequately explored in children. This article discusses the concept of metabolic asthma and the recent hypothesis that early derangement in lipid and glucose metabolism is independently associated with increased risk for asthma. PMID:25282290

  3. Renal outcomes of bariatric surgery in obese adults with diabetic kidney disease.

    PubMed

    Rao, Bhavana B; Bhattacharya, Abhik; Agrawal, Varun

    2014-08-01

    Obesity is a pandemic with several significant adverse health outcomes. Chronic kidney disease has been an overlooked consequence of obesity. Among diabetics, obesity is known to amplify the risk for kidney disease. Although bariatric surgery promises significant and sustained weight reduction with favorable impact on metabolic parameters such as glycemic control, hypertension and dyslipidemia, its impact on the renal complications of diabetes is poorly understood. This paper aims to comprehensively evaluate the evidence in the published literature on the impact of bariatric surgery on renal outcomes in obese adults with diabetic kidney disease. While many observational studies have demonstrated significant reduction in proteinuria after bariatric surgery, there is paucity of data regarding changes in renal filtration function such as doubling of serum creatinine or progression to end stage kidney disease. No randomized controlled trials comparing medical vs. surgical therapy in obese adults with diabetic kidney disease exist, hence assessing the metabolic benefits vs. the surgical risks is important before recommending bariatric surgery to this growing patient population. Future studies require a collaborative effort between bariatric surgeons and nephrologists to measure long-term effects of bariatric surgery on renal outcomes incorporating evolving markers of kidney injury to advance this field.

  4. [Prevention and nutrition related illnesses. Obesity, diabetes mellitus].

    PubMed

    Müller, M J; Danielzik, S

    2004-02-01

    Faced with the obesity epidemic there is need for therapy as well as public health strategies for health promotion and obesity prevention. Both strategies add to each other, none should be done in isolation. Obesity is not only an individual problem. It is also a problem of our society. We are now an overweight society, which is on the way to a fat society. There is urgent need for a national public health strategy for population wide prevention of overweight and obesity. Health authorities as well as politicians are asked to support public health strategies creating a supportive environment for making healthy choices the easier choices.

  5. Faecalibacterium prausnitzii phylotypes in type two diabetic, obese, and lean control subjects.

    PubMed

    Hippe, B; Remely, M; Aumueller, E; Pointner, A; Magnet, U; Haslberger, A G

    2016-09-01

    Faecalibacterium prausnitzii is one of the main butyrate producers in the healthy human gut. Information on its genetic diversity is lacking, although two genetic phylotypes have been differentiated. In the present study, F. prausnitzii phylotypes were examined in faeces of obese and type two diabetes with similar eating behaviour compared to a lean control group. The purpose of the study was to analyse if an excessive butyrate production induced by different F. prausnitzii phylotypes discriminates between obese developing type two diabetes or not. The faecal samples were analysed for the total abundance of F. prausnitzii 16S rRNA copies, fragment lengths polymorphism, high resolution melt curve analysis (HRM) and the butyryl-CoA:acetate CoA-transferase gene copies and melt curve variances. The diabetic group was found to differ significantly from the lean control group in the results of qPCR, butyryl-CoA:acetyate CoA-transferase gene melt curve, and HRM. F. prausnitzii phylotypes differed in obese with and without developed diabetes type two. Different phylotypes of F. prausnitzii may lead to differences in the inflammatory genesis in the host. F. prausnitzii phylotypes may have an influence on developing type two diabetes and might also act as starting points for prevention and therapy of obesity associated disease.

  6. Association between obesity and depression in patients with diabetes mellitus type 2; a study protocol

    PubMed Central

    De la Cruz-Cano, Eduardo; Tovilla-Zarate, Carlos Alfonso; Reyes-Ramos, Emilio; Gonzalez-Castro, Thelma Beatriz; Juarez-Castro, Isela; López-Narváez, Maria Lilia; Fresan, Ana

    2015-01-01

    Background: Diabetes mellitus and depression are highly prevalent conditions throughout the world and have significant impact on health outcomes. It has been estimated that diabetes mellitus type 2 affects about 246 million people in the world; nevertheless, incidence varies among countries. There is evidence that depression is associated with a poor metabolic control in patients with type 2 diabetes mellitus that present other health problems (such as hypertension and obesity). The aim of this study protocol is to determine if obesity increases the risk for depression in patient with diabetes type 2. Methods: The analysis will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).The studies suitable for inclusion will be assessed by the Newcastle-Ottawa Scale (NOS) to determine their methodological quality. To identify the studies of interest, we will search on PubMed and EBSCO databases. We will use the following keyword combinations: "Diabetes Mellitus type 2 AND obesity AND depression", "depression AND Diabetes Mellitus type 2", "Diabetes Mellitus type 2 AND body mass index cross sectional study", "depression AND obesity cross-sectional study". Causes for exclusion will be publications that studied patients diagnosed with diabetes mellitus type 1; articles that focused on the treatment and complications of diabetes mellitus type 2; publications that have studied other clinical or psychiatric conditions (for instance, seizure disorder or history of schizophrenia, bipolar disorder, psychotic symptoms or dementia). Conclusion: The results of this study will form the basis for a better understanding of the association between obesity and depression in patients with diabetes mellitus type 2, and will allow development of prediction tools and better interventions. It is evident that several modifiable and non-modifiable risk factors play an important role in the pathogenesis of diabetes among population. Currently

  7. Increased Risk for Vitamin D Deficiency in Obese Children with Both Celiac Disease and Type 1 Diabetes

    PubMed Central

    Setty-Shah, Nithya; Nwosu, Benjamin Udoka

    2014-01-01

    Background. It is unknown whether the coexistence of type 1 diabetes (T1D) and celiac disease (CD) increases the risk for vitamin D deficiency. Aims. To determine the vitamin D status and the risk for vitamin D deficiency in prepubertal children with both T1D and CD compared to controls, TID, and CD. Subjects and Methods. Characteristics of 62 prepubertal children of age 2–13 y with either CD + T1D (n = 22, 9.9 ± 3.1 y), CD only (n = 18, 8.9 ± 3.3 y), or T1D only (n = 22, 10.1 ± 2.8 y) were compared to 49 controls of the age of 8.0 ± 2.6 years. Vitamin D deficiency was defined as 25(OH)D < 50 nmol/L, overweight as BMI of >85th but <95th percentile, and obesity as BMI > 95th percentile. Results. The 4 groups had no difference in 25(OH)D (ANOVA P = 0.123) before stratification into normal-weight versus overweight/obese subtypes. Following stratification, 25(OH)D differed significantly between the subgroups (F(3,98) = 10.109, ANOVA P < 0.001). Post-hoc analysis showed a significantly lower 25(OH)D in the overweight/obese CD + T1D compared to the overweight/obese controls (P = 0.039) and the overweight/obese CD (P = 0.003). Subjects with CD + T1D were 3 times more likely to be vitamin D deficient (OR = 3.1 [0.8–11.9], P = 0.098), compared to controls. Conclusions. The coexistence of T1D and CD in overweight/obese prepubertal children may be associated with lower vitamin D concentration. PMID:25548555

  8. Genetic polymorphisms associated with overweight and obesity in uncontrolled Type 2 diabetes mellitus.

    PubMed

    Kasim, Nor Bahirah; Huri, Hasniza Zaman; Vethakkan, Shireene Ratna; Ibrahim, Luqman; Abdullah, Bashar Mudhaffar

    2016-01-01

    Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM. PMID:26999420

  9. A Novel Multidisciplinary Intervention for Long-Term Weight Loss and Glycaemic Control in Obese Patients with Diabetes

    PubMed Central

    Lih, Anna; Pereira, Lorraine; Bishay, Ramy H.; Zang, Johnson; Omari, Abdullah; Kormas, Nic

    2015-01-01

    Introduction. Obesity and diabetes are difficult to treat in public clinics. We sought to determine the effectiveness of the Metabolic Rehabilitation Program (MRP) in achieving long-term weight loss and improving glycaemic control versus “best practice” diabetes clinic (DC) in obese patients using a retrospective cohort study. Methods. Patients with diabetes and BMI > 30 kg/m2 who attended the MRP, which consisted of supervised exercise and intense allied health integration, or the DC were selected. Primary outcomes were improvements in weight and glycaemia with secondary outcomes of improvements in blood pressure and lipid profile at 12 and 30 months. Results. Baseline characteristics of both cohorts (40 MRP and 40 DC patients) were similar at baseline other than age (63 in MRP versus 68 years in DC, P = 0.002). At 12 months, MRP patients lost 7.65 ± 1.74 kg versus 1.76 ± 2.60 kg in the DC group (P < 0.0001) and 9.70 ± 2.13 kg versus 0.98 ± 2.65 kg at 30 months (P < 0.0001). Similarly, MRP patients had significant absolute reductions in %HbA1c at 30 months versus the DC group (−0.86 ± 0.31% versus 0.12% ± 0.33%, P < 0.038), with nonsignificant improvements in lipids and blood pressure in MRP patients. Conclusion. Further research is needed to establish the MRP as an effective strategy for achieving sustained weight loss and improving glycaemic control in obese patients with type 2 diabetes. PMID:25950007

  10. Proportion of gestational diabetes mellitus attributable to overweight and obesity among non-Hispanic black, non-Hispanic white, and Hispanic women in South Carolina.

    PubMed

    Cavicchia, Philip P; Liu, Jihong; Adams, Swann A; Steck, Susan E; Hussey, James R; Daguisé, Virginie G; Hebert, James R

    2014-10-01

    Objective was to estimate race-specific proportions of gestational diabetes mellitus (GDM) attributable to overweight and obesity in South Carolina. South Carolina birth certificate and hospital discharge data were obtained from 2004 to 2006. Women who did not have type 2 diabetes mellitus before pregnancy were classified with GDM if a diagnosis was reported in at least one data source. Relative risks (RR) and 95 % confidence intervals were calculated using the log-binomial model. The modified Mokdad equation was used to calculate population attributable fractions for overweight body mass index (BMI: 25.0-29.9 kg/m(2)), obese (30.0-34.9 kg/m(2)), and extremely obese (≥35 kg/m(2)) women after adjusting for age, gestational weight gain, education, marital status, parity, tobacco use, pre-pregnancy hypertension, and pregnancy hypertension. Overall, the adjusted RR of GDM was 1.6, 2.3, and 2.9 times higher among the overweight, obese, and extremely obese women compared to normal-weight women in South Carolina. RR of GDM for extremely obese women was higher among White (3.1) and Hispanic (3.4) women than that for Black women (2.6). The fraction of GDM cases attributable to extreme obesity was 14.0 % among White, 18.1 % among Black, and 9.6 % among Hispanic women. The fraction of GDM cases attributable to obesity was about 12 % for all racial groups. Being overweight (BMI: 25.0-29.9) explained 8.8, 7.8, and 14.4 % of GDM cases among White, Black, and Hispanic women, respectively. Results indicate a significantly increased risk of GDM among overweight, obese, and extremely obese women. The strength of the association and the proportion of GDM cases explained by excessive weight categories vary by racial/ethnic group.

  11. Advanced glycation end products (AGEs) and diabetic vascular complications.

    PubMed

    Yamagishi, Sho-ichi; Nakamura, Kazuo; Imaizumi, Tsutomu

    2005-02-01

    Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Chronic hyperglycemia is essentially involved in the development and progression of diabetic micro- and macroangiopathy. Among various metabolic derangements implicated in the pathogenesis of diabetic vascular complication, advanced glycation end product (AGE) hypothesis is most compatible with the theory of 'hyperglycemic memory'. In this review, we discuss the molecular mechanisms of diabetic vascular complication, specially focusing on AGEs and their receptor (RAGE) system. Several types of AGE inhibitors and their therapeutic implications in this devastating disorder are also discussed here. PMID:18220586

  12. Low serum amylase and obesity, diabetes and metabolic syndrome: A novel interpretation

    PubMed Central

    Nakajima, Kei

    2016-01-01

    For the last decade, low serum amylase (hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes (regardless of type), and metabolic syndrome, all of which appear to have a common etiology of insufficient insulin action due to insulin resistance and/or diminished insulin secretion. Some clinical studies have shown that salivary amylase may be preferentially decreased in obese individuals, whereas others have revealed that pancreatic amylase may be preferentially decreased in diabetic subjects with insulin dependence. Despite this accumulated evidence, the clinical relevance of serum, salivary, and pancreatic amylase and the underlying mechanisms have not been fully elucidated. In recent years, copy number variations (CNVs) in the salivary amylase gene (AMY1), which range more broadly than the pancreatic amylase gene (AMY2A and AMY2B), have been shown to be well correlated with salivary and serum amylase levels. In addition, low CNV of AMY1, indicating low salivary amylase, was associated with insulin resistance, obesity, low taste perception/satiety, and postprandial hyperglycemia through impaired insulin secretion at early cephalic phase. In most populations, insulin-dependent diabetes is less prevalent (minor contribution) compared with insulin-independent diabetes, and obesity is highly prevalent compared with low body weight. Therefore, obesity as a condition that elicits cardiometabolic diseases relating to insulin resistance (major contribution) may be a common determinant for low serum amylase in a general population. In this review, the novel interpretation of low serum, salivary, and pancreas amylase is discussed in terms of major contributions of obesity, diabetes, and metabolic syndrome. PMID:27022442

  13. Preventive effect of Terminalia bellirica on obesity and metabolic disorders in spontaneously obese type 2 diabetic model mice.

    PubMed

    Makihara, Hiroko; Shimada, Tsutomu; Machida, Eriko; Oota, Masatomi; Nagamine, Rika; Tsubata, Masahito; Kinoshita, Kaoru; Takahashi, Kunio; Aburada, Masaki

    2012-07-01

    Visceral obesity induces insulin resistance and is recognized as an important risk factor for metabolic syndrome (MS). Therefore, inhibition of lipid absorption from the intestine is regarded as an effective way of preventing MS. Terminalia bellirica is extensively used in Ayurvedic medicine in India and neighboring countries, and the fruit of this plant has been reported to have hypoglycemic and hypolipidemic effects. In this study, we investigated the preventive effect of a hot water extract of T. bellirica fruit (TB) on obesity and various metabolic disorders, and explored its molecular mechanisms and active ingredients. TB treatment had a preventive effect on obesity, insulin resistance, and hyperlipidemia in spontaneously obese type 2 diabetic TSOD mice. To clarify the molecular mechanisms of TB in preventing obesity, we investigated the inhibitory effect on lipid absorption. TB suppressed absorption of triacylglycerol in an olive oil loading test (in vivo) and showed a strong inhibitory effect on pancreatic lipase activity (in vitro). Furthermore, a search for the active ingredients in TB revealed that gallic acid is the component primarily responsible for the inhibition of pancreatic lipase activity. Thus, our findings indicate that TB could be useful in preventing MS. The mechanisms probably involve suppression of the absorption of meal-derived lipids mediated by gallic acid. PMID:22105160

  14. Microbiota and epigenetic regulation of inflammatory mediators in type 2 diabetes and obesity.

    PubMed

    Remely, M; Aumueller, E; Jahn, D; Hippe, B; Brath, H; Haslberger, A G

    2014-03-01

    Metabolic syndrome is associated with alterations in the structure of the gut microbiota leading to low-grade inflammatory responses. An increased penetration of the impaired gut membrane by bacterial components is believed to induce this inflammation, possibly involving epigenetic alteration of inflammatory molecules such as Toll-like receptors (TLRs). We evaluated changes of the gut microbiota and epigenetic DNA methylation of TLR2 and TLR4 in three groups of subjects: type 2 diabetics under glucagon-like peptide-1 agonist therapy, obese individuals without established insulin resistance, and a lean control group. Clostridium cluster IV, Clostridium cluster XIVa, lactic acid bacteria, Faecalibacterium prausnitzii and Bacteroidetes abundances were analysed by PCR and 454 high-throughput sequencing. The epigenetic methylation in the regulatory region of TLR4 and TLR2 was analysed using bisulfite conversion and pyrosequencing. We observed a significantly higher ratio of Firmicutes/ Bacteroidetes in type 2 diabetics compared to lean controls and obese. Major differences were shown in lactic acid bacteria, with the highest abundance in type 2 diabetics, followed by obese and lean participants. In comparison, F. prausnitzii was least abundant in type 2 diabetics, and most abundant in lean controls. Methylation analysis of four CpGs in the first exon of TLR4 showed significantly lower methylation in obese individuals, but no significant difference between type 2 diabetics and lean controls. Methylation of seven CpGs in the promoter region of TLR2 was significantly lower in type 2 diabetics compared to obese subjects and lean controls. The methylation levels of both TLRs were significantly correlated with body mass index. Our data suggest that changes in gut microbiota and thus cell wall components are involved in the epigenetic regulation of inflammatory reactions. An improved diet targeted to induce gut microbial balance and in the following even epigenetic changes of

  15. Obesity-Related Genomic Loci Are Associated with Type 2 Diabetes in a Han Chinese Population

    PubMed Central

    Zhao, Qi; He, Jiang; Chen, Li; Zhao, Zhigang; Li, Qiang; Ge, Jiapu; Chen, Gang; Guo, Xiaohui; Lu, Juming; Weng, Jianping; Jia, Weiping; Ji, Linong; Xiao, Jianzhong; Shan, Zhongyan; Liu, Jie; Tian, Haoming; Ji, Qiuhe; Zhu, Dalong; Zhou, Zhiguang; Shan, Guangliang; Yang, Wenying

    2014-01-01

    Background and Aims Obesity is a well-known risk factor for type 2 diabetes. Genome-wide association studies have identified a number of genetic loci associated with obesity. The aim of this study is to examine the contribution of obesity-related genomic loci to type 2 diabetes in a Chinese population. Methods We successfully genotyped 18 obesity-related single nucleotide polymorphisms among 5338 type 2 diabetic patients and 4663 controls. Both individual and joint effects of these single nucleotide polymorphisms on type 2 diabetes and quantitative glycemic traits (assessing β-cell function and insulin resistance) were analyzed using logistic and linear regression models, respectively. Results Two single nucleotide polymorphisms near MC4R and GNPDA2 genes were significantly associated with type 2 diabetes before adjusting for body mass index and waist circumference (OR (95% CI) = 1.14 (1.06, 1.22) for the A allele of rs12970134, P = 4.75×10−4; OR (95% CI) = 1.10 (1.03, 1.17) for the G allele of rs10938397, P = 4.54×10−3). When body mass index and waist circumference were further adjusted, the association of MC4R with type 2 diabetes remained significant (P = 1.81×10−2) and that of GNPDA2 was attenuated (P = 1.26×10−1), suggesting the effect of the locus including GNPDA2 on type 2 diabetes may be mediated through obesity. Single nucleotide polymorphism rs2260000 within BAT2 was significantly associated with type 2 diabetes after adjusting for body mass index and waist circumference (P = 1.04×10−2). In addition, four single nucleotide polymorphisms (near or within SEC16B, BDNF, MAF and PRL genes) showed significant associations with quantitative glycemic traits in controls even after adjusting for body mass index and waist circumference (all P values<0.05). Conclusions This study indicates that obesity-related genomic loci were associated with type 2 diabetes and glycemic traits in the Han Chinese population. PMID:25093408

  16. Effect of diet therapy on maximum aerobic power in obese, hyperglycaemic men with recently diagnosed type 2 diabetes.

    PubMed

    Vanninen, E; Uusitupa, M; Siitonen, O; Laitinen, J; Länsimies, E; Pyörälä, K

    1991-05-01

    To find out the effect of correction of hyperglycaemia on maximum aerobic power and anaerobic threshold, we studied 40 middle-aged obese men with recently diagnosed type 2 diabetes before and after 3 months diet therapy. Respiratory gas exchange was measured during maximal incremental bicycle exercise test with breath-by-breath technique at rest, at anaerobic threshold and at peak exercise. As a whole group, the diabetic men reached higher work load after therapy (+9 +/- 3 W (mean +/- SEM), p less than 0.01). A weak inverse linear correlation was found between the changes in fasting blood glucose and in maximum oxygen uptake (r = -0.29, p less than 0.05). When the patients were divided into two groups according to the median values in the change in fasting blood glucose, only those men with more than 1 mmol l-1 decrease in fasting blood glucose improved maximum oxygen uptake (+124 +/- 55 ml min-1 or +6%, p less than 0.05). Oxygen uptake at anaerobic threshold did not change significantly. These results suggest that the correction of hyperglycaemia by diet therapy may improve maximal aerobic power in obese men with recently diagnosed type 2 diabetes.

  17. Physical activity in prevention and management of obesity and type-2 diabetes.

    PubMed

    Hill, James O; Stuht, Jennifer; Wyatt, Holly R; Regensteiner, Judith G

    2006-01-01

    Obesity and type-2 diabetes can be considered diseases of physical inactivity. Physically activity protects against type-2 diabetes through its positive effects on weight management and on the metabolic pathways involved in glycemic control that are not weight-dependent. Increasing physical activity is one of the most effective strategies both for preventing type-2 diabetes and for managing it once it is present. However, we still face an enormous challenge in getting people to achieve sustainable increases in physical activity. A promising strategy is to get people walking more, starting small and increasing gradually over time.

  18. Implication of corticotropic hormone axis in eating behaviour pattern in obese and type 2 diabetic participants.

    PubMed

    Benbaibeche, Hassiba; Haffaf, El Mahdi; Kacimi, Ghouti; Oudjit, Brahim; Khan, Naim Akhtar; Koceïr, Elhadj Ahmed

    2015-04-28

    In Algeria, eating behaviour has been increasingly deviated from its traditional Mediterranean diet to modern fast food style. The present study examines the interactions between eating behaviour pattern (EBP), corticotropic hormone axis and the metabolic syndrome. Our Algerian population cohort comprised of 410 participants (130 obese, 170 type 2 diabetics and 110 healthy participants). The EBP was evaluated by the Three-Factor Eating Questionnaire test. The anthropometric and metabolic parameters (glucose, TAG, HDL, LDL and cholesterol) and the concentrations of hormones (insulin, adrenocorticotropin hormone (ACTH), cortisol and growth hormone) were determined by biometrics, spectrophotometry and RIA, respectively. Multivariate analyses showed a high correlation between the EBP and the metabolic syndrome, particularly between insulin-resistant state and hypertrophy of visceral adipose tissue. Compared with healthy participants, obese ones showed the hyperphagic type of EBP, i.e. disinhibition and hunger disorders. Conversely, the diabetics showed both the hypophagic and hyperphagic type of EBP. In diabetic and obese participants, cortisol and ACTH secretions were significantly altered, leading to metabolic disorders. The present study confirms the role of EBP in obesity and diabetes. PMID:25782454

  19. INFLUENCE OF TYPE II DIABETES AND OBESITY ON THE DISPOSITION AND ELIMINATION OF TCDD IN MICE

    EPA Science Inventory

    INFLUENCE OF TYPE II DIABETES AND OBESITY ON THE DISPOSTION AND ELIMINATION OF TCDD IN MICE. MJ DeVito', JJ Diliberto', DG Ross', C Emond2, VM Richardson', and LS Birnbaum', 'ETD, NHEERL, ORD, US EPA, RTP, NC, 27711, USA, 2National Research Council.
    One possible explanation fo...

  20. Anti-obesity effects of onion extract in Zucker diabetic fatty rats.

    PubMed

    Yoshinari, Orie; Shiojima, Yoshiaki; Igarashi, Kiharu

    2012-10-22

    Anti-obesity effects of onion extract were determined in obesity and diabetes-prone Zucker diabetic fatty rats by measuring the efficacy of markers concerned with diabetes and obesity. Body and adipose tissue weights in 5% of onion extract-fed group were found to be significantly lower than the control group without onion extract. Fasting blood glucose and HOMA-IR levels were also improved, although the serum insulin and leptin levels did not show any remarkable difference. Serum triglyceride and free fatty acid levels in both the 3% and 5%-fed group were found to be reduced compared to the control group. Additionally the feeding of the onion extract increased the glucose tolerance. These results suggest that dietary onion extract is beneficial for improving diabetes by decreasing lipid levels. We also examined differentiation ability of rat white preadipocyte cells using the onion extract and its sulfur-containing components. Cycloalliin, S-methyl-L-cysteine, S-propyl-L-cysteine sulfoxide, dimethyl trisulfide, especially S-methyl-L-cysteine sulfoxide were reported to be effective in inhibiting formation of oil drop in the cells, suggesting that these compounds may be involved in the anti-obesity effect of the onion extract.

  1. Are Self-Management Interventions Suitable for All? Comparing Obese Versus Nonobese Type 2 Diabetes Patients

    ERIC Educational Resources Information Center

    Kroese, Floor M.; Adriaanse, Marieke A.; De Ridder, Denise T. D.

    2013-01-01

    Objective: The aim of the current study was to compare obese and nonobese type 2 diabetes patients at baseline and after participating in an existing self-management intervention (i.e., "Beyond Good Intentions") on cognitive, self-care, and behavioral measures to examine whether both groups are equally prepared and able to adopt…

  2. [History and development trend of minimally invasive surgical treatment for obesity and diabetes in China].

    PubMed

    Ding, Dan; Zheng, Chengzhu

    2016-08-25

    Obesity and type 2 diabetes mellitus have already become one of the most serious society-facing problems. Since the first report in the 1950s, gastrointestinal surgery has greatly developed as the golden standard in obesity treatment. With the convincing research and evidence, it is found that gastrointestinal surgery not only can cause weight loss, but can relieve, even cure many metabolic diseases associated with obesity, especially for type 2 diabetes mellitus. The operational manners, including adjustable gastric banding, Roux-en-Y gastric bypass, mini gastric bypass, sleeve gastrectomy, etc., are proved to be safe and effective in treating obesity and type 2 diabetes mellitus, and all of these operations can be performed with laparoscopy. Currently, gastrointestinal surgeons are focusing on the operation treatment for type 2 diabetes mellitus, and more and more gastrointestinal operations are applied in many medical centers in China. However, there are a lot of details that need to be standardized. It is believed, with the evolution of surgical technique, standardization of diagnosis and treatment, and breakthrough in the basic research, the metabolic surgery will get more development in the future. PMID:27545461

  3. Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVEdRates of severe obesity (BMI$40 kg/m2) are on the rise, and effective treatment options are needed.We examined the effect of an intensive lifestyle intervention (ILI) on weight loss, cardiovascular disease (CVD) risk, and program adherence in participants with type 2 diabetes who were seve...

  4. Indices of insulin secretion during a liquid mixed-meal test in obese youth with diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  5. Obesity and Gestational Diabetes Mellitus Pathways for Programming in Mouse, Monkey, and Man—Where Do We Go Next? The 2014 Norbert Freinkel Award Lecture.

    PubMed

    Friedman, Jacob E

    2015-08-01

    Obesity and gestational diabetes mellitus continue to increase worldwide and span the spectrum of age, race, ethnicity, and socioeconomic status. Alarmingly, 1 in 10 infants and toddlers is obese, and 1 in 5 youths is both obese and at risk for metabolic syndrome prior to puberty. The mechanisms underlying how poor maternal health imparts risk for future metabolic disease in the offspring are beginning to emerge in deeply phenotyped human and nonhuman primate models. Maternal diet and obesity impact fuels, hormones, and inflammation with powerful effects on fetal metabolic systems. These are accompanied by persistent changes in the infant microbiome and epigenome and in offspring behavior. These results suggest that gestational and lactational dietary exposures are driving health risks in the next generation. Whether maternal diet can prevent changes in the womb to alter infant life-course disease risk is still unknown. Controlled, mechanistic studies to identify interventions are sorely needed for a healthier next generation. PMID:26207051

  6. Obesity and Gestational Diabetes Mellitus Pathways for Programming in Mouse, Monkey, and Man—Where Do We Go Next? The 2014 Norbert Freinkel Award Lecture.

    PubMed

    Friedman, Jacob E

    2015-08-01

    Obesity and gestational diabetes mellitus continue to increase worldwide and span the spectrum of age, race, ethnicity, and socioeconomic status. Alarmingly, 1 in 10 infants and toddlers is obese, and 1 in 5 youths is both obese and at risk for metabolic syndrome prior to puberty. The mechanisms underlying how poor maternal health imparts risk for future metabolic disease in the offspring are beginning to emerge in deeply phenotyped human and nonhuman primate models. Maternal diet and obesity impact fuels, hormones, and inflammation with powerful effects on fetal metabolic systems. These are accompanied by persistent changes in the infant microbiome and epigenome and in offspring behavior. These results suggest that gestational and lactational dietary exposures are driving health risks in the next generation. Whether maternal diet can prevent changes in the womb to alter infant life-course disease risk is still unknown. Controlled, mechanistic studies to identify interventions are sorely needed for a healthier next generation.

  7. Understanding the Effect of Obesity on Fertility Among Reproductive-Age Women.

    PubMed

    Mitchell, Allison; Fantasia, Heidi Collins

    2016-01-01

    Obesity is a major public health concern, and obesity among women of childbearing age can have a negative impact on fertility. The mechanism of action between obesity and infertility is complex and includes hormonal factors, alterations in ovulation, and changes in the menstrual cycle. Maternal obesity has also been linked to spontaneous abortion and poorer maternal and fetal health outcomes. Many interventions exist to help childbearing women achieve a lower body mass index. These include lifestyle modifications (diet/physical activity) and surgical and pharmacologic interventions. This article reviews the pathophysiology of the relationship between obesity and infertility and discusses evidence-based interventions for improving fertility among obese childbearing women. PMID:27520601

  8. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur

    SciTech Connect

    Klebig, M.L.; Woychik, R.P.; Wilkinson, J.E.; Geisler, J.G. |

    1995-05-23

    Mice that carry the lethal yellow (A{sup y}) or viable yellow (A{sup vy}) mutation, two dominant mutations of the agouti (a) gene in mouse chromosome 2, exhibit a phenotype that includes yellow fur, marked obesity, a form of type II diabetes associated with insulin resistance, and an increased susceptibility to tumor development. Molecular analyses of these and several other dominant {open_quotes}obese yellow{close_quotes} a-locus mutations suggested that ectopic expression of the normal agouti protein gives rise to this complex pleiotropic phenotype. We have now tested this hypothesis directly by generating transgenic mice that ectopically express an agouti cDNA clone encoding the normal agouti protein in all tissues examined. Transgenic mice of both sexes have yellow fur, become obese, and develop hyperinsulinemia. In addition, male transgenic mice develop hyperglycemia by 12-20 weeks of age. These results demonstrate conclusively that the ectopic agouti expression is responsible for most, if not all, of the phenotypic traits of the dominant, obese yellow mutants. 42 refs., 5 figs.

  9. Obesity-Related Hormones in Low-Income Preschool-Age Children: Implications for School Readiness

    ERIC Educational Resources Information Center

    Miller, Alison L.; Lumeng, Carey N.; Delproposto, Jennifer; Florek, Brian; Wendorf, Kristin; Lumeng, Julie C.

    2013-01-01

    Mechanisms underlying socioeconomic disparities in school readiness and health outcomes, particularly obesity, among preschool-aged children are complex and poorly understood. Obesity can induce changes in proteins in the circulation that contribute to the negative impact of obesity on health; such changes may relate to cognitive and emotion…

  10. Associations of Child Sexual and Physical Abuse with Obesity and Depression in Middle-Aged Women

    ERIC Educational Resources Information Center

    Rohde, Paul; Ichikawa, Laura; Simon, Gregory E.; Ludman, Evette J.; Linde, Jennifer A.; Jeffery, Robert W.; Operskalski, Belinda H.

    2008-01-01

    Objective: Examine whether (1) childhood maltreatment is associated with subsequent obesity and depression in middle-age; (2) maltreatment explains the associations between obesity and depression; and (3) binge eating or body dissatisfaction mediate associations between childhood maltreatment and subsequent obesity. Methods: Data were obtained…

  11. Iron biology, immunology, aging and obesity: four fields connected by the small peptide hormone, hepcidin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is well-known that obesity and aging have a negative impact on iron status and immune response, but little is known about the additional impact that obesity may have on iron homeostasis and immunity in the elderly. This question is relevant given the rising numbers of elderly obese individuals a...

  12. Assessing the obese diabetic patient for bariatric surgery: which candidate do I choose?

    PubMed Central

    Raffaelli, Marco; Sessa, Luca; Mingrone, Geltrude; Bellantone, Rocco

    2015-01-01

    The worldwide prevalence of type 2 diabetes is rising in association with an increasing frequency of overweight and obesity. Bariatric-metabolic procedures are considered as additional therapeutic options, allowing improved diabetes control in most patients. Multiple factors play in concert to achieve the improvements in diabetic remission observed after bariatric-metabolic surgery. Several studies have demonstrated that bariatric-metabolic surgery is an effective treatment for type 2 diabetes when compared with conventional nonsurgical medical treatment. Because the best results are achievable in patients with a relatively short history of diabetes and less advanced controlled disease, the surgical option could be considered early, especially in morbid obese subjects (BMI ≥35 kg/m2) after failure of medical treatment. Patients with extensive weight loss are more likely to achieve type 2 diabetes remission after bariatric surgery. At present, Roux-en-Y gastric bypass seems the surgical procedure of choice because it has fewer risks than biliopancreatic diversion, and it is associated with higher weight loss and metabolic improvements compared with adjustable gastric banding. Recent evidences regarding the effectiveness of sleeve gastrectomy in diabetes remission have to be confirmed by controlled trials with longer follow-up. PMID:26089694

  13. Metabolic Basis of Ethnic Differences in Diabetes Risk in Overweight and Obese Youth

    PubMed Central

    Alderete, TL; Toledo-Corral, CM; Goran, MI

    2015-01-01

    The global pandemic of childhood obesity has led to increased risk for prediabetes and type 2 diabetes mellitus (T2DM). Studies have shown decreased insulin sensitivity and/or secretion with increasing adiposity and consistently observed greater risk for T2DM in obese, non-Caucasian youth. In the current review we describe recent advances in understanding how obesity and metabolic status in children and adolescents confers various risk profiles for T2DM among Latinos, African-Americans, Caucasians, Asians and Native Americans. These possible determinants include ectopic fat distribution, adipose tissue inflammation and fibrosis, and elevated plasma levels of non-esterified free fatty acids. Future work should aim to elucidate the ethnic-specific pathophysiology of T2DM in order to develop and implement appropriate prevention and treatment strategies based on different ethnic profiles of diabetes risk. PMID:24445905

  14. Mechanism underlying defective interferon gamma-induced IDO expression in non-obese diabetic mouse fibroblasts.

    PubMed

    Hosseini-Tabatabaei, Azadeh; Jalili, Reza Baradar; Li, Yunyuan; Kilani, Ruhangiz T; Moeen Rezakhanlou, Alireza; Ghahary, Aziz

    2012-01-01

    Indoleamine 2,3-dioxygenase (IDO) can locally suppress T cell-mediated immune responses. It has been shown that defective self-tolerance in early prediabetic female non-obese diabetic (NOD) mice can be attributed to the impaired interferon-gamma (IFN-γ)- induced IDO expression in dendritic cells of these animals. As IFN-γ can induce IDO in both dendritic cells and fibroblasts, we asked the question of whether there exists a similar defect in IFN-γ-induced IDO expression in NOD mice dermal fibroblasts. To this end, we examined the effect of IFN-γ on expression of IDO and its enzymatic activity in NOD dermal fibroblasts. The results showed that fibroblasts from either prediabetic (8 wks of age) female or male, and diabetic female or male (12 and 24 wks of age respectively) NOD mice failed to express IDO in response to IFN-γ treatment. To find underlying mechanisms, we scrutinized the IFN- γ signaling pathway and investigated expression of other IFN-γ-modulated factors including major histocompatibility complex class I (MHC-I) and type I collagen (COL-I). The findings revealed a defect of signal transducer and activator of transcription 1 (STAT1) phosphorylation in NOD cells relative to that of controls. Furthermore, we found an increase in MHC-I and suppression of COL-I expression in fibroblasts from both NOD and control mice following IFN-γ treatment; indicating that the impaired response to IFN-γ in NOD fibroblasts is specific to IDO gene. Finally, we showed that an IFN-γ-independent IDO expression pathway i.e. lipopolysaccharide (LPS)-mediated-c-Jun kinase is operative in NOD mice fibroblast. In conclusion, the findings of this study for the first time indicate that IFN-γ fails to induce IDO expression in NOD dermal fibroblasts; this may partially be due to defective STAT1 phosphorylation in IFN-γ-induced-IDO signaling pathway.

  15. Ceramide metabolism is affected by obesity and diabetes in human adipose tissue.

    PubMed

    Błachnio-Zabielska, A U; Pułka, M; Baranowski, M; Nikołajuk, A; Zabielski, P; Górska, M; Górski, J

    2012-02-01

    Ceramide is involved in development of insulin resistance. However, there are no data on ceramide metabolism in human adipose tissue. The aim of our study was to examine sphingolipid metabolism in fat tissue from obese nondiabetic (n = 11), obese diabetic (n = 11), and lean nondiabetic (n = 8) subjects. The content of ceramide (Cer), dihydroceramide (dhCer), sphingosine (SPH), sphinganine (SPA), sphingosine-1-phosphate (S1P; pmol/mg of protein), the expression (mRNA) and activity of key enzymes responsible for Cer metabolism: serine palmitoyltransferase (SPT), neutral and acidic sphingomyelinase (nSMase and aSMase, respectively), and neutral and acidic ceramidase (nCDase and aCDase, respectively) were examined in human adipose tissue. The contents of SPA and Cer were significantly lower whereas the content of dhCer was higher in both obese groups than the respective values in the lean subjects. The expression of examined enzymes was elevated in both obese groups. The SPT and CDases activity increased whereas aSMase activity deceased in both obese groups. We have found correlation between adipose tissue Cer content and plasma adiponectin concentration (r = 0.69, P < 0.001) and negative correlation between total Cer content and HOMA-IR index (homeostasis model of insulin resistance) (r = -0.67, P < 0.001). We have found that both obesity and diabetes affected pathways of sphingolipid metabolism in the adipose tissue.

  16. Estimation of risk for diabetes according to the metabolically healthy status stratified by degree of obesity in Korean men.

    PubMed

    Ryoo, Jae-Hong; Park, Sung Keun; Ye, Sungmin; Choi, Joong-Myung; Oh, Chang-Mo; Kim, Sun Yong; Shin, Ju-Young; Park, Jai Hyung; Hong, Hyun Pyo; Ko, Taeg Su

    2015-12-01

    Although obesity is clearly identified as a risk factor for diabetes, the relationship between diabetes and metabolically healthy status of obesity is less clear. This study was aimed to evaluate the incidental risk of diabetes according to metabolically healthy status of obesity. 31,834 Korean men without diabetes categorized into six groups according to their metabolically healthy status stratified by degree of obesity were followed up for 5 years: metabolically healthy normal weight (MH-NW), metabolically healthy overweight (MH-OW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MU-NW), metabolically unhealthy overweight (MU-OW), and metabolically unhealthy obese (MUO). Cox proportional hazards analysis was used to measure the risk for diabetes according to their categories. While overall incidence was 9.0 %, incidence of diabetes was in proportion to the degree of obesity and metabolically healthy status (MH-NW: 6.3 %, MH-OW: 7.5 %, MHO: 9.2 %, MU-NW: 11.8 %, MU-OW: 14.9 %, MUO: 20.1 %). When MH-NW was set as reference, the adjusted HRs (95 % CI) for diabetes of the MH-OW, MHO, MU-NW, MU-OW, MUO compared to MH-NW were 1.18 (1.06-1.32), 1.58 (1.03-2.41), 1.81 (1.61-2.04), 2.36 (2.11-2.63), and 3.47 (2.84-4.24), respectively. In conclusion, risk for diabetes was in proportion to the degree of obesity in both metabolically healthy and unhealthy group. Metabolically healthy status was more significant determinant for incident diabetes than obesity itself.

  17. Obesity, diabetes, and leptin resistance promote tau pathology in a mouse model of disease.

    PubMed

    Platt, T L; Beckett, T L; Kohler, K; Niedowicz, D M; Murphy, M P

    2016-02-19

    Obesity and type 2 diabetes mellitus (T2DM) convey an increased risk for developing dementia. The microtubule-associated protein tau is implicated in neurodegenerative disease by undergoing hyperphosphorylation and aggregation, leading to cytotoxicity and neurodegeneration. Enzymes involved in the regulation of tau phosphorylation, such as GSK3β, are tightly associated with pathways found to be dysregulated in T2DM. We have shown previously that leptin-resistant mice, which develop obesity and a diabetic phenotype, display elevated levels of tau phosphorylation. Here we show cells cultured with leptin, an adipokine shown to have neuroprotective effects, reduces tau phosphorylation. To explore how this mechanism works in vivo we transduced an existing diabetic mouse line (Lepr(db/db)) with a tau mutant (tau(P301L)) via adeno-associated virus (AAV). The resulting phenotype included a striking increase in tau phosphorylation and the number of neurofibrillary tangles (NFTs) found within the hippocampus. We conclude that leptin resistance-induced obesity and diabetes accelerates the development of tau pathology. This model of metabolic dysfunction and tauopathy provides a new system in which to explore the mechanisms underlying the ways in which leptin resistance and diabetes influence development of tau pathology, and may ultimately be related to the development of NFTs.

  18. Characterization of hearing loss in aged type II diabetics.

    PubMed

    Frisina, Susan T; Mapes, Frances; Kim, SungHee; Frisina, D Robert; Frisina, Robert D

    2006-01-01

    Presbycusis - age-related hearing loss - is the number one communicative disorder and a significant chronic medical condition of the aged. Little is known about how type II diabetes, another prevalent age-related medical condition, and presbycusis interact. The present investigation aimed to comprehensively characterize the nature of hearing impairment in aged type II diabetics. Hearing tests measuring both peripheral (cochlea) and central (brainstem and cortex) auditory processing were utilized. The majority of differences between the hearing abilities of the aged diabetics and their age-matched controls were found in measures of inner ear function. For example, large differences were found in pure-tone audiograms, wideband noise and speech reception thresholds, and otoacoustic emissions. The greatest deficits tended to be at low frequencies. In addition, there was a strong tendency for diabetes to affect the right ear more than the left. One possible interpretation is that as one develops presbycusis, the right ear advantage is lost, and this decline is accelerated by diabetes. In contrast, auditory processing tests that measure both peripheral and central processing showed fewer declines between the elderly diabetics and the control group. Consequences of elevated blood sugar levels as possible underlying physiological mechanisms for the hearing loss are discussed.

  19. Virtual Reality Technologies for Research and Education in Obesity and Diabetes: Research Needs and Opportunities

    PubMed Central

    Ershow, Abby G; Peterson, Charles M; Riley, William T; Rizzo, Albert “Skip”; Wansink, Brian

    2011-01-01

    The rising rates, high prevalence, and adverse consequences of obesity and diabetes call for new approaches to the complex behaviors needed to prevent and manage these conditions. Virtual reality (VR) technologies, which provide controllable, multisensory, interactive three-dimensional (3D) stimulus environments, are a potentially valuable means of engaging patients in interventions that foster more healthful eating and physical activity patterns. Furthermore, the capacity of VR technologies to motivate, record, and measure human performance represents a novel and useful modality for conducting research. This article summarizes background information and discussions for a joint July 2010 National Institutes of Health – Department of Defense workshop entitled Virtual Reality Technologies for Research and Education in Obesity and Diabetes. The workshop explored the research potential of VR technologies as tools for behavioral and neuroscience studies in diabetes and obesity, and the practical potential of VR in fostering more effective utilization of diabetes- and obesity-related nutrition and lifestyle information. Virtual reality technologies were considered especially relevant for fostering desirable health-related behaviors through motivational reinforcement, personalized teaching approaches, and social networking. Virtual reality might also be a means of extending the availability and capacity of health care providers. Progress in the field will be enhanced by further developing available platforms and taking advantage of VR’s capabilities as a research tool for well-designed hypothesis-testing behavioral science. Multidisciplinary collaborations are needed between the technology industry and academia, and among researchers in biomedical, behavioral, pedagogical, and computer science disciplines. Research priorities and funding opportunities for use of VR to improve prevention and management of obesity and diabetes can be found at agency websites (National

  20. Virtual reality technologies for research and education in obesity and diabetes: research needs and opportunities.

    PubMed

    Ershow, Abby G; Peterson, Charles M; Riley, William T; Rizzo, Albert Skip; Wansink, Brian

    2011-03-01

    The rising rates, high prevalence, and adverse consequences of obesity and diabetes call for new approaches to the complex behaviors needed to prevent and manage these conditions. Virtual reality (VR) technologies, which provide controllable, multisensory, interactive three-dimensional (3D) stimulus environments, are a potentially valuable means of engaging patients in interventions that foster more healthful eating and physical activity patterns. Furthermore, the capacity of VR technologies to motivate, record, and measure human performance represents a novel and useful modality for conducting research. This article summarizes background information and discussions for a joint July 2010 National Institutes of Health - Department of Defense workshop entitled Virtual Reality Technologies for Research and Education in Obesity and Diabetes. The workshop explored the research potential of VR technologies as tools for behavioral and neuroscience studies in diabetes and obesity, and the practical potential of VR in fostering more effective utilization of diabetes- and obesity-related nutrition and lifestyle information. Virtual reality technologies were considered especially relevant for fostering desirable health-related behaviors through motivational reinforcement, personalized teaching approaches, and social networking. Virtual reality might also be a means of extending the availability and capacity of health care providers. Progress in the field will be enhanced by further developing available platforms and taking advantage of VR's capabilities as a research tool for well-designed hypothesis-testing behavioral science. Multidisciplinary collaborations are needed between the technology industry and academia, and among researchers in biomedical, behavioral, pedagogical, and computer science disciplines. Research priorities and funding opportunities for use of VR to improve prevention and management of obesity and diabetes can be found at agency websites (National

  1. Virtual reality technologies for research and education in obesity and diabetes: research needs and opportunities.

    PubMed

    Ershow, Abby G; Peterson, Charles M; Riley, William T; Rizzo, Albert Skip; Wansink, Brian

    2011-03-01

    The rising rates, high prevalence, and adverse consequences of obesity and diabetes call for new approaches to the complex behaviors needed to prevent and manage these conditions. Virtual reality (VR) technologies, which provide controllable, multisensory, interactive three-dimensional (3D) stimulus environments, are a potentially valuable means of engaging patients in interventions that foster more healthful eating and physical activity patterns. Furthermore, the capacity of VR technologies to motivate, record, and measure human performance represents a novel and useful modality for conducting research. This article summarizes background information and discussions for a joint July 2010 National Institutes of Health - Department of Defense workshop entitled Virtual Reality Technologies for Research and Education in Obesity and Diabetes. The workshop explored the research potential of VR technologies as tools for behavioral and neuroscience studies in diabetes and obesity, and the practical potential of VR in fostering more effective utilization of diabetes- and obesity-related nutrition and lifestyle information. Virtual reality technologies were considered especially relevant for fostering desirable health-related behaviors through motivational reinforcement, personalized teaching approaches, and social networking. Virtual reality might also be a means of extending the availability and capacity of health care providers. Progress in the field will be enhanced by further developing available platforms and taking advantage of VR's capabilities as a research tool for well-designed hypothesis-testing behavioral science. Multidisciplinary collaborations are needed between the technology industry and academia, and among researchers in biomedical, behavioral, pedagogical, and computer science disciplines. Research priorities and funding opportunities for use of VR to improve prevention and management of obesity and diabetes can be found at agency websites (National

  2. Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes.

    PubMed

    Scheen, André J; Van Gaal, Luc F

    2014-11-01

    The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent inflammation, abnormal hormone secretion, and various metabolic disturbances that contribute to insulin resistance and insulin secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that leads to cardiovascular disease, liver pathologies, and cancer. Despite the importance of weight control strategies in the prevention and management of type 2 diabetes, long-term results from lifestyle or drug interventions are generally disappointing. Furthermore, most of the classic glucose-lowering drugs have a side-effect of weight gain, which renders the management of most overweight or obese people with type 2 diabetes even more challenging. Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns. The gastrointestinal lipase inhibitor orlistat was the only anti-obesity drug available until the recent US, but not European, launch of phentermine-controlled-release topiramate and lorcaserin. Improved knowledge about bodyweight regulation opens new prospects for the potential use of peptides derived from the gut or the adipose tissue. Combination therapy will probably be necessary to avoid compensatory mechanisms and potentiate initial weight loss while avoiding weight regain. New glucose-lowering treatments, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic drugs by promoting weight loss while improving glucose control. In this Review, we explore the overlapping pathophysiology and also how various treatments can, alone or in combination, combat the dual burden of obesity and type 2 diabetes.

  3. [Endocrine disruptors: A missing link in the pandemy of type 2 diabetes and obesity?].

    PubMed

    Chevalier, Nicolas; Fénichel, Patrick

    2016-01-01

    The prevalence of metabolic syndrome, obesity and type 2 diabetes has dramatically increased worldwide during the last few decades and exceeds World Health Organisation's predictions. Lifestyle factors such as decreased physical activity and energy dense diet, together with a genetic predisposition, are well-known actors in the pathophysiology of these metabolic diseases. However, there is accumulating evidence suggesting that the increased presence of endocrine disrupting chemicals (EDCs) in the environment, may also explain an important part in the incidence of metabolic syndrome, obesity and type 2 diabetes. EDCs are found in everyday products (including food, plastic bottles, metal cans, toys, cosmetics, pesticides…) and used in the manufacture of food. They interfere with the synthesis, secretion, transport, activity and/or elimination of natural hormones. Those interferences can block or mimic hormone actions and thus induce a wide range of adverse effects (especially reproductive effects and hormone-dependent cancers). In rodents, acute exposure to bisphenol A is responsible for modifications of insulin synthesis and secretion in pancreatic beta cells but also for modifications of insulin signalling in liver, skeletal muscle and adipose tissue, which both lead to insulin-resistance, a major condition in pathophysiology of metabolic syndrome, obesity and type 2 diabetes. In humans, some epidemiologic reports suggested a strong link between exposure to some persistant EDCs (as organochlorine pesticides, dioxins and polychlorinated biphenyl ethers) and type 2 diabetes and obesity, especially after acute and accidental releases of EDCs (Seveso plant explosion, Vietnam war veterans). Other cross-sectional studies among the world reported suggestive to strong association between diabetes and obesity and EDCs exposure, especially for persistant organic pollutants, which should now be considered as insulin-resistance risk factors. PMID:26655260

  4. Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes.

    PubMed

    Scheen, André J; Van Gaal, Luc F

    2014-11-01

    The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent inflammation, abnormal hormone secretion, and various metabolic disturbances that contribute to insulin resistance and insulin secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that leads to cardiovascular disease, liver pathologies, and cancer. Despite the importance of weight control strategies in the prevention and management of type 2 diabetes, long-term results from lifestyle or drug interventions are generally disappointing. Furthermore, most of the classic glucose-lowering drugs have a side-effect of weight gain, which renders the management of most overweight or obese people with type 2 diabetes even more challenging. Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns. The gastrointestinal lipase inhibitor orlistat was the only anti-obesity drug available until the recent US, but not European, launch of phentermine-controlled-release topiramate and lorcaserin. Improved knowledge about bodyweight regulation opens new prospects for the potential use of peptides derived from the gut or the adipose tissue. Combination therapy will probably be necessary to avoid compensatory mechanisms and potentiate initial weight loss while avoiding weight regain. New glucose-lowering treatments, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic drugs by promoting weight loss while improving glucose control. In this Review, we explore the overlapping pathophysiology and also how various treatments can, alone or in combination, combat the dual burden of obesity and type 2 diabetes. PMID:24731666

  5. Diabetes, sleep apnea, obesity and cardiovascular disease: Why not address them together?

    PubMed

    Surani, Salim R

    2014-06-15

    Obesity, sleep apnea, diabetes and cardiovascular diseases are some of the most common diseases encountered by the worldwide population, with high social and economic burdens. Significant emphasis has been placed on obtaining blood pressure, body mass index, and placing importance on screening for signs and symptoms pointing towards cardiovascular disease. Symptoms related to sleep, or screening for sleep apnea has been overlooked by cardiac, diabetic, pulmonary and general medicine clinics despite recommendations for screening by several societies. In recent years, there is mounting data where obesity and obstructive sleep apnea sit at the epicenter and its control can lead to improvement and prevention of diabetes and cardiovascular complications. This editorial raises questions as to why obstructive sleep apnea screening should be included as yet another vital sign during patient initial inpatient or outpatient visit. PMID:24936259

  6. Effects of Age, Sex, and Obesity on the Single-Dose Pharmacokinetics of Omarigliptin in Healthy Subjects.

    PubMed

    Addy, Carol; Tatosian, Daniel A; Glasgow, Xiaoli S; Iii, Isaias Noel Gendrano; Sisk, Christine McCrary; Kauh, Eunkyung A; Stoch, S Aubrey; Wagner, John A

    2016-09-01

    Omarigliptin is being developed as a potent, once-weekly, oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. This double-blind, randomized, placebo-controlled study evaluated the effects of age, sex, and obesity on the pharmacokinetics of omarigliptin in healthy subjects. A single oral dose of omarigliptin 10 mg (n = 6/panel) or placebo (n = 2/panel) was administered in the fasted state to elderly nonobese men and women, young obese (30 ≤ body mass index [BMI] ≤ 35 kg/m(2) ) men and women, and young nonobese women of nonchildbearing potential. Plasma was collected at selected postdose times for evaluation of omarigliptin concentrations. Pharmacokinetic parameters were compared with historical data from a previously-conducted single-dose study in young, healthy, nonobese men. There were no clinically significant differences in omarigliptin AUC0-∞ , the primary pharmacokinetic parameter for assessing efficacy and safety, based on age, sex, or BMI (pooled nonobese elderly versus pooled nonobese young, young nonobese female versus young nonobese male, and pooled young obese versus pooled young nonobese). There were no serious adverse events or hypoglycemic events attributable to omarigliptin administration. Demographic factors and BMI had no meaningful effect on omarigliptin pharmacokinetics, suggesting that dose adjustment based on age, sex, or obesity is not required. PMID:27627193

  7. Expression of CD73 and A2A receptors in cells from subjects with obesity and type 2 diabetes mellitus.

    PubMed

    Guzman-Flores, Juan M; Cortez-Espinosa, Nancy; Cortés-Garcia, Juan D; Vargas-Morales, Juan M; Cataño-Cañizalez, Yolanda G; Rodríguez-Rivera, Jaime G; Portales-Perez, Diana P

    2015-08-01

    Regulatory T cells have various mechanisms to suppress the inflammatory response, among these, the modulation of the microenvironment through adenosine and with the participation of CD39, CD73 and A2A. The aim of this study was to assess the expression of CD73 and A2A in immune cells and the effect of activation of A2A by an adenosine analogue on apoptosis in patients with obesity and type 2 diabetes mellitus (T2D). CD73 and A2A expression were analyzed by flow cytometry in lymphocyte subpopulations from patients with obesity (n = 22), T2D (n = 22), and healthy subjects (n = 20). Lymphocytes were treated with the selective A2A antagonist (ZM241385) or the selective A2A agonist (CGS21680), and apoptotic cells were detected by Annexin V. We found an increased expression of CD39 coupled to a decrease in CD73 in the patient groups with obesity and T2D compared to the control group in the different studied lymphocyte subpopulations. A2A expression was found to be increased in different subpopulations of lymphocytes from T2D patients. We also detected positive correlations between CD39+ cells and age and BMI. Meanwhile, CD73+ cells showed negative correlations with age, WHR, BMI, FPG, HbAc1, triglycerides and cholesterol. Moreover, an increase in the percentage of apoptotic cells from T2D patients with regard to the groups with obesity and control was observed. In addition, the CD8+ T cells of patients with T2D exhibited decreased apoptosis when treated with the A2A agonist. In conclusion, our data suggest a possible role for CD73 and A2A in inflammation observed in patients with T2D and obesity mediated via apoptosis.

  8. Mild type II diabetes markedly increases glucose cycling in the postabsorptive state and during glucose infusion irrespective of obesity.

    PubMed Central

    Efendic, S; Karlander, S; Vranic, M

    1988-01-01

    Glucose cycling (GC; G in equilibrium G6P) equals 14% of glucose production in postabsorptive man. Our aim was to determine glucose cycling in six lean and six overweight mild type II diabetics (fasting glycemia: 139 +/- 10 and 152 +/- 7 mg/dl), in postabsorptive state (PA) and during glucose infusion (2 mg/kg per min). 14 control subjects were weight and age matched. GC is a function of the enzyme that catalyzes the reaction opposite the net flux and is the difference between hepatic total glucose output (HTGO) (2-[3H]glucose) and hepatic glucose production (HGP) (6-[3H]-glucose). Postabsorptively, GC is a function of glucokinase. With glucose infusion the flux is reversed (net glucose uptake), and GC is a function of glucose 6-phosphatase. In PA, GC was increased by 100% in lean (from 0.25 +/- 0.07 to 0.43 +/- .08 mg/kg per min) and obese (from 0.22 +/- 0.05 to 0.50 +/- 0.07) diabetics. HGP and HTGO increased in lean and obese diabetics by 41 and 33%. Glucose infusion suppressed apparent phosphatase activity and gluconeogenesis much less in diabetics than controls, resulting in marked enhancement (400%) in HTGO and HGP, GC remained increased by 100%. Although the absolute responses of C-peptide and insulin were comparable to those of control subjects, they were inappropriate for hyperglycemia. Peripheral insulin resistance relates to decreased metabolic glucose clearance (MCR) and inadequate increase of uptake during glucose infusion. We conclude that increases in HGP and HTGO and a decrease of MCR are characteristic features of mild type II diabetes and are more pronounced during glucose infusion. There is also an increase in hepatic GC, a stopgap that controls changes from glucose production to uptake. Postabsorptively, this limits the increase of HGP and glycemia. In contrast, during glucose infusion, increased GC decreases hepatic glucose uptake and thus contributes to hyperglycemia. Obesity per se did not affect GC. An increase in glucose cycling and

  9. Hepatocyte TRAF3 promotes insulin resistance and type 2 diabetes in mice with obesity

    PubMed Central

    Chen, Zheng; Canet, Mark J.; Sheng, Liang; Jiang, Lin; Xiong, Yi; Yin, Lei; Rui, Liangyou

    2015-01-01

    Objective Metabolic inflammation is believed to promote insulin resistance and type 2 diabetes progression in obesity. TRAF3, a cytoplasmic signaling protein, has been known to mediate/modulate cytokine signaling in immune cells. The goal is to define the metabolic function of hepatic TRAF3 in the setting of obesity. Methods Hepatocyte-specific TRAF3 knockout mice were generated using the loxp/albumin-cre system. Liver TRAF3 was deleted in adult obese mice via Cre adenoviral infection. Both high fat diet-induced and genetic obesity were examined. TRAF3 levels and insulin signaling were measured by immunoblotting. Insulin sensitivity, hepatic glucose production, and glucose metabolism were examined by glucose, insulin, and pyruvate tolerance tests. Hepatic steatosis was examined by Oil red O staining of liver sections and measuring liver triacylglycerol levels. Results Liver TRAF3 levels were lower in the fasted states in normal mice, and were aberrantly higher in obese mice and in mice with streptozotocin-induced hyperglycemia. Glucose directly increased TRAF3 levels in primary hepatocytes. Hepatocyte-specific deletion of TRAF3 decreased hyperinsulinemia, insulin resistance, glucose intolerance, and hepatic steatosis in mice with either high fat diet-induced obesity or genetic obesity (ob/ob); conversely, in lean mice, adenovirus-mediated overexpression of TRAF3 in the liver induced hyperinsulinemia, insulin resistance, and glucose intolerance. Deletion of TRAF3 enhanced the ability of insulin to stimulate phosphorylation of Akt in hepatocytes, whereas overexpression of TRAF3 suppressed insulin signaling. Conclusions Glucose increases the levels of hepatic TRAF3. TRAF3 in turn promotes hyperglycemia through increasing hepatic glucose production, thus forming a glucose-TRAF3 reinforcement loop in the liver. This positive feedback loop may drive the progression of type 2 diabetes and nonalcoholic fatty liver disease in obesity. PMID:26909311

  10. Obesity and systolic blood pressure in young adult men born small for gestational age.

    PubMed

    Laganović, Mario; Lela, Ivana Vuković; Premuzić, Vedran; Karanović, Sandra; Vrdoljak, Ana; Jelaković, Bojan

    2013-09-01

    Individuals born small for gestational age (SGA) are supposed to be at higher risk to develop cardiovascular disorders, and recent report showed that concurrent obesity influences blood pressure (BP) in SGA children. Our aim was to investigate the impact of obesity and birth weight on blood pressure values in young adult men born SGA and controls born after normal pregnancy, Normotensive, non-treated adult men were enrolled (N = 185; mean age 21.29 +/- 0.9 years). Birth parameters were obtained from medical records and SGA was defined as birth weight (BW) under 10th percentile for gestational age and obesity as BMI > 25 kg/m2. According to the presence or absence of obesity and BW the subjects were divided into four groups: (1) non-obese with normal BW (N = 50), (2) non-obese SGA (N = 67), (3) obese with normal BW (N = 40), (4) obese SGA (N = 28). BP was measured using Omron M6 and Spacelab 90207 device following the ESH/ESC guidelines. Systolic BP, 24-hour BP variability and pulse pressure were significantly higher in SGA subjects than in those with normal BW (p < 0.05). The highest 24-hour and daytime systolic BP values as well as 24-hour pulse pressure were found in the subgroup of obese SGA subjects (p < 0.001). Significant differences for the above parameters were observed between obese SGA group and non-obese SGA group (p < 0.05). Obese SGA subjects had higher 24-hour and daytime systolic BP values compared to obese normal BW group. No difference was found in BP between non-obese SGA and non-obese group with normal BW (p > 0.05). In addition to BW and shorter pregnancy duration, obesity concurrently and significantly determines systolic BP in young normotensive men and point to a need for more aggressive implementation of healthy lifestyle as early as possible.

  11. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes.

    PubMed

    Esser, Nathalie; Legrand-Poels, Sylvie; Piette, Jacques; Scheen, André J; Paquot, Nicolas

    2014-08-01

    It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammatory therapies could have a place in prevention and treatment of type 2 diabetes.

  12. Immune Regulators of Inflammation in Obesity-Associated Type 2 Diabetes and Coronary Artery Disease

    PubMed Central

    Strissel, Katherine J.; Denis, Gerald V.; Nikolajczyk, Barbara S.

    2014-01-01

    Purpose To summarize current work identifying inflammatory components that underlie associations between obesity-associated type 2 diabetes (T2D) and coronary artery disease (CAD). Recent findings Recent studies implicate immune cells as drivers of pathogenic inflammation in human T2D. Inflammatory lymphocytes characterize unhealthy adipose tissue (AT), but regional adipose volume, primarily visceral and pericardial fat; also predict severity and risk for obesity-associated CAD. Having a greater understanding of shared characteristics between inflammatory cells from different AT depots and a more accessible tissue such as blood will facilitate progress towards clinical translation of our appreciation of obesity as an inflammatory disease. Summary Obesity predisposes inflammation and metabolic dysfunction through multiple mechanisms, but these mechanisms remain understudied in humans. Studies of obese subjects have identified disproportionate impacts of specific T cell subsets in metabolic diseases like T2D. Based on demonstration that AT inflammation is depot-specific, analysis of adiposity by waist-to-hip ratio or magnetic resonance imaging (MRI) will increase interpretive value of lymphocyte-focused studies and aid clinicians in determining which obese individuals are at highest risk for CAD. New tools to combat obesity-associated CAD and other co-morbidities will stem from identification of immune cell-mediated inflammatory networks that are amenable to pharmacological interventions. PMID:25106001

  13. Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling.

    PubMed

    Pane, Jessica A; Fleming, Fiona E; Graham, Kate L; Thomas, Helen E; Kay, Thomas W H; Coulson, Barbara S

    2016-07-13

    Rotavirus infection is associated with childhood progression to type 1 diabetes. Infection by monkey rotavirus RRV accelerates diabetes onset in non-obese diabetic (NOD) mice, which relates to regional lymph node infection and a T helper 1-specific immune response. When stimulated ex vivo with RRV, plasmacytoid dendritic cells (pDCs) from naïve NOD mice secrete type I interferon, which induces the activation of bystander lymphocytes, including islet-autoreactive T cells. This is our proposed mechanism for diabetes acceleration by rotaviruses. Here we demonstrate bystander lymphocyte activation in RRV-infected NOD mice, which showed pDC activation and strong upregulation of interferon-dependent gene expression, particularly within lymph nodes. The requirement for type I interferon signalling was analysed using NOD mice lacking a functional type I interferon receptor (NOD.IFNAR1(-/-) mice). Compared with NOD mice, NOD.IFNAR1(-/-) mice showed 8-fold higher RRV titers in lymph nodes and 3-fold higher titers of total RRV antibody in serum. However, RRV-infected NOD.IFNAR1(-/-) mice exhibited delayed pDC and lymphocyte activation, no T helper 1 bias in RRV-specific antibodies and unaltered diabetes onset when compared with uninfected controls. Thus, the type I interferon signalling induced by RRV infection is required for bystander lymphocyte activation and accelerated type 1 diabetes onset in genetically susceptible mice.

  14. Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling

    PubMed Central

    Pane, Jessica A.; Fleming, Fiona E.; Graham, Kate L.; Thomas, Helen E.; Kay, Thomas W. H.; Coulson, Barbara S.

    2016-01-01

    Rotavirus infection is associated with childhood progression to type 1 diabetes. Infection by monkey rotavirus RRV accelerates diabetes onset in non-obese diabetic (NOD) mice, which relates to regional lymph node infection and a T helper 1-specific immune response. When stimulated ex vivo with RRV, plasmacytoid dendritic cells (pDCs) from naïve NOD mice secrete type I interferon, which induces the activation of bystander lymphocytes, including islet-autoreactive T cells. This is our proposed mechanism for diabetes acceleration by rotaviruses. Here we demonstrate bystander lymphocyte activation in RRV-infected NOD mice, which showed pDC activation and strong upregulation of interferon-dependent gene expression, particularly within lymph nodes. The requirement for type I interferon signalling was analysed using NOD mice lacking a functional type I interferon receptor (NOD.IFNAR1−/− mice). Compared with NOD mice, NOD.IFNAR1−/− mice showed 8-fold higher RRV titers in lymph nodes and 3-fold higher titers of total RRV antibody in serum. However, RRV-infected NOD.IFNAR1−/− mice exhibited delayed pDC and lymphocyte activation, no T helper 1 bias in RRV-specific antibodies and unaltered diabetes onset when compared with uninfected controls. Thus, the type I interferon signalling induced by RRV infection is required for bystander lymphocyte activation and accelerated type 1 diabetes onset in genetically susceptible mice. PMID:27405244

  15. Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling.

    PubMed

    Pane, Jessica A; Fleming, Fiona E; Graham, Kate L; Thomas, Helen E; Kay, Thomas W H; Coulson, Barbara S

    2016-01-01

    Rotavirus infection is associated with childhood progression to type 1 diabetes. Infection by monkey rotavirus RRV accelerates diabetes onset in non-obese diabetic (NOD) mice, which relates to regional lymph node infection and a T helper 1-specific immune response. When stimulated ex vivo with RRV, plasmacytoid dendritic cells (pDCs) from naïve NOD mice secrete type I interferon, which induces the activation of bystander lymphocytes, including islet-autoreactive T cells. This is our proposed mechanism for diabetes acceleration by rotaviruses. Here we demonstrate bystander lymphocyte activation in RRV-infected NOD mice, which showed pDC activation and strong upregulation of interferon-dependent gene expression, particularly within lymph nodes. The requirement for type I interferon signalling was analysed using NOD mice lacking a functional type I interferon receptor (NOD.IFNAR1(-/-) mice). Compared with NOD mice, NOD.IFNAR1(-/-) mice showed 8-fold higher RRV titers in lymph nodes and 3-fold higher titers of total RRV antibody in serum. However, RRV-infected NOD.IFNAR1(-/-) mice exhibited delayed pDC and lymphocyte activation, no T helper 1 bias in RRV-specific antibodies and unaltered diabetes onset when compared with uninfected controls. Thus, the type I interferon signalling induced by RRV infection is required for bystander lymphocyte activation and accelerated type 1 diabetes onset in genetically susceptible mice. PMID:27405244

  16. Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes.

    PubMed

    Masuzaki, H; Ogawa, Y; Aizawa-Abe, M; Hosoda, K; Suga, J; Ebihara, K; Satoh, N; Iwai, H; Inoue, G; Nishimura, H; Yoshimasa, Y; Nakao, K

    1999-08-01

    Leptin acts as an adipocyte-derived blood-borne satiety factor that can increase glucose metabolism. To elucidate the therapeutic implications of leptin for obesity-associated diabetes, we crossed transgenic skinny mice overexpressing leptin (Tg/+), which we have developed recently, and lethal yellow KKAy mice (Ay/+), a genetic model for obesity-diabetes syndrome, and examined the metabolic phenotypes of F1 animals. At 6 weeks of age, plasma leptin concentrations in Tg/+ mice with the Ay allele (Tg/+:Ay/+) were significantly higher than those in Ay/+ mice. Although no significant differences in body weight were noted among Tg/+:Ay/+ mice, Ay/+ mice, and their wild-type lean littermates (+/+), glucose and insulin tolerance tests revealed increased glucose tolerance and insulin sensitivity in Tg/+:Ay/+ compared with Ay/+ mice. However, at 12 weeks of age, when plasma leptin concentrations in Ay/+ mice were comparable to those in Tg/+:Ay/+ mice, Tg/+:Ay/+ mice developed obesity-diabetes syndrome similar to that of Ay/+ mice. Body weights of 12-week-old Tg/+:Ay/+ and Ay/+ mice were reduced to those of +/+ mice by a 3-week food restriction; when plasma leptin concentrations remained high in Tg/+:Ay/+ mice but were markedly reduced in Ay/+ and +/+ mice, glucose tolerance and insulin sensitivity in Tg/+:Ay/+ mice were markedly improved as compared with Ay/+ and +/+ mice. The present study demonstrates that hyperleptinemia can delay the onset of impaired glucose metabolism and accelerate the recovery from diabetes during caloric restriction in Tg/+:Ay/+ mice, thereby suggesting the potential usefulness of leptin in combination with a long-term caloric restriction for the treatment of obesity-associated diabetes.

  17. Comparison of Age of Onset and Frequency of Diabetic Complications in the Very Elderly Patients with Type 2 Diabetes

    PubMed Central

    2016-01-01

    Background The prevalence of type 2 diabetes in elderly people has increased dramatically in the last few decades. This study was designed to clarify the clinical characteristics of type 2 diabetes in patients aged ≥80 years according to age of onset. Methods We reviewed the medical records of 289 patients aged ≥80 years with type 2 diabetes at the outpatient diabetes clinics of Kangwon National University Hospital from September 2010 to June 2014. We divided the patients into middle-age-onset diabetes (onset before 65 years of age) and elderly-onset diabetes (onset at 65+ years of age). Results There were 141 male and 148 female patients. The patients had a mean age of 83.2±2.9 years and the mean duration of diabetes was 14.3±10.4 years. One hundred and ninety-nine patients had elderly-onset diabetes. The patients with elderly-onset diabetes had a significantly lower frequency of diabetic retinopathy and nephropathy, lower serum creatinine levels, lower glycated hemoglobin (HbA1c) levels, and similar coronary revascularization and cerebral infarction rates compared to those with middle-age-onset diabetes. There was no frequency difference in coronary revascularization and cerebral infarction and HbA1c levels between three subgroups (<5, 5 to 15, and ≥15 years) of diabetes duration in elderly onset diabetes. However, both in the elderly onset diabetes and middle-age-onset diabetes, the cumulative incidence of retinopathy was increasing rapidly according to the duration of diabetes. Conclusion We report that individuals with elderly-onset diabetes have a lower frequency of diabetic retinopathy and nephropathy and similar cardiovascular complications compared to those with middle-age-onset diabetes. PMID:27586451

  18. Virtual reality and interactive gaming technology for obese and diabetic children: is military medical technology applicable?

    PubMed

    Talbot, Thomas Brett

    2011-03-01

    The Telemedicine and Advanced Technology Research Center has pursued a number of technologies that may have application to the problems of obesity and diabetes management in children. Children are getting fatter because of increased caloric intake and less physical activity. Furthermore, technology advances have failed to significantly improve metabolic control of type 1 diabetes. Behavioral strategies should target video games, mobile phones, and other popular items used by children and seen by them as necessities. Exergaming is considerably more active than traditional video gaming and can be equivalent to moderate-intensity exercise. Diabetes equipment such as continuous glucose monitors and insulin pumps lack integration and live connectivity and suffer from a poor user interface. In contrast, mobile phones offer wireless connectivity, an excellent voice-enabled interface, and cloud connectivity that could possibly serve as a motivational and compliance tool for diabetes patients through text messaging to the patient, parents, and physician. Mobile phones have the potential to motivate and educate obese children as well. Exergaming for obese children could also be integrated into award systems of game consoles and game play time. The key to successful implementation of these strategies depends on the ability to integrate and connect the various technologies.

  19. Neuroadrenergic dysfunction along the diabetes continuum: a comparative study in obese metabolic syndrome subjects.

    PubMed

    Straznicky, Nora E; Grima, Mariee T; Sari, Carolina I; Eikelis, Nina; Lambert, Elisabeth A; Nestel, Paul J; Esler, Murray D; Dixon, John B; Chopra, Reena; Tilbrook, Alan J; Schlaich, Markus P; Lambert, Gavin W

    2012-10-01

    Neuroadrenergic function in type 2 diabetic (T2D) patients without neuropathy is poorly characterized. We therefore compared sympathetic nervous system activity at rest and during an oral glucose tolerance test in obese metabolic syndrome (MetS) subjects classified as glucose intolerant (impaired glucose tolerance [IGT]; n = 17) or treatment-naive T2D (n = 17). Untreated subjects, matched for age (mean 59 ± 1 year), sex, BMI (32.4 ± 0.6 kg/m(2)), and family history of diabetes were studied. We measured resting muscle sympathetic nerve activity (MSNA) by microneurography, whole-body norepinephrine kinetics by isotope dilution, insulin sensitivity by euglycemic-hyperinsulinemic clamp (steady-state glucose utilization adjusted for fat-free mass and steady-state insulin concentration [M/I]), and MetS components. T2D subjects had higher resting MSNA burst incidence (67 ± 4 versus 55 ± 3 bursts per 100 heartbeats; P = 0.05) and arterial norepinephrine levels (264 ± 33 versus 167 ± 16 pg/mL; P = 0.02), lower plasma norepinephrine clearance (by 17%; P = 0.03), and reduced neuronal reuptake compared with IGT subjects (by 46%; P = 0.04). Moreover, norepinephrine spillover responses to glucose ingestion were blunted in T2D subjects. The M/I value independently predicted whole-body norepinephrine spillover (r = -0.47; P = 0.008), whereas fasting insulin level related to neuronal norepinephrine reuptake (r = -0.35, P = 0.047). These findings demonstrate that progression to T2D is associated with increased central sympathetic drive, blunted sympathetic responsiveness, and altered norepinephrine disposition.

  20. Effects of various gastrointestinal procedures on β-cell function in obesity and type 2 diabetes.

    PubMed

    Malin, Steven K; Kashyap, Sangeeta R

    2016-07-01

    Bariatric surgery is a gastrointestinal procedure that has emerged as the most effective treatment for weight loss. Roux-en-Y gastric bypass and sleeve gastrectomy are the main procedures currently performed. However, the benefits of bariatric surgery extend beyond weight loss. In fact, improvements in β-cell function occur before clinically meaningful weight loss and contribute to type 2 diabetes mellitus (T2D) remission. Herein, we discuss evidence supporting the efficacy of bariatric surgery for weight loss and improved insulin secretion in patients with and without T2D. The exact mechanism by which bariatric surgery elicits a favorable change in β-cell function remains unclear, but a leading hypothesis is that rerouted nutrient flow to the gut alters enteroendocrine hormone production (e.g., glucagon-like polypeptide 1, polypeptide tyrosine-tyrosine, ghrelin), gut microbiome metabolites (e.g., lipopolysaccharides, short-chain fatty acids), and circulating bile acid changes that favor appetite suppression, metabolic rate, and insulin action. We also highlight the role of adipose-derived factors (e.g., pancreatic fat content, adiponectin) that may have an effect on β-cell function, as well as discuss the clinical determinants of diabetes remission (e.g., age and T2D duration). Taken together, the acute improvements seen with bariatric surgery are weight-independent and likely related to incretin-mediated effects on postprandial glucose metabolism and insulin sensitivity. Over longer periods of time, increases in bile acids, reductions in pancreatic lipid content, and elevated adiponectin levels may also contribute to reduced disease risk. As a result, the gut appears to be a novel target for favorably preventing and treating obesity-related metabolic disorders. PMID:27568472

  1. Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals

    PubMed Central

    Hatziagelaki, Erifili; Ketterer, Caroline; Heni, Martin; Machicao, Fausto; Stefan, Norbert; Staiger, Harald; Häring, Hans-Ulrich; Fritsche, Andreas

    2012-01-01

    Introduction Single nucleotide polymorphisms (SNPs) in approximately 40 genes have been associated with an increased risk for type 2 diabetes (T2D) in genome-wide association studies. It is not known whether a similar genetic impact on the risk of prediabetes (impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) exists. Methods In our cohort of 1442 non-diabetic subjects of European origin (normal glucose tolerance [NGT] n = 1046, isolated IFG n = 142, isolated IGT n = 140, IFG+IGT n = 114), an impact on glucose homeostasis has been shown for 9 SNPs in previous studies in this specific cohort. We analyzed these SNPs (within or in the vicinity of the genes TCF7L2, KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association with prediabetes. Results The genetic risk load was significantly associated with the risk for IGT (p = 0.0006) in a model including gender, age, BMI and insulin sensitivity. To further evaluate potential confounding effects, we stratified the population on gender, BMI and insulin sensitivity. The association of the risk score with IGT was present in female participants (p = 0.008), but not in male participants. The risk score was significantly associated with IGT (p = 0.008) in subjects with a body mass index higher than 30 kg/m2 but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association between the genetic load and the risk for IGT (p = 0.01) was found. Discussion We found that T2D genetic risk alleles cause an increased risk for IGT. This effect was not present in male, lean and insulin sensitive subjects, suggesting a protective role of beneficial environmental factors on the genetic risk. PMID:22768041

  2. Obesity and type 2 diabetes in Northern Canada's remote First Nations communities: the dietary dilemma.

    PubMed

    Haman, F; Fontaine-Bisson, B; Batal, M; Imbeault, P; Blais, J M; Robidoux, M A

    2010-12-01

    First Nations populations in Northwestern Ontario have undergone profound dietary and lifestyle transformations in less than 50 years, which have contributed to the alarming rise in obesity and obesity-related diseases, in particular type 2 diabetes mellitus. Even though the genetic background of First Nations peoples differs from that of the Caucasians, genetics alone cannot explain such a high prevalence in obesity and type 2 diabetes. Modifications in lifestyle and diet are major contributors for the high prevalence of chronic diseases. What remains constant in the literature is the persistent view that locally harvested and prepared foods are of tremendous value to First Nations peoples providing important health and cultural benefits that are increasingly being undermined by western-based food habits. However, the complexities of maintaining a traditional diet require a multifaceted approach, which acknowledges the relationship between benefits, risks and viability that cannot be achieved using purely conventional medical and biological approaches. This brief review explores the biological predispositions and potential environmental factors that contribute to the development of the high incidence of obesity and obesity-related diseases in First Nations communities in Northern Canada. It also highlights some of the complexities of establishing exact physiological causes and providing effective solutions.

  3. The Gut Microbiota Modulates Glycaemic Control and Serum Metabolite Profiles in Non-Obese Diabetic Mice

    PubMed Central

    Greiner, Thomas U.; Hyötyläinen, Tuulia; Knip, Mikael; Bäckhed, Fredrik; Orešič, Matej

    2014-01-01

    Islet autoimmunity in children who later progress to type 1 diabetes is preceded by dysregulated serum metabolite profiles, but the origin of these metabolic changes is unknown. The gut microbiota affects host metabolism and changes in its composition contribute to several immune-mediated diseases; however, it is not known whether the gut microbiota is involved in the early metabolic disturbances in progression to type 1 diabetes. We rederived non-obese diabetic (NOD) mice as germ free to explore the potential role of the gut microbiota in the development of diabetic autoimmunity and to directly investigate whether the metabolic profiles associated with the development of type 1 diabetes can be modulated by the gut microbiota. The absence of a gut microbiota in NOD mice did not affect the overall diabetes incidence but resulted in increased insulitis and levels of interferon gamma and interleukin 12; these changes were counterbalanced by improved peripheral glucose metabolism. Furthermore, we observed a markedly increased variation in blood glucose levels in the absence of a microbiota in NOD mice that did not progress to diabetes. Additionally, germ-free NOD mice had a metabolite profile similar to that of pre-diabetic children. Our data suggest that germ-free NOD mice have reduced glycaemic control and dysregulated immunologic and metabolic responses. PMID:25390735

  4. Dietary Patterns and Relationship to Obesity-Related Health Outcomes and Mortality in Adults 75 Years of Age or Greater

    PubMed Central

    Hsiao, P.Y.; Mitchell, D.C.; Coffman, D.L.; Wood, G. Craig; Hartman, T.J.; Still, C.; Jensen, G.L.

    2015-01-01

    Background The prevalence of obesity-related adverse health outcomes is increasing among older adults. Because it is thought that nutrition plays an important role in successful aging, there has been considerable interest in the association between dietary patterns of older adults and obesity-related health outcomes. Objective This study examined the association between dietary patterns and mortality and prevalence of obesity-related health outcomes, namely cardiovascular disease (CVD), type 2 diabetes mellitus, hypertension, and metabolic syndrome (MetSyn), over a 5-year follow-up period in adults aged 75 years or greater. Design A longitudinal observational study with cross-sectional dietary assessment. Setting Rural Central Pennsylvania. Participants Community-dwelling older adults (N = 449; 76.5 years old; 57% female). Measurements Multiple, unannounced, 24-hour dietary recalls were used to collect dietary intake. Cluster analysis was used to derive dietary patterns. Prevalence of CVD, diabetes mellitus, hypertension, and MetSyn was extracted from outpatient electronic medical records. Logistic regression was used to examine the associations between dietary patterns and health outcomes and mortality. Results ‘Sweets and Dairy’, ‘Health-Conscious’ and ‘Western’ dietary patterns were identified. Compared to the ‘Health-Conscious’ pattern, those in the ‘Sweets and Dairy’ pattern had increased odds of hypertension over the follow-up period; adjusted odds ratio (95% CI) was 2.18 (1.11-4.30). No significant associations were found for CVD, diabetes mellitus, MetSyn or mortality with dietary patterns. Conclusions These findings support the potential value of healthy dietary patterns in the management of hypertension in older adults. We did not observe any other strong associations between dietary patterns and health outcomes or mortality in persons ≥ 75 years of age; thus failing to support the use of overly restrictive diet prescriptions for

  5. Everything in Moderation - Dietary Diversity and Quality, Central Obesity and Risk of Diabetes

    PubMed Central

    de Oliveira Otto, Marcia C.; Padhye, Nikhil S.; Bertoni, Alain G.; Jacobs, David R.; Mozaffarian, Dariush

    2015-01-01

    Diet guidelines recommend increasing dietary diversity. Yet, metrics for dietary diversity have neither been well-defined nor evaluated for impact on metabolic health. Also, whether diversity has effects independent of diet quality is unknown. We characterized and evaluated associations of diet diversity and quality with abdominal obesity and type II diabetes (T2D) in the Multi-Ethnic Study of Atherosclerosis. At baseline (2000–02), diet was assessed among 5,160 Whites, Hispanic, Blacks, and Chinese age 45–84 y and free of T2D, using a validated questionnaire. Three different aspects of diet diversity were characterized including count (number of different food items eaten more than once/week, a broad measure of diversity), evenness (Berry index, a measure of the spread of the diversity), and dissimilarity (Jaccard distance, a measure of the diversity of the attributes of the foods consumed). Diet quality was characterized using aHEI, DASH, and a priori pattern. Count and evenness were weakly positively correlated with diet quality (r with AHEI: 0.20, 0.04), while dissimilarity was moderately inversely correlated (r = -0.34). In multivariate models, neither count nor evenness was associated with change in waist circumference (WC) or incident T2D. Greater food dissimilarity was associated with higher gain in WC (p-trend<0.01), with 120% higher gain in participants in the highest quintile of dissimilarity scores. Diet diversity was not associated with incident T2D. Also, none of the diversity metrics were associated with change in WC or incident T2D when restricted to only healthier or less healthy foods. Higher diet quality was associated with lower risk of T2D. Our findings provide little evidence for benefits of diet diversity for either abdominal obesity or diabetes. Greater dissimilarity among foods was actually associated with gain in WC. These results do not support the notion that “eating everything in moderation” leads to greater diet quality or

  6. Exercise without weight loss is an effective strategy for obesity reduction in obese individuals with and without Type 2 diabetes.

    PubMed

    Lee, SoJung; Kuk, Jennifer L; Davidson, Lance E; Hudson, Robert; Kilpatrick, Katherine; Graham, Terry E; Ross, Robert

    2005-09-01

    It is unclear whether chronic exercise without caloric restriction or weight loss is a useful strategy for obesity reduction in obese men with and without Type 2 diabetes (T2D). We examined the effects of exercise without weight loss on total and regional adiposity and skeletal muscle mass and composition in lean men and in obese men with and without T2D. Twenty-four men participated in 13 wk of supervised aerobic exercise, five times per week for 60 min at a moderate intensity (approximately 60% peak oxygen uptake). Total and regional body composition was measured by magnetic resonance imaging. Skeletal muscle composition was determined using computed tomography. Cardiorespiratory fitness was assessed using a graded maximal treadmill test. Body weight did not change within any group in response to exercise (P > 0.1). Significant reductions in total, abdominal subcutaneous, and visceral fat were observed within each group (P < 0.01). The reduction in total and abdominal subcutaneous fat was not different (P > 0.1) between groups; however, the reduction in visceral fat was greater (P < 0.01) in the obese and T2D groups by comparison to the lean group. A significant (P < 0.01) increase in total skeletal muscle, high-density muscle area, and mean muscle attenuation was observed independent of group, and these changes were not different between groups (P > 0.1). Accordingly, whole body fat-to-muscle ratio was increased (P < 0.01) independent of groups. In conclusion, regular exercise without weight loss is associated with a substantial reduction in total and visceral fat and in skeletal muscle lipid in both obesity and T2D.

  7. Self–reported diabetes education among Chinese middle–aged and older adults with diabetes

    PubMed Central

    Xu, Hanzhang; Luo, Jianfeng; Wu, Bei

    2016-01-01

    Background To compare self–reported diabetes education among Chinese middle–aged and older adults with diabetes in three population groups: urban residents, migrants in urban settings, and rural residents. Methods We used data from the 2011 China Health and Retirement Longitudinal Study. The sample included 993 participants age 45 and older who reported having diabetes diagnosed from a health professional. We performed multilevel regressions performed to examine the associations between characteristics and different aspects of diabetes education received. Findings Our study shows that 20.24% of the participants received no diabetes education at all. Among those who received information, 46.82% of respondents with diabetes received weight control advice from a health care provider, 90.97% received advice on exercise, 60.37% received diet advice, 35.12% were spoken to smoking control, and only 17.89% of persons were informed of foot care. After controlling socioeconomic factors, life style, number of comorbidities and community factors, we found that compared with migrant population and rural residents, urban residents were more likely to receive diabetes education on diet. Urban residents were also more likely to obtain diabetes education and more aspects of diabetes education comparison with migrants and rural residents. Conclusions Our study suggests diabetes education is a serious concern in China, and a significant proportion of the participants did not receive advice on smoking control and foot care. Rural residents and migrants from rural areas received much less diabetes education compared with urban residents. Efforts to improve diabetes educations are urgently needed in China.

  8. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain.

    PubMed

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases. PMID:27300264

  9. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

    PubMed Central

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn2+ affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases. PMID:27300264

  10. Onset Age of Obesity and Variables of Personality and Biography.

    ERIC Educational Resources Information Center

    Steinberg, Carol

    Three hypotheses derived from Hilde Bruch's formulations regarding onset differences among the obese were tested. In Bruch's theory, adult-onset, or reactive, obesity is a result of psychological trauma; the individual uses eating as a defense against anxiety and depression. Child-onset, or developmental, obesity results from a mixture of…

  11. Obesity, Type 2 Diabetes, and the Metabolic Syndrome: Pathophysiologic Relationships and Guidelines for Surgical Intervention.

    PubMed

    Genser, Laurent; Casella Mariolo, James Rossario; Castagneto-Gissey, Lidia; Panagiotopoulos, Spyros; Rubino, Francesco

    2016-08-01

    Several gastrointestinal (GI) operations originally developed for the treatment of severe obesity (bariatric surgery) promote sustained weight loss as well as dramatic, durable improvements of insulin-resistant states, most notably type 2 diabetes mellitus (T2DM). Experimental evidence shows that some rearrangements of GI anatomy can directly affect glucose homeostasis, insulin sensitivity, and inflammation, supporting the idea that the GI tract is a biologically rational target for interventions aimed at correcting pathophysiologic aspects of cardiometabolic disorders. This article reviews the pathophysiology of metabolic disease and the role of bariatric/metabolic surgery in current clinical guidelines for the treatment of obesity and T2DM. PMID:27473795

  12. Targeting adipose tissue in the treatment of obesity-associated diabetes.

    PubMed

    Kusminski, Christine M; Bickel, Perry E; Scherer, Philipp E

    2016-09-01

    Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis. PMID:27256476

  13. The Role of Organelle Stresses in Diabetes Mellitus and Obesity: Implication for Treatment

    PubMed Central

    Chang, Yi-Cheng; Hee, Siow-Wey; Hsieh, Meng-Lun; Jeng, Yung-Ming; Chuang, Lee-Ming

    2015-01-01

    The type 2 diabetes pandemic in recent decades is a huge global health threat. This pandemic is primarily attributed to the surplus of nutrients and the increased prevalence of obesity worldwide. In contrast, calorie restriction and weight reduction can drastically prevent type 2 diabetes, indicating a central role of nutrient excess in the development of diabetes. Recently, the molecular links between excessive nutrients, organelle stress, and development of metabolic disease have been extensively studied. Specifically, excessive nutrients trigger endoplasmic reticulum stress and increase the production of mitochondrial reactive oxygen species, leading to activation of stress signaling pathway, inflammatory response, lipogenesis, and pancreatic beta-cell death. Autophagy is required for clearance of hepatic lipid clearance, alleviation of pancreatic beta-cell stress, and white adipocyte differentiation. ROS scavengers, chemical chaperones, and autophagy activators have demonstrated promising effects for the treatment of insulin resistance and diabetes in preclinical models. Further results from clinical trials are eagerly awaited. PMID:26613076

  14. Carbon Dioxide Emissions and Change in Prevalence of Obesity and Diabetes in the United States: An Ecological Study

    PubMed Central

    Zheutlin, Alexander R.; Adar, Sara D.; Park, Sung Kyun

    2014-01-01

    Recent studies suggest that increasing levels of the greenhouse gas, carbon dioxide (CO2), may influence weight gain and thus may play a role in rising trends in obesity and diabetes. We conducted an ecological study to examine the associations between CO2 emissions from fossil fuel combustion and changes in the prevalence of obesity and diabetes in the United States. County-level data on CO2 emissions, prevalence of obesity and diagnosed diabetes, other sociodemographic factors and neighborhood characteristics related to urbanicity, and fine particles (PM2.5) between 2004 and 2008 were obtained from the Vulcan Project, Centers for Disease Control and Prevention, and American Community Survey. Linear mixed effect modeling of 3019 counties for the associations between average CO2 emissions and changes in diabetes and obesity prevalence between 2004 and 2008 was performed. The average obesity and diabetes prevalence increased between 2004 and 2008 by 3.65% (SD: 1.88%) and 1.65% (SD: 1.70%), respectively. A marginally significant positive association between CO2 emission and changes in obesity prevalence was found with adjustment for sociodemographic factors, indicators of urbanicity and spatial autocorrelation (p-trend=0.06). The association became weaker and nonsignificant with further adjustment for PM2.5 (p-trend=0.17). There was a significant positive association between CO2 emission and changes in diabetes prevalence before controlling for PM2.5 (p-trend=0.05) but the association became null after controlling for PM2.5 (p-trend=0.49), suggesting PM2.5 is a critical confounder in the association between CO2 emission and changes in diabetes prevalence. This study does not support the hypothesis that CO2 emissions, a leading driver of climate change, may be linked to increasing trends in obesity and diabetes, though there was an indication of possible link between CO2 and obesity. PMID:25108606

  15. Carbon dioxide emissions and change in prevalence of obesity and diabetes in the United States: an ecological study.

    PubMed

    Zheutlin, Alexander R; Adar, Sara D; Park, Sung Kyun

    2014-12-01

    Recent studies suggest that increasing levels of the greenhouse gas, carbon dioxide (CO2), may influence weight gain and thus may play a role in rising trends in obesity and diabetes. We conducted an ecological study to examine the associations between CO2 emissions from fossil fuel combustion and changes in the prevalence of obesity and diabetes in the United States. County-level data on CO2 emissions, prevalence of obesity and diagnosed diabetes, other sociodemographic factors and neighborhood characteristics related to urbanicity, and fine particles (PM2.5) between 2004 and 2008 were obtained from the Vulcan Project, Centers for Disease Control and Prevention, and American Community Survey. Linear mixed effect modeling of 3019 counties for the associations between average CO2 emissions and changes in diabetes and obesity prevalence between 2004 and 2008 was performed. The average obesity and diabetes prevalence increased between 2004 and 2008 by 3.65% (SD: 1.88%) and 1.65% (SD: 1.70%), respectively. A marginally significant positive association between CO2 emission and changes in obesity prevalence was found with adjustment for sociodemographic factors, indicators of urbanicity and spatial autocorrelation (p-trend=0.06). The association became weaker and nonsignificant with further adjustment for PM2.5 (p-trend=0.17). There was a significant positive association between CO2 emission and changes in diabetes prevalence before controlling for PM2.5 (p-trend=0.05) but the association became null after controlling for PM2.5 (p-trend=0.49), suggesting that PM2.5 is a critical confounder in the association between CO2 emission and changes in diabetes prevalence. This study does not support the hypothesis that CO2 emissions, a leading driver of climate change, may be linked to increasing trends in obesity and diabetes, though there was an indication of possible link between CO2 and obesity.

  16. Primary prevention of gestational diabetes for women who are overweight and obese: a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Gestational Diabetes Mellitus (GDM) has well recognised adverse health implications for the mother and her newborn that are both short and long term. Obesity is a significant risk factor for developing GDM and the prevalence of obesity is increasing globally. It is a matter of public health importance that clinicians have evidence based strategies to inform practice and currently there is insufficient evidence regarding the impact of dietary and lifestyle interventions on improving maternal and newborn outcomes. The primary aim of this study is to measure the impact of a telephone based intervention that promotes positive lifestyle modifications on the incidence of GDM. Secondary aims include: the impact on gestational weight gain; large for gestational age babies; differences in blood glucose levels taken at the Oral Glucose Tolerance Test (OGTT) and selected factors relating to self-efficacy and psychological wellbeing. Method/design A randomised controlled trial (RCT) will be conducted involving pregnant women who are overweight (BMI >25 to 29.9 k/gm2) or obese (BMI >30 kgm/2), less than 14 weeks gestation and recruited from the Barwon South West region of Victoria, Australia. From recruitment until birth, women in the intervention group will receive a program informed by the Theory of Self-efficacy and employing Motivational Interviewing. Brief ( less than 5 minute) phone contact will alternate with a text message/email and will involve goal setting, behaviour change reinforcement with weekly weighing and charting, and the provision of health information. Those in the control group will receive usual care. Data for primary and secondary outcomes will be collected from medical record review and a questionnaire at 36 weeks gestation. Discussion Evidence based strategies that reduce the incidence of GDM are a priority for contemporary maternity care. Changing health behaviours is a complex undertaking and trialling a composite intervention that

  17. Exercise dose and diabetes risk in overweight and obese children: A randomized, controlled trial

    PubMed Central

    Davis, Catherine L; Pollock, Norman K; Waller, Jennifer L; Allison, Jerry D; Dennis, B Adam; Bassali, Reda; Meléndez, Agustín; Boyle, Colleen A; Gower, Barbara A

    2012-01-01

    Context Pediatric studies showed that aerobic exercise reduces metabolic risk, but dose response information is not available. Objective Test the effect of aerobic training dose on insulin resistance, fatness, visceral fat, and fitness in overweight, sedentary children, and test moderation by sex and race. Design, Setting, and Participants Randomized, controlled, efficacy trial from 2003 through 2007, in which 222 overweight or obese, sedentary children (mean age, 9.4 yrs; 42% male, 58% black) were recruited from 15 public schools in the Augusta, GA area. Intervention Low-dose (20 min/d, n = 71) or high-dose (40 min/d, n = 73) aerobic training (13 ± 1.6 wk, 5 d/wk), or control condition (usual physical activity, n = 78); 94% retention. Main outcome measures Prespecified primary outcomes were type 2 diabetes risk at posttest, assessed by insulin area under the curve (AUC) from oral glucose tolerance test, aerobic fitness, percent body fat via dual-energy x-ray absorptiometry, and visceral fat via magnetic resonance, analyzed by intent-to-treat. Results Most children (85%) were obese. At baseline, the mean BMI was 26 (SD = 4.4). Reductions in insulin AUC were larger in the high-dose (adjusted mean difference [95% CI], −3.56 [−6.26 to −0.85], P = .01) than low-dose group (−2.96 [−5.69 to −0.22], P = .03) ×103 μU/mL) vs control group. Dose-response trends were also observed for body fat (−1.4 [−2.2 to −0.7], P < .001; −0.8 [−1.6 to −0.07] %, P =.03) and visceral fat (−3.9 [−6.0 to −1.7], P < .001; −2.8 [−4.9 to −0.6] cm3, P = .01) in the high- and low-dose vs control groups, respectively. Effects in the high- and low-dose groups vs control were similar for fitness (2.4 [0.4 to 4.5], P =.02; 2.4 [0.3 to 4.5] mL/kg/min, P = .03). High- vs. low-dose group effects were similar for these outcomes. There was no moderation by sex or race. Conclusions Three months of 20 or 40 min/d aerobic training improved fitness, and demonstrated dose

  18. Transgenerational effects of obesity and malnourishment on diabetes risk in F2 generation.

    PubMed

    Hanafi, Mervat Y; Saleh, Moustafa M; Saad, Mohamed I; Abdelkhalek, Taha M; Kamel, Maher A

    2016-01-01

    Transgenerational inheritance of various diseases and phenotypes has been demonstrated in diverse species and involves various epigenetic markers. Obesity and malnourishment are nutritional stresses that have effects on offspring through increasing their risk of diabetes and/or obesity. Obesity and malnourishment both affect glucose metabolism and alter oxidative stress parameters in key organs. We induced obesity and malnutrition in F0 female rats by the use of obesogenic diet and protein-deficient diet, respectively. F0 obese and malnourished females were mated with control males and their offspring (F1 generation) were maintained on control diets. The male and female F1 offspring were mated with controls and the resultant offspring (F2 generation) were maintained on control diet. Glucose-sensing markers, glucose metabolism, indicators of insulin resistance and oxidative stress parameters were assessed during fetal development and till the adulthood of the offspring. Glucose-sensing genes were significantly over-expressed in distinct fetal tissues of F2 offspring of malnourished F1 females (F2-MF1F), specifically in fetal pancreas, liver, and adipose tissue. Nuclear and mitochondrial 8-oxo-dG DNA content was significantly elevated in F2-MF1F fetal pancreas. Maternal FBG was significantly elevated in F2-MF1F and F2 offspring of obese F1 females (F2-OF1F) during pregnancy. Males and females offspring of F2-OF1 exhibited significantly elevated FBG and impaired OGTT. Offspring of F2-MF1F showed similar results, while that of F2-MF1M did not significantly deviate from controls. F2-OF1F and F2-MF1F offspring exhibited significant deviation in insulin levels and HOMA-IR levels from controls. Malnourishment has a stronger transgenerational effect through maternal line compared to obesity and malnourishment through paternal line in increasing risk of diabetes in F2 generation.

  19. Estimating the risk of type-2 diabetes using obese-years in a contemporary population of the Framingham Study

    PubMed Central

    Abdullah, Asnawi; Amin, Fauzi Ali; Hanum, Farida; Stoelwinder, Johannes; Tanamas, Stephanie; Wolf, Rory; Wong, Evelyn; Peeters, Anna

    2016-01-01

    Background We have recently demonstrated that an obese-years construct is a better predictor of the risk of diabetes than the severity of body weight alone. However, these risk estimates were derived from a population cohort study initiated in 1948 that might not apply to the current population. Objective To validate an obese-years construct in estimating the risk of type-2 diabetes in a more contemporary cohort study. Design A total of 5,132 participants of the Framingham Offspring Study, initiated in 1972, were followed up for 45 years. Body mass index (BMI) above 29 kg/m2 was multiplied by the number of years lived with obesity at that BMI to define the number of obese-years. Time-dependent Cox regression was used to explore the association. Results The risk of type-2 diabetes increased significantly with increase in obese-years. Adjusted hazard ratios increased by 6% (95% CI: 5–7%) per additional 10 points of obese-years. This ratio was observed to be similar in both men and women, but was 4% higher in current smokers than in never/ex-smokers. The Akaike Information Criterion confirmed that the Cox regression model with the obese-years construct was a stronger predictor of the risk of diabetes than a model including either BMI or the duration of obesity alone. Conclusions In a contemporary cohort population, it was confirmed that the obese-years construct is strongly associated with an increased risk of type-2 diabetes. This suggests that both severity and the duration of obesity should be considered in future estimations of the burden of disease associated with obesity. PMID:27369220

  20. Obesity and diabetes as accelerators of functional decline: can lifestyle interventions maintain functional status in high risk older adults?

    PubMed

    Anton, Stephen D; Karabetian, Christy; Naugle, Kelly; Buford, Thomas W

    2013-09-01

    Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and treatment of physical disability in these persons have become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes.

  1. Type 1 and Type 2 Diabetes Preconception and in Pregnancy: Health Impacts, Influence of Obesity and Lifestyle, and Principles of Management.

    PubMed

    Abell, Sally K; Nankervis, Alison; Khan, Khalid S; Teede, Helena J

    2016-03-01

    Preexisting diabetes in pregnancy results in increased risks to the mother, fetus, and neonate. Preconception care is vital to reduce risk of miscarriage, congenital malformations, and perinatal mortality. Preconception care should empower women with realistic goal setting, healthy lifestyle, and diabetes self-management skills, to ensure a positive experience of the pregnancy and to reduce diabetes-related distress. In high-risk women without known diabetes, preconception and early antenatal screening is crucial to enable prompt treatment of hyperglycemia and any complications. The prevalence of obesity in reproductive age women is rising, further increasing risk of poor pregnancy outcomes in women with diabetes. Adverse lifestyle factors should be addressed preconception and in the antenatal period, allowing opportunity to improve physical health, manage weight, and improve neonatal outcomes. Management of diabetes in pregnancy involves individualized and intensified insulin therapy, accounting for expected changes in insulin sensitivity, and minimizing glucose variability and hypoglycemia. Diabetes complications must be screened for and managed as necessary. Delivery timing will depend on fetal surveillance and obstetric considerations. It is important to maintain engagement and motivation of these women in the postpartum period, encouraging breastfeeding and postpartum weight management and supporting diabetes management.

  2. Interventional treatment of obesity and diabetes: An interim report on gastric electrical stimulation.

    PubMed

    Lebovitz, Harold E

    2016-03-01

    Gastric electrical stimulation has been applied to treat human obesity since 1995. Dilatation of the stomach causes a series of neural reflexes which result in satiation and satiety. In non-obese individuals food ingestion is limited in part by this mechanism. In obese individuals, satiation and satiety are defective and unable to limit energy intake and prevent excessive weight gain. Several gastric electrical stimulatory (GES) devices have been developed, tested in clinical trials and even approved for the treatment of obesity. The design and clinical utility of three devices (Transend®, Maestro® and DIAMOND®) that have been extensively studied are presented as well as that of a new device (abiliti®) which is in early development. The Transcend®, a low energy GES device, showed promising results in open label studies but failed to show a difference from placebo in decreasing weight in obese subjects. The results of the clinical trials in treating obese subjects with the Maestro®, a vagal nerve stimulator, were sufficient to gain approval for marketing the device. The DIAMOND®, a multi-electrode GES device, has been used to treat type 2 diabetes and an associated benefit is to reduce body weight and lower systolic blood pressure. PMID:27106829

  3. Role of gut microbiota in obesity, type 2 diabetes and Alzheimer's disease.

    PubMed

    Naseer, Muhammad I; Bibi, Fehmida; Alqahtani, Mohammed H; Chaudhary, Adeel G; Azhar, Esam I; Kamal, Mohammad A; Yasir, Muhammad

    2014-03-01

    In recent years, there is a growing interest in research to investigate the importance of gut microbiome in health and diseases. This opens a new area of research for the role of microbial flora of the human gut in inflammation, energy homeostasis, pathogenesis of obesity and other associated disorders. Recent studies propose association of the gut microbiome with development of obesity and metabolic syndromes, such as type 2 diabetes mellitus (T2DM). The T2DM is a metabolic disease that is mainly caused by obesity-linked insulin resistance. The vascular effects of obesity appears to play a role in the development of Alzheimer's disease (AD) that is one of the rapidly growing diseases of a late stage of life all over the world. Studies from both humans and mice models have been demonstrated the engagement of gut microbial flora in the pathogenesis of obesity and host metabolism. The aim of this review is to discuss the current findings that may explain the cascade of gut microbial flora participation in the development of obesity, T2DM and further initiation of AD. In addition, the available data regarding the mechanisms that have been proposed to elucidate the role of gut microbiota in weight gain and possible cause of T2DM and AD have been examined.

  4. Effects of Long-Term Testosterone Therapy on Patients with “Diabesity”: Results of Observational Studies of Pooled Analyses in Obese Hypogonadal Men with Type 2 Diabetes

    PubMed Central

    Haider, Ahmad; Yassin, Aksam; Doros, Gheorghe; Saad, Farid

    2014-01-01

    To investigate effects of long-term testosterone (T) therapy in obese men with T deficiency (TD) and type 2 diabetes mellitus (T2DM), data were collected from two observational, prospective, and cumulative registry studies of 561 men with TD receiving T therapy for up to 6 years. A subgroup of obese hypogonadal men with T2DM was analyzed. Weight, height, waist circumference (WC), fasting blood glucose (FBG), glycated haemoglobin (HbA1c) blood pressure, lipid profile, C-reactive protein (CRP), and liver enzymes were measured. A total of 156 obese, diabetic men with T deficiency, aged 61.17 ± 6.18 years, fulfilled selection criteria. Subsequent to T therapy, WC decreased by 11.56 cm and weight declined by 17.49 kg (15.04%). Fasting glucose declined from 7.06 ± 1.74 to 5.59 ± 0.94 mmol/L (P < 0.0001 for all). HbA1c decreased from 8.08 to 6.14%, with a mean change of 1.93%. Systolic and diastolic blood pressure, lipid profiles including total cholesterol: HDL ratio, CRP, and liver enzymes all improved (P < 0.0001). Long-term T therapy for up to 6 years resulted in significant and sustained improvements in weight, T2DM, and other cardiometabolic risk factors in obese, diabetic men with TD and this therapy may play an important role in the management of obesity and diabetes (diabesity) in men with T deficiency. PMID:24738000

  5. Glucose, Obesity, Metabolic Syndrome, and Diabetes: Relevance to Incidence of Heart Failure

    PubMed Central

    Horwich, Tamara B.; Fonarow, Gregg C.

    2010-01-01

    Heart failure (HF) is common, results in poor clinical outcomes, and is associated with large health-care costs. The incidence of HF continues to rise, with approximately 670,000 new cases per year and a 20% lifetime risk of HF for persons 40 years and older in the United States. Risk factors for HF have been identified and thus preventative strategies should have a positive effect on disease burden, morbidity, and mortality. Although coronary artery disease and hypertension have traditionally been considered among the most important modifiable risk factors for the development of HF, recent studies have highlighted the importance of increasingly prevalent metabolic risk factors – glucose, diabetes, obesity, and the metabolic syndrome. This paper will present evidence for the link between glucose, diabetes, obesity, metabolic syndrome and incident HF. Furthermore, we will discuss how risk factor modification and other preventive therapies may help curb the rising incidence of HF. PMID:20117431

  6. The DIAMOND system in the treatment of type 2 diabetes mellitus in an obese patient.

    PubMed

    Kozakowski, Jarosław; Lebovitz, Harold E; Kiciak, Adam; Zgliczyński, Wojciech; Tarnowski, Wiesław

    2014-12-01

    Obesity and type 2 diabetes mellitus have reached epidemic proportions worldwide. As the majority of antidiabetic medications are of limited efficacy and patient adherence to long-term therapy is one of the main limiting factors of effective blood glucose and body weight control, new therapies are still looked for. The DIAMOND system seems to be one of the most promising among them. This system recognizes natural electrical activity of the stomach and automatically applies electrical stimulation treatment during/after eating with subsequent modulation of signals transmitted to the regulatory centers in the brain in order to provoke an early response of the gut typical of a full meal. We present the case of a 47-year-old obese woman with type 2 diabetes. During treatment with this system, serum glucose and hemoglobin A1c levels significantly decreased. Body weight loss and waist circumference reduction were observed. Additionally, beneficial effect on lipid profile was found.

  7. The DIAMOND system in the treatment of type 2 diabetes mellitus in an obese patient.

    PubMed

    Kozakowski, Jarosław; Lebovitz, Harold E; Kiciak, Adam; Zgliczyński, Wojciech; Tarnowski, Wiesław

    2014-12-01

    Obesity and type 2 diabetes mellitus have reached epidemic proportions worldwide. As the majority of antidiabetic medications are of limited efficacy and patient adherence to long-term therapy is one of the main limiting factors of effective blood glucose and body weight control, new therapies are still looked for. The DIAMOND system seems to be one of the most promising among them. This system recognizes natural electrical activity of the stomach and automatically applies electrical stimulation treatment during/after eating with subsequent modulation of signals transmitted to the regulatory centers in the brain in order to provoke an early response of the gut typical of a full meal. We present the case of a 47-year-old obese woman with type 2 diabetes. During treatment with this system, serum glucose and hemoglobin A1c levels significantly decreased. Body weight loss and waist circumference reduction were observed. Additionally, beneficial effect on lipid profile was found. PMID:25562004

  8. Insights into Obesity and Diabetes at the Intersection of Mouse and Human Genetics

    PubMed Central

    Kebede, Melkam A.; Attie, Alan D.

    2014-01-01

    Many of our insights into obesity and diabetes come from studies in mice carrying natural or induced mutations. In parallel, genome-wide association studies in humans have identified numerous genes that are causally associated with obesity and diabetes, but discovering the underlying mechanisms required in-depth studies in mice. We discuss the advantages of studying natural variation in mice and summarize several examples where the combination of human and mouse genetics opened windows into fundamental physiological pathways. A noteworthy example is the melanocortin-4 receptor and its role in energy balance. The pathway was delineated by discovering the gene responsible for the Agouti mutation in mice. With more targeted phenotyping, we predict that additional pathways relevant to human pathophysiology will discovered. PMID:25034129

  9. Corticosteroid-mediated programming and the pathogenesis of obesity and diabetes.

    PubMed

    Reynolds, Rebecca M

    2010-10-01

    Epidemiological studies have shown that low birthweight is associated with increased risk of development of diabetes and obesity in later life. Over-exposure of the developing fetus to glucocorticoids is one of the major hypotheses that has been proposed to explain this association. In animal models, a range of manipulations that increase fetal glucocorticoid load, 'programme' permanent changes in glucose and insulin metabolism and adiposity. This may be mediated by alterations in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In humans, low birthweight is associated with increased circulating glucocorticoid levels, and an increased cortisol response to physiological and psychosocial stressors, in child- and adulthood. This activation of the HPA axis is also associated with increased risk of development of diabetes and obesity in later life.

  10. Evidence that dirty electricity is causing the worldwide epidemics of obesity and diabetes.

    PubMed

    Milham, Samuel

    2014-01-01

    The epidemics of obesity and diabetes most apparent in recent years had their origins with Thomas Edison's development of distributed electricity in New York City in 1882. His original direct current (DC) generators suffered serious commutator brush arcing which is a major source of high-frequency voltage transients (dirty electricity). From the onset of the electrical grid, electrified populations have been exposed to dirty electricity. Diesel generator sets are a major source of dirty electricity today and are used almost universally to electrify small islands and places unreachable by the conventional electric grid. This accounts for the fact that diabetes prevalence, fasting plasma glucose and obesity are highest on small islands and other places electrified by generator sets and lowest in places with low levels of electrification like sub-Saharan Africa and east and Southeast Asia.

  11. 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.

  12. The Human Gut Microbiome and Body Metabolism: Implications for Obesity and Diabetes

    PubMed Central

    Devaraj, Sridevi; Hemarajata, Peera; Versalovic, James

    2014-01-01

    BACKGROUND Obesity, metabolic syndrome, and type 2 diabetes are major public health challenges. Recently, interest has surged regarding the possible role of the intestinal microbiota as potential novel contributors to the increased prevalence of these 3 disorders. CONTENT Recent advances in microbial DNA sequencing technologies have resulted in the widespread application of whole-genome sequencing technologies for metagenomic DNA analysis of complex ecosystems such as the human gut. Current evidence suggests that the gut microbiota affect nutrient acquisition, energy harvest, and a myriad of host metabolic pathways. CONCLUSION Advances in the Human Microbiome Project and human metagenomics research will lead the way toward a greater understanding of the importance and role of the gut microbiome in metabolic disorders such as obesity, metabolic syndrome, and diabetes. PMID:23401286

  13. Obesity and Alzheimer's disease: a link between body weight and cognitive function in old age.

    PubMed

    Naderali, Ebrahim K; Ratcliffe, Stuart H; Dale, Mark C

    Obesity is now a global health hazard. It not only predisposes to an array of risk factors leading to increased morbidity and mortality amongst adults but it also has a major negative impact on children's health. The deleterious effects of obesity on cardiovascular system have now been well acknowledged. It causes insulin resistance that in turn leads to diabetes, hypertension and cardiovascular abnormalities. The vascular effects of obesity may have a role in the development of a rapidly growing disease of late life, Alzheimer's disease. The precise mechanisms of the association between adiposity and impairment of cognitive performance remain to be elucidated. However, negative impact of obesity on cognitive function may be, at least in part, due to vascular defects, impaired insulin metabolism and signaling pathway or a defect in glucose transport mechanisms in brain. This review examines the available data regarding the impact of obesity on cognitive function.

  14. Advances in the Science, Treatment, and Prevention of the Disease of Obesity: Reflections From a Diabetes Care Editors' Expert Forum.

    PubMed

    Cefalu, William T; Bray, George A; Home, Philip D; Garvey, W Timothy; Klein, Samuel; Pi-Sunyer, F Xavier; Hu, Frank B; Raz, Itamar; Van Gaal, Luc; Wolfe, Bruce M; Ryan, Donna H

    2015-08-01

    As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave concern. In June 2014, a Diabetes Care Editors' Expert Forum convened to review the state of obesity research and discuss the latest prevention initiatives and behavioral, medical, and surgical therapies. This article, an outgrowth of the forum, offers an expansive view of the obesity epidemic, beginning with a discussion of its root causes. Recent insights into the genetic and physiological factors that influence body weight are reviewed, as are the pathophysiology of obesity-related metabolic dysfunction and the concept of metabolically healthy obesity. The authors address the crucial question of how much weight loss is necessary to yield meaningful benefits. They describe the challenges of behavioral modification and predictors of its success. The effects of diabetes pharmacotherapies on body weight are reviewed, including potential weight-neutral combination therapies. The authors also summarize the evidence for safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The article concludes with an impassioned call for researchers, clinicians, governmental agencies, health policymakers, and health-related industries to collectively embrace the urgent mandate to improve prevention and treatment and for society at large to acknowledge and manage obesity as a serious disease. PMID:26421334

  15. Advances in the Science, Treatment, and Prevention of the Disease of Obesity: Reflections From a Diabetes Care Editors’ Expert Forum

    PubMed Central

    Bray, George A.; Home, Philip D.; Garvey, W. Timothy; Klein, Samuel; Pi-Sunyer, F. Xavier; Hu, Frank B.; Raz, Itamar; Van Gaal, Luc; Wolfe, Bruce M.; Ryan, Donna H.

    2015-01-01

    As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave concern. In June 2014, a Diabetes Care Editors’ Expert Forum convened to review the state of obesity research and discuss the latest prevention initiatives and behavioral, medical, and surgical therapies. This article, an outgrowth of the forum, offers an expansive view of the obesity epidemic, beginning with a discussion of its root causes. Recent insights into the genetic and physiological factors that influence body weight are reviewed, as are the pathophysiology of obesity-related metabolic dysfunction and the concept of metabolically healthy obesity. The authors address the crucial question of how much weight loss is necessary to yield meaningful benefits. They describe the challenges of behavioral modification and predictors of its success. The effects of diabetes pharmacotherapies on body weight are reviewed, including potential weight-neutral combination therapies. The authors also summarize the evidence for safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The article concludes with an impassioned call for researchers, clinicians, governmental agencies, health policymakers, and health-related industries to collectively embrace the urgent mandate to improve prevention and treatment and for society at large to acknowledge and manage obesity as a serious disease. PMID:26421334

  16. Influence of whole-wheat consumption on fecal microbial community structure of obese diabetic mice

    PubMed Central

    Ivanov, Ivan; Mills, David A.

    2016-01-01

    The digestive tract of mammals and other animals is colonized by trillions of metabolically-active microorganisms. Changes in the gut microbiota have been associated with obesity in both humans and laboratory animals. Dietary modifications can often modulate the obese gut microbial ecosystem towards a more healthy state. This phenomenon should preferably be studied using dietary ingredients that are relevant to human nutrition. This study was designed to evaluate the influence of whole-wheat, a food ingredient with several beneficial properties, on gut microorganisms of obese diabetic mice. Diabetic (db/db) mice were fed standard (obese-control) or whole-wheat isocaloric diets (WW group) for eight weeks; non-obese mice were used as control (lean-control). High-throughput sequencing using the MiSeq platform coupled with freely-available computational tools and quantitative real-time PCR were used to analyze fecal bacterial 16S rRNA gene sequences. Short-chain fatty acids were measured in caecal contents using quantitative high-performance liquid chromatography photo-diode array analysis. Results showed no statistical difference in final body weights between the obese-control and the WW group. The bacterial richness (number of Operational Taxonomic Units) did not differ among the treatment groups. The abundance of Ruminococcaceae, a family containing several butyrate-producing bacteria, was found to be higher in obese (median: 6.9%) and WW-supplemented mice (5.6%) compared to lean (2.7%, p = 0.02, Kruskal-Wallis test). Caecal concentrations of butyrate were higher in obese (average: 2.91 mmol/mg of feces) but especially in WW-supplemented mice (4.27 mmol/mg) compared to lean controls (0.97 mmol/mg), while caecal succinic acid was lower in the WW group compared to obese but especially to the lean group. WW consumption was associated with ∼3 times higher abundances of Lactobacillus spp. compared to both obese and lean control mice. Analysis of weighted Uni

  17. Influence of whole-wheat consumption on fecal microbial community structure of obese diabetic mice.

    PubMed

    Garcia-Mazcorro, Jose F; Ivanov, Ivan; Mills, David A; Noratto, Giuliana

    2016-01-01

    The digestive tract of mammals and other animals is colonized by trillions of metabolically-active microorganisms. Changes in the gut microbiota have been associated with obesity in both humans and laboratory animals. Dietary modifications can often modulate the obese gut microbial ecosystem towards a more healthy state. This phenomenon should preferably be studied using dietary ingredients that are relevant to human nutrition. This study was designed to evaluate the influence of whole-wheat, a food ingredient with several beneficial properties, on gut microorganisms of obese diabetic mice. Diabetic (db/db) mice were fed standard (obese-control) or whole-wheat isocaloric diets (WW group) for eight weeks; non-obese mice were used as control (lean-control). High-throughput sequencing using the MiSeq platform coupled with freely-available computational tools and quantitative real-time PCR were used to analyze fecal bacterial 16S rRNA gene sequences. Short-chain fatty acids were measured in caecal contents using quantitative high-performance liquid chromatography photo-diode array analysis. Results showed no statistical difference in final body weights between the obese-control and the WW group. The bacterial richness (number of Operational Taxonomic Units) did not differ among the treatment groups. The abundance of Ruminococcaceae, a family containing several butyrate-producing bacteria, was found to be higher in obese (median: 6.9%) and WW-supplemented mice (5.6%) compared to lean (2.7%, p = 0.02, Kruskal-Wallis test). Caecal concentrations of butyrate were higher in obese (average: 2.91 mmol/mg of feces) but especially in WW-supplemented mice (4.27 mmol/mg) compared to lean controls (0.97 mmol/mg), while caecal succinic acid was lower in the WW group compared to obese but especially to the lean group. WW consumption was associated with ∼3 times higher abundances of Lactobacillus spp. compared to both obese and lean control mice. Analysis of weighted Uni

  18. Impact of Gut Microbiota on Obesity, Diabetes, and Cardiovascular Disease Risk.

    PubMed

    Miele, Luca; Giorgio, Valentina; Alberelli, Maria Adele; De Candia, Erica; Gasbarrini, Antonio; Grieco, Antonio

    2015-12-01

    Gut microbiota has been recently established to have a contributory role in the development of cardiometabolic disorders, such as atherosclerosis, obesity, and type 2 diabetes. Growing interest has focused on the modulation of gut microbiota as a therapeutic strategy in cardiovascular diseases and metabolic disorders. In this paper, we have reviewed the impact of gut microbiota on metabolic disorders and cardiovascular disease risk, focusing on the newest findings in this field. PMID:26497040

  19. CREBRF variant increases obesity risk and protects against diabetes in Samoans.

    PubMed

    Loos, Ruth J F

    2016-08-30

    A genome-wide study in Samoans has identified a protein-altering variant (p.Arg475Gln) in CREBRF as being associated with 1.3-fold increased risk of obesity and, intriguingly, 1.6-fold decreased risk of type 2 diabetes. This variant, which is common among Samoans (minor allele frequency = 26%) but extremely rare in other populations, promotes fat storage and reduces energy use in cellular models. PMID:27573685

  20. Insulin Suppresses TNF-dependent Early Osteoarthritic Changes Associated with Obesity and Type 2 Diabetes

    PubMed Central

    Hamada, Daisuke; Maynard, Robert; Schott, Eric; Drinkwater, Christopher J.; Ketz, John P.; Kates, Stephen L.; Jonason, Jennifer H.; Hilton, Matthew J.; Zuscik, Michael J.; Mooney, Robert A.

    2015-01-01

    Objective Obesity is a chronic inflammatory state that is associated with insulin resistance and type 2 diabetes (T2D), as well as an increased risk for osteoarthritis (OA). To define the links between inflammation of obesity, insulin resistance, and OA, two hypotheses were tested: 1) TNF is critical in mediating these OA changes and 2) insulin has direct effects on the synovial joint that are compromised by insulin resistance. Methods Effects of TNF and insulin on catabolic gene expression were determined in fibroblast-like synoviocytes (FLSs) isolated from human osteoarthritic synovium. Synovial TNF expression and OA progression were examined in high fat-fed (HF) obese/T2D mice and TNF knockout mice. Insulin resistance was investigated in synovium from T2D patients. Results Insulin receptors (IR) were abundant in mouse and human synovial membrane. FLSs were insulin responsive with dose dependent phosphorylation of IR and Akt. While TNF markedly increased expression and release of MMP1, MMP13, and ADAMTS4 by FLSs, insulin selectively inhibited the effects by >50%. TNF expression and abundance were elevated in synovium from obese, T2D mice. In TNF knockout mice, increases in osteophyte formation and synovial hyperplasia associated with HF diet were blunted. Synovium from diabetic patients contained markedly more macrophages, TNF levels were elevated, and insulin-dependent phosphorylation of IR and Akt was blunted compared to non-diabetics. Conclusion TNF appears involved in mediating the advanced progression of OA seen in T2D. While insulin plays a protective, anti-inflammatory role in the synovium, insulin resistance of diabetes may impair this protective effect and promote OA. PMID:26713606

  1. Impact of Gut Microbiota on Obesity, Diabetes, and Cardiovascular Disease Risk.

    PubMed

    Miele, Luca; Giorgio, Valentina; Alberelli, Maria Adele; De Candia, Erica; Gasbarrini, Antonio; Grieco, Antonio

    2015-12-01

    Gut microbiota has been recently established to have a contributory role in the development of cardiometabolic disorders, such as atherosclerosis, obesity, and type 2 diabetes. Growing interest has focused on the modulation of gut microbiota as a therapeutic strategy in cardiovascular diseases and metabolic disorders. In this paper, we have reviewed the impact of gut microbiota on metabolic disorders and cardiovascular disease risk, focusing on the newest findings in this field.

  2. Obesity and diabetes in vulnerable populations: reflection on proximal and distal causes.

    PubMed

    Candib, Lucy M

    2007-01-01

    Around the world obesity and diabetes are climbing to epidemic proportion, even in countries previously characterized by scarcity. Likewise, people from low-income and minority communities, as well as immigrants from the developing world, increasingly visit physicians in North America with obesity, metabolic syndrome, or diabetes. Explanations limited to lifestyle factors such as diet and exercise are inadequate to explain the universality of what can be called a syndemic, a complex and widespread phenomenon in population health produced by multiple reinforcing conditions. Underlying the problem are complex factors-genetic, physiological, psychological, familial, social, economic, and political-coalescing to overdetermine these conditions. These interacting factors include events occurring during fetal life, maternal physiology and life context, the thrifty genotype, the nutritional transition, health impact of urbanization and immigration, social attributions and cultural perceptions of increased weight, and changes in food costs and availability resulting from globalization. Better appreciation of the complexity of causation underlying the worldwide epidemic of obesity and diabetes can refocus the work of clinicians and researchers to work at multiple levels to address prevention and treatment for these conditions among vulnerable populations. PMID:18025493

  3. Physical activity in children: prevention of obesity and type 2 diabetes.

    PubMed

    Rush, Elaine; Simmons, David

    2014-01-01

    There is strong evidence that increased physical activity is beneficial for blood glucose homeostasis and the prevention of obesity and type 2 diabetes mellitus. This chapter takes a life course approach with an emphasis on the intrauterine and childhood stages of life. Firstly, growth and development at critical periods with a focus on skeletal muscle and adipose tissue; then, obesity and type 2 diabetes mellitus are considered in relation to physical activity and sedentary behaviour. The importance of the development of fundamental movement skills in early childhood for both physical fitness and also growth and development is emphasised. Physical activity guidelines in westernised countries are examined for commonalities. Finally, the effective translation of the evidence base for the benefits of physical activity into randomised controlled trials and then into real-world public health services that are sustainable is addressed with a case study from New Zealand of Project Energize--a through-school physical activity and nutrition intervention. Physical activity, alongside a 'healthy diet' is arguably the best preventive measure and treatment for both obesity and type 2 diabetes. It is an essential and normal activity of daily life, and all aspects of the life course and the environment should support physical activity.

  4. Blood cadmium in Chinese adults and its relationships with diabetes and obesity.

    PubMed

    Nie, Xiaomin; Wang, Ningjian; Chen, Yi; Chen, Chi; Han, Bing; Zhu, Chunfang; Chen, Yingchao; Xia, Fangzhen; Cang, Zhen; Lu, Meng; Meng, Ying; Jiang, Boren; D Jensen, Michael; Lu, Yingli

    2016-09-01

    The aim of this study is to evaluate blood cadmium levels (BCLs) in Chinese adults and explore whether blood cadmium is associated with diabetes or obesity. This study included 5544 adults from a cross-sectional SPECT-China study. BCL and blood lead level (BLL) was measured by atomic absorption spectrometry. Fasting plasma glucose (FPG) was used to define prediabetes and diabetes. Overweight and obesity were defined by body mass index (BMI). The associations of BCL with prediabetes, diabetes, overweight, and obesity were analyzed by multinomial logistic regression analyses. Medians (interquartile range) of BCL were 1.97 μg/L (0.60-3.82) in men and 1.59 μg/L (0.54-3.51) in women. Subjects in low-economic-status areas and urban areas had significantly higher BCL. BCL in current smokers was significantly higher than in current non-smokers. In the adjusted model, a mild positive relationship between BCL and FPG was found. Meanwhile, the prevalence of prediabetes was increased according to the increase in BCL tertiles. Surprisingly, BCL had a negative relationship with prevalence of overweight. In conclusion, BCL in Chinese adults was much higher than in other developed countries and was influenced by gender, smoking, and residential area. BCL was positively related to prediabetes while negatively related to overweight. PMID:27312901

  5. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5.

    PubMed

    Choi, Jang Hyun; Banks, Alexander S; Estall, Jennifer L; Kajimura, Shingo; Boström, Pontus; Laznik, Dina; Ruas, Jorge L; Chalmers, Michael J; Kamenecka, Theodore M; Blüher, Matthias; Griffin, Patrick R; Spiegelman, Bruce M

    2010-07-22

    Obesity induced in mice by high-fat feeding activates the protein kinase Cdk5 (cyclin-dependent kinase 5) in adipose tissues. This results in phosphorylation of the nuclear receptor PPARgamma (peroxisome proliferator-activated receptor gamma), a dominant regulator of adipogenesis and fat cell gene expression, at serine 273. This modification of PPARgamma does not alter its adipogenic capacity, but leads to dysregulation of a large number of genes whose expression is altered in obesity, including a reduction in the expression of the insulin-sensitizing adipokine, adiponectin. The phosphorylation of PPARgamma by Cdk5 is blocked by anti-diabetic PPARgamma ligands, such as rosiglitazone and MRL24. This inhibition works both in vivo and in vitro, and is completely independent of classical receptor transcriptional agonism. Similarly, inhibition of PPARgamma phosphorylation in obese patients by rosiglitazone is very tightly associated with the anti-diabetic effects of this drug. All these findings strongly suggest that Cdk5-mediated phosphorylation of PPARgamma may be involved in the pathogenesis of insulin-resistance, and present an opportunity for development of an improved generation of anti-diabetic drugs through PPARgamma.

  6. Mediterranean diet rich in olive oil and obesity, metabolic syndrome and diabetes mellitus.

    PubMed

    Pérez-Martínez, Pablo; García-Ríos, Antonio; Delgado-Lista, Javier; Pérez-Jiménez, Francisco; López-Miranda, José

    2011-01-01

    After decades of epidemiological, clinical and experimental research, it has become clear that consumption of Mediterranean dietary patterns rich in olive oil has a profound influence on health outcomes, including obesity, metabolic syndrome (MetS) and diabetes mellitus. Traditionally, many beneficial properties associated with this oil have been ascribed to its high oleic acid content. Olive oil, however, is a functional food that, besides having high-monounsaturated (MUFA) content, contains other minor components with biological properties. In this line, phenolic compounds have shown antioxidant and antiinflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Research into the pharmacological properties of the minor components of olive oil is very active and could lead to the formulation of functional food and nutraceuticals. Although more data are mandatory the Mediterranean diet rich in olive oil does not contribute to obesity and appears to be a useful tool in the lifestyle management of the MetS. Moreover there is good scientific support for MUFA diets, especially those based on olive oil, as an alternative approach to low-fat diets for the medical nutritional therapy in diabetes. The objective of this review is to present evidence illustrating the relationship between Mediterranean diet, olive oil and metabolic diseases, including obesity, MetS and diabetes mellitus and to discuss potential mechanisms by which this food can help in disease prevention and treatment.

  7. Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation.

    PubMed

    McPhee, Joseph B; Schertzer, Jonathan D

    2015-12-01

    The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes.

  8. Improvement of diabetes, obesity and hypertension in type 2 diabetic KKA{sup y} mice by bis(allixinato)oxovanadium(IV) complex

    SciTech Connect

    Adachi, Yusuke; Yoshikawa, Yutaka; Yoshida, Jiro; Kodera, Yukihiro . E-mail: kodera_y@wakunaga.co.jp; Katoh, Akira . E-mail: katoh@st.seikei.ac.jp; Takada, Jitsuya . E-mail: takada@hl.rri.kyoto-u.ac.jp; Sakurai, Hiromu . E-mail: sakurai@mb.kyoto-phu.ac.jp

    2006-07-07

    Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx){sub 2}) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx){sub 2} was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx){sub 2} was examined in obesity-linked type 2 diabetic KKA{sup y} mice. Treatment of VO(alx){sub 2} for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA{sup y} mice; however, it had no effect on hypoadiponectinemia. VO(alx){sub 2} also improved hyperleptinemia, following attenuation of obesity in KKA{sup y} mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx){sub 2} is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal.

  9. The incretin effect in obese adolescents with and without type 2 diabetes: impaired or intact?

    PubMed

    Aulinger, Benedikt A; Vahl, Torsten P; Prigeon, Ron L; D'Alessio, David A; Elder, Deborah A

    2016-05-01

    The incretin effect reflects the actions of enteral stimuli to promote prandial insulin secretion. Impairment of this measure has been proposed as an early marker of β-cell dysfunction and described in T2D, IGT, and even obesity without IGT. We sought to determine the effects of obesity and diabetes on the incretin effect in young subjects with short exposures to metabolic abnormalities and a few other confounding medical conditions. Subjects with T2D (n = 10; 18.0 ± 0.4 yr) or NGT, either obese (n = 11; 17.7 ± 0.4 yr) or lean (n = 8; 26.5 ± 2.3 yr), had OGTT and iso-iv. The incretin effect was calculated as the difference in insulin secretion during these tests and was decreased ∼50% in both the NGT-Ob and T2D subjects relative to the NGT-Ln group. The T2D group had impaired glucose tolerance and insulin secretion during the OGTT, whereas the lean and obese NGT subjects had comparable glucose excursions and β-cell function. During the iso-iv test, the NGT-Ob subjects had significantly greater insulin secretion than the NGT-Ln and T2D groups. These findings demonstrate that in young subjects with early, well-controlled T2D the incretin effect is reduced, similar to what has been described in diabetic adults. The lower incretin effect calculated for the obese subjects with NGT is driven by a disproportionately greater insulin response to iv glucose and does not affect postprandial glucose regulation. These findings confirm that the incretin effect is an early marker of impaired insulin secretion in persons with abnormal glucose tolerance but suggest that in obese subjects with NGT the incretin effect calculation can be confounded by exaggerated insulin secretion to iv glucose.

  10. Survey of Hypertension, Diabetes and Obesity in Three Nigerian Urban Slums

    PubMed Central

    PHEABIAN AKINWALE, Olaoluwa; JOHN OYEFARA, Lekan; ADEJOH, Pius; ADEWALE ADENEYE, Adejuwon; KAZEEM ADENEYE, Adeniyi; ADESOLA MUSA, Zaidat; SOLOMON OYEDEJI, Kolawole; AYOBAMI SULYMAN, Medinat

    2013-01-01

    Abstract Background Non-communicable diseases (NCDs) exist in slums as the inhabitants adopt an urbanized lifestyle which places them at a higher risk for. Lack of knowledge about the morbidity, complications and the method of control contributes to a large percentage of undetected and untreated cases. Methods This cross-sectional survey polled 2,434 respondents from Ijora Oloye, Ajegunle and Makoko, three urban slums in Lagos metropolis, southwestern Nigeria between June 2010 and October 2012. We investigated the prevalence of hypertension, diabetes and obesity. Respondents signed consent forms and their health conditions were documented based on self-reported history of diabetes, hypertension and family history using a semi-structured questionnaire. Diagnostic tests; weight and height for body mass index, blood glucose, and blood pressure were performed. Results More than one quarter of the participants were suffering from hypertension and only half of this were diagnosed earlier, while a further few were already on treatment. Therefore on screening, it had been possible to diagnose over three hundred more respondents, who were not previously aware of their health status. The respondents’ BMI showed that more than half of them were either overweight or obese and are at risk for diabetes, while 3.3% were confirmed as being diabetic, with their sugar levels greater than the normal range. Conclusion This study therefore revealed the near absence of screening programs for chronic diseases such as hypertension, diabetes and obesity in these urban slums. This was further confirmed by the detection of new and undiagnosed cases of hypertension in about one quarter of the respondents. PMID:26060658

  11. Effect of Maternal Age at Childbirth on Obesity in Postmenopausal Women: A Nationwide Population-Based Study in Korea.

    PubMed

    We, Ji-Sun; Han, Kyungdo; Kwon, Hyuk-Sang; Kil, Kicheol

    2016-05-01

    The object of this study was to assess the obesity in postmenopausal women, according to age at childbirth.We analyzed the association between age at first childbirth, age at last childbirth, parity, and subject obesity status (general obesity; BMI >25 kg/m, nongeneral obesity; BMI ≤25 kg/m, abdominal obesity; waist circumference >85 cm, nonabdominal obesity; waist circumference ≤85 cm), using data from a nationwide population-based survey, the 2010 to 2012 Korean National Health and Nutrition Examination Survey. Data from a total of 4382 postmenopausal women were analyzed using multivariate regression analysis with complex survey design sampling. And, the subjects were subdivided into groups according to obesity or not. Age, smoking, alcohol consumption, exercise, education, income level, number of pregnancies, oral contraceptive uses, breast feeding experience were adjusted as the confounders.The prevalence of general obesity among Korean postmenopausal women was 37.08%. Women with general obesity and abdominal obesity were significantly younger at first childbirth compared with women with nongeneral obesity and no abdominal obesity (23.89 ± 0.1 vs. 23.22 ± 0.1, P <0.001). Age at first childbirth was inversely associated with obesity, while age at last childbirth was not associated with obesity or abdominal obesity. Women with a higher number of pregnancies were also more likely to have obesity and abdominal obesity. Age at first childbirth remained significantly associated with obesity, after adjusting for confounding factors.Obesity in postmenopausal women is associated with first childbirth at a young age, and higher parity. Further research is needed to clarify the association between obesity and reproductive characteristics. PMID:27175656

  12. Being overweight and obese: Black children ages 2-5 years.

    PubMed

    Hudson, Cindy E

    2008-01-01

    Obesity in children is a significant public health concern. The prevalence of obesity in Black preschoolers (ages 2-5 years) is slightly higher than in whites. However, by age 6, Black children experience higher obesity prevalence. The consequences to health throughout childhood and into adulthood have both medical and economic cost to individuals and society. Factors associated with obesity in preschool children are lifestyle behaviors such as diet, level of activity, culture, environment, and parental perceptions. Programs should target young Black children and their families to reduce the incidence of obesity and promoting healthy behaviors could aid in eliminating health disparities and improving quality of life. Nurses need to provide comprehensive culturally appropriate strategies at community and individual/family levels to prevent overweight and obesity in children.

  13. Diagnostic Value of Cell-free Circulating MicroRNAs for Obesity and Type 2 Diabetes: A Meta-analysis

    PubMed Central

    Villard, Audrey; Marchand, Lucien; Thivolet, Charles; Rome, Sophie

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder worldwide. Because of population aging and increasing trends toward obesity and sedentary lifestyles, the number of affected individuals is increasing at worrisome rates. While both environmental and genetic factors are known to contribute to the development of T2DM, continuous research is needed to identify specific biomarkers that could aid both in prevention of the disease and development of newer therapeutic options. Circulating miRNAs are considered as potential biomarkers because they are stable and resistant to degradation by blood RNAses and are modified under different pathophysiological conditions. In this study we carried out a systematic electronic search on PubMed to retrieve all articles that have investigated circulating miRNAs for diagnosing obesity andT2DM in human. We also included lifestyle intervention studies known to be highly effective in delaying onset of diabetes, and studies analyzing the effect of bariatric surgery and anti-diabetic treatment. A total of 26 studies were enrolled in the global meta-analysis. Candidate miRNAs were defined as those reported in at least 2 studies with same direction of differential expression. Ten miRNAs altered in blood of patients suffering fromT2DM were identified (increased: miR-320a, miR-142-3p, miR-222, miR-29a, miR-27a, miR-375; decreased: miR-197, miR-20b, miR-17, miR-652) and 7 miRNAs in blood of obese subjects were identified (increased: miR-142-3p, miR-140-5p, miR-222; decreased:miR-21-5p, miR-221-3p, miR-125-5p, mir-103-5p). Both obese and T2DM patients had elevated concentrations of miR-142-3p and miR-222. MiRNAs target genes were predicted and their cellular functions are discussed in relation with the pathologies. Although a significant number of studies were taken into account in this review, we found a strong discrepancy between miRNA detection and quantification indicating that many of pre-analytical variables have yet to

  14. The prevalences of impaired fasting glucose and diabetes mellitus in working age men of North China: Anshan Worker Health Survey.

    PubMed

    Liu, Lei; Zhou, Chuang; Du, Hang; Zhang, Kai; Huang, Desheng; Wu, Jingyang

    2014-01-01

    To investigate the prevalence of impaired fasting glucose (IFG) and total diabetes mellitus (DM) including known diabetes and newly diagnosed diabetes in working age men of North China. A cross-section study was conducted at health medical center of Ansteel Group Hospital in Anshan city of China. 37,345 males between 20-60 years of age were recruited in this study. Age-standardized prevalence of IFG and total DM in these working age men were 25.3% and 8.4%, respectively. The prevalence of IFG and total DM increased, as the age progressed. After multinomial logit analysis, age, systolic blood pressure, drinking, smoking, overweight and obesity, total cholesterol, triglycerides, serum creatinine and blood urea nitrogen were independent risk factors for both IFG and DM. The prevalence rate of IFG in Anshan male workers was higher compared with mainland China overall. Diabetes-related education and popularization of DM prevention programs should be actively carried out with age increasing. PMID:24824525

  15. Age, race, diabetes, blood pressure, and mortality among hemodialysis patients.

    PubMed

    Myers, Orrin B; Adams, Christopher; Rohrscheib, Mark R; Servilla, Karen S; Miskulin, Dana; Bedrick, Edward J; Zager, Philip G

    2010-11-01

    Observational studies involving hemodialysis patients suggest a U-shaped relationship between BP and mortality, but the majority of these studies followed large, heterogeneous cohorts. To examine whether age, race, and diabetes status affect the association between systolic BP (SBP; predialysis) and mortality, we studied a cohort of 16,283 incident hemodialysis patients. We constructed a series of multivariate proportional hazards models, adding age and BP to the analyses as cubic polynomial splines to model potential nonlinear relationships with mortality. Overall, low SBP associated with increased mortality, and the association was more pronounced among older patients and those with diabetes. Higher SBP associated with increased mortality among younger patients, regardless of race or diabetes status. We observed a survival advantage for black patients primarily among older patients. Diabetes associated with increased mortality mainly among older patients with low BP. In conclusion, the design of randomized clinical trials to identify optimal BP targets for patients with ESRD should take age and diabetes status into consideration.

  16. Ubc13 haploinsufficiency protects against age-related insulin resistance and high-fat diet-induced obesity

    PubMed Central

    Joo, Erina; Fukushima, Toru; Harada, Norio; Reed, John C.; Matsuzawa, Shu-ichi; Inagaki, Nobuya

    2016-01-01

    Obesity is associated with low-grade inflammation that leads to insulin resistance and type 2 diabetes via Toll-like Receptor (TLR) and TNF-family cytokine receptor (TNFR) signaling pathways. Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical K63-linked polyubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in TLR and TNFR pathways. However, the relationship between Ubc13 and metabolic disease remains unclear. In this study, we investigated the role of Ubc13 in insulin resistance and high-fat diet (HFD)-induced obesity. We compared wild-type (WT) and Ubc13 haploinsufficient (ubc13+/−) mice under normal diet (ND) and HFD, since homozygous knockout mice (ubc13−/−) are embryonic lethal. Male and female ubc13+/− mice were protected against age-related insulin resistance under ND and HFD compared to WT mice. Interestingly, only female ubc13+/− mice were protected against HFD-induced obesity and hepatic steatosis. Moreover, only female HFD-fed ubc13+/− mice showed lower expression of inflammatory cytokines that was secondary to reduction in weight gain not present in the other groups. In summary, our results indicate that suppression of Ubc13 activity may play a metabolic role independent of its inflammatory function. Thus, Ubc13 could represent a therapeutic target for insulin resistance, diet-induced obesity, and associated metabolic dysfunctions. PMID:27796312

  17. Obesity and metabolic surgery in type 1 diabetes mellitus.

    PubMed

    Raab, Heike; Weiner, R A; Frenken, M; Rett, K; Weiner, S

    2013-03-01

    Introducción: La cirugía de la obesidad es un método eficaz para el tratamiento de la obesidad y la diabetes mellitus tipo 2. Este tipo de diabetes puede se resuelve por completo en el 78,1% de los pacientes diabéticos y mejora en el 86,6% de los pacientes diabéticos. Sin embargo, poco se sabe acerca de la cirugía bariátrica en la diabetes mellitus tipo 1. Métodos: Presentamos 6 pacientes mujeres obesas con diabetes mellitus tipo 1 que se sometieron a cirugía bariátrica. Dos de ellas fueron sometidas a un bypass gástrico en-Y-Roux (BPGYR), una se le realizó una gastrectomía en manga y a las tres restantes una derivación biliopancreática con-switch duodenal (DBP-SD). Resultados: Nuestros resultados mostraron una reducción de peso notable, así como una mejora en el control de la glucosa en sangre y el requerimiento de insulina en los años de seguimiento después de la cirugía. El IMC prequirúrgico de las 6 pacientes osciló entre 37,3-46,0 kg/m2 y mejoró a 25,8-29,0 kg/m2 un año después de la cirugía. La HbA1c disminuyó de 6,7-9,8% antes de la cirugía a 5,7-8,5% un año después de la cirugía. El requerimiento diario de insulina se redujo de 62-150 UI/día antes de la cirugía a 15-54 UI /día al cabo de un año. Conclusión: Los resultados son impresionantes y muestran una mejora en la sensibilidad a la insulina tras una cirugía de la obesidad. No obstante, un control óptimo de la glucosa de sangre sigue siendo muy importante en la terapia de la diabetes mellitus tipo 1 para evitarcomplicaciones a largo plazo.

  18. Associations between sleep loss and increased risk of obesity and diabetes

    PubMed Central

    Knutson, Kristen L.; Van Cauter, Eve

    2015-01-01

    During the past few decades, sleep curtailment has become a very common behavior in industrialized countries. This trend for shorter sleep duration has developed over the same time period as the dramatic increase in the prevalence of obesity and diabetes. There is rapidly accumulating evidence to indicate that chronic partial sleep loss may increase the risk of obesity and diabetes. Laboratory studies in healthy volunteers have shown that experimental sleep restriction is associated with an adverse impact on glucose homeostasis. Insulin sensitivity decreases rapidly and markedly without adequate compensation in beta cell function, resulting in an elevated risk of diabetes. Prospective epidemiologic studies in both children and adults are consistent with a causative role of short sleep in the increased risk of diabetes. Sleep curtailment is also associated with a dysregulation of the neuroendocrine control of appetite, with a reduction of the satiety factor leptin and an increase in the hunger-promoting hormone ghrelin. Thus, sleep loss may alter the ability of leptin and ghrelin to accurately signal caloric need, acting in concert to produce an internal misperception of insufficient energy availability. The adverse impact of sleep deprivation on appetite regulation is likely to be driven by increased activity in neuronal populations expressing the excitatory peptides orexins that promote both waling and feeding. Consistent with the laboratory evidence, multiple epidemiologic studies have shown an association between short sleep and higher body mass index after controlling for a variety of possible confounders. PMID:18591489

  19. Relationship of autonomic imbalance and circadian disruption with obesity and type 2 diabetes in resistant hypertensive patients

    PubMed Central

    2011-01-01

    Background Hypertension, diabetes and obesity are not isolated findings, but a series of interacting interactive physiologic derangements. Taking into account genetic background and lifestyle behavior, AI (autonomic imbalance) could be a common root for RHTN (resistant hypertension) or RHTN plus type 2 diabetes (T2D) comorbidity development. Moreover, circadian disruption can lead to metabolic and vasomotor impairments such as obesity, insulin resistance and resistant hypertension. In order to better understand the triggered emergence of obesity and T2D comorbidity in resistant hypertension, we investigated the pattern of autonomic activity in the circadian rhythm in RHTN with and without type 2 diabetes (T2D), and its relationship with serum adiponectin concentration. Methods Twenty five RHTN patients (15 non-T2D and 10 T2D, 15 males, 10 females; age range 34 to 70 years) were evaluated using the following parameters: BMI (body mass index), biochemical analysis, serum adiponectinemia, echocardiogram and ambulatory electrocardiograph heart rate variability (HRV) in time and frequency domains stratified into three periods: 24 hour, day time and night time. Results Both groups demonstrated similar characteristics despite of the laboratory analysis concerning T2D like fasting glucose, HbA1c levels and hypertriglyceridemia. Both groups also revealed disruption of the circadian rhythm: inverted sympathetic and parasympathetic tones during day (parasympathetic > sympathetic tone) and night periods (sympathetic > parasympathetic tone). T2D group had increased BMI and serum triglyceride levels (mean 33.7 ± 4.0 vs 26.6 ± 3.7 kg/m2 - p = 0.00; 254.8 ± 226.4 vs 108.6 ± 48.7 mg/dL - p = 0.04), lower levels of adiponectin (6729.7 ± 3381.5 vs 10911.5 ± 5554.0 ng/mL - p = 0.04) and greater autonomic imbalance evaluated by HRV parameters in time domain compared to non-T2D RHTN patients. Total patients had HRV correlated positively with serum adiponectin (r = 0.37 [95% CI -0

  20. Protective Effect of Gymnema sylvestre Ethanol Extract on High Fat Diet-induced Obese Diabetic Wistar Rats.

    PubMed

    Kumar, V; Bhandari, Uma; Tripathi, C D; Khanna, Geetika

    2014-07-01

    Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg) via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate), serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose), cardiomyocyte apoptosis (cardiac caspase-3, Na(+)/K(+) ATPase activity and DNA fragmentation) organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o.) for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na(+)/K(+) ATPase activity and DNA laddering, visceral fat pad and organ's weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus.

  1. Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients

    PubMed Central

    Kirchner, Henriette; Sinha, Indranil; Gao, Hui; Ruby, Maxwell A.; Schönke, Milena; Lindvall, Jessica M.; Barrès, Romain; Krook, Anna; Näslund, Erik; Dahlman-Wright, Karin; Zierath, Juleen R.

    2016-01-01

    Objective Epigenetic modifications contribute to the etiology of type 2 diabetes. Method We performed genome-wide methylome and transcriptome analysis in liver from severely obese men with or without type 2 diabetes and non-obese men to discover aberrant pathways underlying the development of insulin resistance. Results were validated by pyrosequencing. Result We identified hypomethylation of genes involved in hepatic glycolysis and insulin resistance, concomitant with increased mRNA expression and protein levels. Pyrosequencing revealed the CpG-site within ATF-motifs was hypomethylated in four of these genes in liver of severely obese non-diabetic and type 2 diabetic patients, suggesting epigenetic regulation of transcription by altered ATF-DNA binding. Conclusion Severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome and transcriptome, with hypomethylation of several genes controlling glucose metabolism within the ATF-motif regulatory site. Obesity appears to shift the epigenetic program of the liver towards increased glycolysis and lipogenesis, which may exacerbate the development of insulin resistance. PMID:26977391

  2. Prevalence and determinants of overweight, obesity, and type 2 diabetes mellitus in adults in Malaysia.

    PubMed

    Jan Mohamed, Hamid Jan B; Yap, Roseline Wai Kuan; Loy, See Ling; Norris, Shane A; Biesma, Regien; Aagaard-Hansen, Jens

    2015-03-01

    This systematic review aimed to examine trends in overweight, obesity, and type 2 diabetes mellitus (T2DM) among Malaysian adults, and to identify its underlying determinants. A review of studies published between 2000 and 2012 on overweight, obesity, and T2DM was conducted. The Cochrane library of systematic reviews, MEDLINE, EMBASE, Biosis, Scopus, and MyJurnal digital database were searched. According to national studies, the prevalence of overweight increased from 26.7% in 2003 to 29.4% in 2011; obesity prevalence increased from 12.2% in 2003 to 15.1% in 2011, and T2DM prevalence was reported as 11.6% in 2006 and 15.2% in 2011. Distal determinants of increased risk of overweight, obesity, and T2DM were as follows: female, Malay/Indian ethnicity, and low educational level. The limited number of studies on proximal determinants of these noncommunicable diseases (NCDs) indicated that an unhealthy diet was associated with increased risk, whereas smoking was associated with decreased risk. However, more studies on the proximal determinants of overweight, obesity, and T2DM within the Malaysian context are needed. Overall, our findings provide insights for designing both future investigative studies and strategies to control and prevent these NCDs in Malaysia.

  3. Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity

    PubMed Central

    Oh, Chang-Myung; Park, Sangkyu

    2016-01-01

    Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine that has various functions in both neuronal and non-neuronal systems. In the central nervous system, 5-HT regulates mood and feeding behaviors as a neurotransmitter. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. Unfortunately, some drugs were withdrawn due to the development of unwanted peripheral side effects, such as valvular heart disease and pulmonary hypertension. Recent studies revealed that peripheral 5-HT plays an important role in metabolic regulation in peripheral tissues, where it suppresses adaptive thermogenesis in brown adipose tissue. Inhibition of 5-HT synthesis reduced the weight gain and improved the metabolic dysfunction in a diet-induced obesity mouse model. Genome-wide association studies also revealed genetic associations between the serotonergic system and obesity. Several genetic polymorphisms in tryptophan hydroxylase and 5-HT receptors were shown to have strong associations with obesity. These results support the clinical significance of the peripheral serotonergic system as a therapeutic target for obesity and diabetes. PMID:27126880

  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. Prevalence and determinants of overweight, obesity, and type 2 diabetes mellitus in adults in Malaysia.

    PubMed

    Jan Mohamed, Hamid Jan B; Yap, Roseline Wai Kuan; Loy, See Ling; Norris, Shane A; Biesma, Regien; Aagaard-Hansen, Jens

    2015-03-01

    This systematic review aimed to examine trends in overweight, obesity, and type 2 diabetes mellitus (T2DM) among Malaysian adults, and to identify its underlying determinants. A review of studies published between 2000 and 2012 on overweight, obesity, and T2DM was conducted. The Cochrane library of systematic reviews, MEDLINE, EMBASE, Biosis, Scopus, and MyJurnal digital database were searched. According to national studies, the prevalence of overweight increased from 26.7% in 2003 to 29.4% in 2011; obesity prevalence increased from 12.2% in 2003 to 15.1% in 2011, and T2DM prevalence was reported as 11.6% in 2006 and 15.2% in 2011. Distal determinants of increased risk of overweight, obesity, and T2DM were as follows: female, Malay/Indian ethnicity, and low educational level. The limited number of studies on proximal determinants of these noncommunicable diseases (NCDs) indicated that an unhealthy diet was associated with increased risk, whereas smoking was associated with decreased risk. However, more studies on the proximal determinants of overweight, obesity, and T2DM within the Malaysian context are needed. Overall, our findings provide insights for designing both future investigative studies and strategies to control and prevent these NCDs in Malaysia. PMID:25524952

  6. Obesity

    MedlinePlus

    Morbid obesity; Fat - obese ... is because the body stores unused calories as fat. Obesity can be caused by: Eating more food ... use your BMI to estimate how much body fat you have. Your waist measurement is another way ...

  7. Lysozyme enhances renal excretion of advanced glycation endproducts in vivo and suppresses adverse age-mediated cellular effects in vitro: a potential AGE sequestration therapy for diabetic nephropathy?

    PubMed Central

    Zheng, F.; Cai, W.; Mitsuhashi, T.; Vlassara, H.

    2001-01-01

    BACKGROUND: Lysozyme (LZ), a host-defense protein, contains an 18 amino-acid domain with high affinity binding for sugar-derived proteins or lipids, called advanced glycation endproducts (AGE), that are implicated in diabetes- and age-dependent complications (DC). MATERIALS AND METHODS: A) The effects of LZ on AGE- removal were tested in vivo. LZ was injected (200 ug/day, i.p., X2 weeks) in non-obese diabetic (NOD), db/db (+/+) mice, and non-diabetic, AGE-infused Sprague-Dawley rats. B) LZ: AGE interactions with macrophage-like T1B-183 cells (Mf) and mesangial cells (MC) were tested in vitro. RESULTS: A) In NOD mice, LZ reduced the elevated basal serum AGE (sAGE) (p < 0.05), enhanced urinary AGE (uAGE) excretion by approximately 2-fold (p < 0.01), while it reduced albuminuria (UA), p < 0.005. In db/db mice, LZ infusion also reduced the elevated sAGE (p < 0.05), doubled uAGE excretion (p < 0.05), and decreased UA (p < 0.01). In addition, LZ maintained normal sAGE in normal rats infused with AGE-BSA, as it doubled the urinary AGE (uAGE) clearance (p < 0.01). B) LZ stimulated the uptake and degradation of (125) I-labeled AGE-BSA and (25) I-human serum AGE by Mf, while suppressing AGE-induced TNFalpha and IGF-I production. In MC, LZ suppressed the AGE-promoted PDGF-B, alpha1 type IV collagen, and tenascin mRNA levels, and restored the AGE-suppressed expression and activity of MMP-9, but not MMP-2. CONCLUSION: LZ may act to: a) accelerate renal in-vivo AGE clearance, b) suppress macrophage and mesangial cell- specific gene activation in vitro, and c) improve albuminuria due to diabetes. These data suggest that LZ by sequestering AGEs may protect against diabetic renal damage. PMID:11788787

  8. Perceptions of School Nurses regarding Obesity in School-Age Children

    ERIC Educational Resources Information Center

    Moyers, Pamela; Bugle, Linda; Jackson, Elaine

    2005-01-01

    Obesity is epidemic in the nation's school-age population with African American and Hispanic children and adolescents specifically at risk. School nurses at elementary and middle public schools in the Missouri 8th Congressional District were surveyed regarding their perceptions of childhood obesity. School nurses supported preventive interventions…

  9. Prevalence of Obesity and Overweight Among School Children Aged 8-18 Years in Rajkot, Gujarat.

    PubMed

    Chudasama, Rajesh K; Eshwar, Tkm; Eshwar, Subhasini T; Thakkar, Dhara

    2016-08-01

    A total of 1496 school children aged 8-18 years (79.1% boys) participated in this study. Prevalence of obesity and overweight was estimated by using three different growth standards. Revised IAP 2015 growth standards detected more obese and overweight children than WHO 2007 and IOTF standards. PMID:27395837

  10. Genetic Evidence for a Causal Role of Obesity in Diabetic Kidney Disease.

    PubMed

    Todd, Jennifer N; Dahlström, Emma H; Salem, Rany M; Sandholm, Niina; Forsblom, Carol; McKnight, Amy J; Maxwell, Alexander P; Brennan, Eoin; Sadlier, Denise; Godson, Catherine; Groop, Per-Henrik; Hirschhorn, Joel N; Florez, Jose C

    2015-12-01

    Obesity has been posited as an independent risk factor for diabetic kidney disease (DKD), but establishing causality from observational data is problematic. We aimed to test whether obesity is causally related to DKD using Mendelian randomization, which exploits the random assortment of genes during meiosis. In 6,049 subjects with type 1 diabetes, we used a weighted genetic risk score (GRS) comprised of 32 validated BMI loci as an instrument to test the relationship of BMI with macroalbuminuria, end-stage renal disease (ESRD), or DKD defined as presence of macroalbuminuria or ESRD. We compared these results with cross-sectional and longitudinal observational associations. Longitudinal analysis demonstrated a U-shaped relationship of BMI with development of macroalbuminuria, ESRD, or DKD over time. Cross-sectional observational analysis showed no association with overall DKD, higher odds of macroalbuminuria (for every 1 kg/m(2) higher BMI, odds ratio [OR] 1.05, 95% CI 1.03-1.07, P < 0.001), and lower odds of ESRD (OR 0.95, 95% CI 0.93-0.97, P < 0.001). Mendelian randomization analysis showed a 1 kg/m(2) higher BMI conferring an increased risk in macroalbuminuria (OR 1.28, 95% CI 1.11-1.45, P = 0.001), ESRD (OR 1.43, 95% CI 1.20-1.72, P < 0.001), and DKD (OR 1.33, 95% CI 1.17-1.51, P < 0.001). Our results provide genetic evidence for a causal link between obesity and DKD in type 1 diabetes. As obesity prevalence rises, this finding predicts an increase in DKD prevalence unless intervention should occur.

  11. Role of Environmental Chemicals in Diabetes and Obesity: A National Toxicology Program Workshop Review

    PubMed Central

    Heindel, Jerrold J.; Bucher, John R.; Gallo, Michael A.

    2012-01-01

    Background: There has been increasing interest in the concept that exposures to environmental chemicals may be contributing factors to the epidemics of diabetes and obesity. On 11–13 January 2011, the National Institute of Environmental Health Sciences (NIEHS) Division of the National Toxicology Program (NTP) organized a workshop to evaluate the current state of the science on these topics of increasing public health concern. Objective: The main objective of the workshop was to develop recommendations for a research agenda after completing a critical analysis of the literature for humans and experimental animals exposed to certain environmental chemicals. The environmental exposures considered at the workshop were arsenic, persistent organic pollutants, maternal smoking/nicotine, organotins, phthalates, bisphenol A, and pesticides. High-throughput screening data from Toxicology in the 21st Century (Tox21) were also considered as a way to evaluate potential cellular pathways and generate -hypotheses for testing which and how certain chemicals might perturb biological processes related to diabetes and obesity. Conclusions: Overall, the review of the existing literature identified linkages between several of the environmental exposures and type 2 diabetes. There was also support for the “developmental obesogen” hypothesis, which suggests that chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes or the development of neural circuits that regulate feeding behavior. The effects may be most apparent when the developmental exposure is combined with consumption of a high-calorie, high-carbohydrate, or high-fat diet later in life. Research on environmental chemical exposures and type 1 diabetes was very limited. This lack of research was considered a critical data gap. In this workshop review, we outline the major themes that emerged from the workshop and discuss activities that NIEHS/NTP is undertaking to address research

  12. Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

    SciTech Connect

    Yasuda-Yamahara, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi; Koya, Daisuke; Haneda, Masakzu; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

    2015-09-18

    Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.

  13. 5-HT Obesity Medication Efficacy via POMC Activation is Maintained During Aging

    PubMed Central

    Burke, Luke K.; Doslikova, Barbora; D'Agostino, Giuseppe; Garfield, Alastair S.; Farooq, Gala; Burdakov, Denis; Low, Malcolm J.; Rubinstein, Marcelo; Evans, Mark L.; Billups, Brian

    2014-01-01

    The phenomenon commonly described as the middle-age spread is the result of elevated adiposity accumulation throughout adulthood until late middle-age. It is a clinical imperative to gain a greater understanding of the underpinnings of age-dependent obesity and, in turn, how these mechanisms may impact the efficacy of obesity treatments. In particular, both obesity and aging are associated with rewiring of a principal brain pathway modulating energy homeostasis, promoting reduced activity of satiety pro-opiomelanocortin (POMC) neurons within the arcuate nucleus of the hypothalamus (ARC). Using a selective ARC-deficient POMC mouse line, here we report that former obesity medications augmenting endogenous 5-hydroxytryptamine (5-HT) activity d-fenfluramine and sibutramine require ARC POMC neurons to elicit therapeutic appetite-suppressive effects. We next investigated whether age-related diminished ARC POMC activity therefore impacts the potency of 5-HT obesity pharmacotherapies, lorcaserin, d-fenfluramine, and sibutramine and report that all compounds reduced food intake to a comparable extent in both chow-fed young lean (3–5 months old) and middle-aged obese (12–14 months old) male and female mice. We provide a mechanism through which 5-HT anorectic potency is maintained with age, via preserved 5-HT–POMC appetitive anatomical machinery. Specifically, the abundance and signaling of the primary 5-HT receptor influencing appetite via POMC activation, the 5-HT2CR, is not perturbed with age. These data reveal that although 5-HT obesity medications require ARC POMC neurons to achieve appetitive effects, the anorectic efficacy is maintained with aging, findings of clinical significance to the global aging obese population. PMID:25051442

  14. Brd2 disruption in mice causes severe obesity without Type 2 diabetes.

    PubMed

    Wang, Fangnian; Liu, Hongsheng; Blanton, Wanda P; Belkina, Anna; Lebrasseur, Nathan K; Denis, Gerald V

    2010-01-01

    Certain human subpopulations are metabolically healthy but obese, or metabolically obese but normal weight; such mutations uncouple obesity from glucose intolerance, revealing pathways implicated in Type 2 diabetes. Current searches for relevant genes consume significant effort. We have reported previously a novel double bromodomain protein called Brd2, which is a transcriptional co-activator/co-repressor with SWI/SNF (switch mating type/sucrose non-fermenting)-like functions that regulates chromatin. In the present study, we show that wholebody disruption of Brd2, an unusual MHC gene, causes lifelong severe obesity in mice with pancreatic islet expansion, hyperinsulinaemia, hepatosteatosis and elevated pro-inflammatory cytokines, but, surprisingly, enhanced glucose tolerance, elevated adiponectin, increased weight of brown adipose tissue, heat production and expression of mitochondrial uncoupling proteins in brown adipose tissue, reduced macrophage infiltration in white adipose tissue, and lowered blood glucose, leading to an improved metabolic profile and avoiding eventual Type 2 diabetes. Brd2 is highly expressed in pancreatic beta-cells, where it normally inhibits beta-cell mitosis and insulin transcription. In 3T3-L1 pre-adipocytes, Brd2 normally co-represses PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) and inhibits adipogenesis. Brd2 knockdown protects 3T3-L1 adipocytes from TNF-alpha (tumour necrosis factor-alpha)-induced insulin resistance, thereby decoupling inflammation from insulin resistance. Thus hypomorphic Brd2 shifts energy balance toward storage without causing glucose intolerance and may provide a novel model for obese metabolically healthy humans. PMID:19883376

  15. Comparison of renal calcium concentration in obese, lean, diabetic, and non-diabetic Zucker rats fed a magnesium-deficient fructose diet.

    PubMed

    Koh, E T; Min, K W; Scholfield, D J; Sarkarcadeh, A

    1991-01-01

    In order to determine the effects of hypoinsulinaemia or hyperinsulinaemia on nephrocalcinosis induced by the interaction between fructose and magnesium (Mg) deficiency, we compared kidney calcification in obese versus lean, and non-diabetic versus diabetic female Zucker rats fed a magnesium-deficient fructose diet. One half of the obese and lean animals, respectively, was injected with streptozotocin to produce diabetes, and the other half was injected with citrate buffer alone. Diabetic, non-diabetic, obese, and lean animals were divided into two dietary groups, consisting of high starch or high fructose without added Mg. After a four week period, 24 hour urine was collected for urinary output, protein, oxalate, citrate, MG, and calcium (Ca) measurements. The animals were then decapitated, and blood was collected for glucose, Mg, and Ca determinations, and kidneys were removed to determine their Mg and Ca contents. All fructose-fed animals exhibited significantly more kidney Ca then the starch-fed animals. Lean non-diabetic rats fed fructose showed the greatest kidney Ca along with the greatest urinary protein excretion among all experimental groups. The significant finding in the present study is that diabetes or obesity reduced nephrocalcinosis regardless of the insulin status of the rats. Diuresis and hypercitraturia in diabetic and/or obese animals may cause a reduction in nephrocalcinosis induced by the interaction between fructose and magnesium deficiency. Hyperproteinuria (uromucoid) in combination with hypercalciuria and hypomagnesuria may be responsible for greater nephrocalcinosis in the fructose than the starch group. The possible mechanisms for this interaction on nephrocalcinosis have been discussed.

  16. Ambulatory Blood Pressure Monitoring in Lean, Obese and Diabetic Children and Adolescents

    PubMed Central

    Shikha, Deep; Singla, Montish; Walia, Rachna; Potter, Natia; Umpaichitra, Vatcharapan; Mercado, Arlene; Winer, Nathaniel

    2015-01-01

    Aim To determine if children and adolescents who have obesity (Ob) or type 2 diabetes (T2DM) of relatively short duration have impaired cardiovascular function compared with lean subjects using 24-hour ambulatory blood pressure as a surrogate measure of evaluation. Methods We enrolled 100 African-Caribbean subjects (45 males/55 females), mean ages 14.4-15.2 years (range 11.8-18.5 years) and Tanner stage 4.2-4.8. Mean BMI for the Ob (n = 40), T2DM (n = 39) and lean (n = 21) groups were 40.3, 34.2 and 20.8, respectively (p < 0.01, Ob and T2DM vs. lean). Mean hemoglobin A1c in lean and Ob was 5.4 and 5.5% compared to 8.8% in T2DM (p < 0.001, T2DM vs. lean and Ob). Ambulatory blood pressure was recorded every 20 min over 24 h using Spacelabs 70207. Results Mean 24-hour, daytime and nighttime systolic blood pressure was significantly higher in Ob and T2DM compared with lean subjects (mean 24-hour 117 and 120 vs. 109 mm Hg; daytime 121 and 123 vs. 113 mm Hg; and nighttime 109 and 115 vs. 101 mm Hg; p < 0.01 for all time periods). The nocturnal systolic dip in Ob and T2DM did not differ from that of lean, whereas nocturnal diastolic dip decreased significantly in Ob and T2DM compared to lean (11.5 and 10.4 vs. 20.6 mm Hg; p < 0.01). Mean pulse pressure was significantly increased in the Ob and T2DM groups compared to lean subjects (51 and 54 vs. 45 mm Hg; p < 0.01). Conclusion Adolescent Ob and T2DM groups share adverse risk factors, which may be harbingers of adult cardiovascular events. PMID:26195970

  17. Repeated electroacupuncture in obese Zucker diabetic fatty rats: adiponectin and leptin in serum and adipose tissue.

    PubMed

    Peplow, Philip V

    2015-04-01

    Fasted, male, obese, Zucker, diabetic fatty rats aged 10-16 weeks were anesthetized with 1% halothane in nitrous oxide-oxygen (3:1) on alternate weekdays over 2 weeks. Group 1 (n = 4) did not receive electroacupuncture (controls); Group 2 (n = 4) received electroacupuncture using the Zhongwan and the Guanyuan acupoints; Group 3 (n = 4) received electroacupuncture using the bilateral Zusanli acupoints; Group 4 (n = 6) received neither halothane in nitrous oxide:oxygen nor electroacupuncture. At the end of study, animals were injected with sodium pentobarbitone (60 mg/mL, i.p.), and blood and white adipose tissue were collected. Analysis of variance and Duncan's tests showed that the mean leptin in serum was significantly lower and the adiponectin:leptin ratio was significantly higher in Group 2 than in Group 1 (p < 0.05); for Group 4, the serum leptin was significantly higher than it was for Groups 1-3 (p < 0.05), and the adiponectin:leptin ratio was significantly lower than it was for Group 2 (p < 0.05). Similar changes occurred for the leptin levels in the pelvic adipose tissue. In addition, for Group 2, the mean serum insulin: glucose ratio was significantly higher than it was for Group 1 (p < 0.05); for Group 4 the mean serum insulin and insulin: glucose ratio were significantly higher than they were for Groups 1 and 3 (p < 0.05), but not Group 2 (p > 0.05). No significant differences in the serum or the adipose-tissue measurements between Groups 1 and 3 were observed (p > 0.05). PMID:25952122

  18. Repeated electroacupuncture in obese Zucker diabetic fatty rats: adiponectin and leptin in serum and adipose tissue.

    PubMed

    Peplow, Philip V

    2015-04-01

    Fasted, male, obese, Zucker, diabetic fatty rats aged 10-16 weeks were anesthetized with 1% halothane in nitrous oxide-oxygen (3:1) on alternate weekdays over 2 weeks. Group 1 (n = 4) did not receive electroacupuncture (controls); Group 2 (n = 4) received electroacupuncture using the Zhongwan and the Guanyuan acupoints; Group 3 (n = 4) received electroacupuncture using the bilateral Zusanli acupoints; Group 4 (n = 6) received neither halothane in nitrous oxide:oxygen nor electroacupuncture. At the end of study, animals were injected with sodium pentobarbitone (60 mg/mL, i.p.), and blood and white adipose tissue were collected. Analysis of variance and Duncan's tests showed that the mean leptin in serum was significantly lower and the adiponectin:leptin ratio was significantly higher in Group 2 than in Group 1 (p < 0.05); for Group 4, the serum leptin was significantly higher than it was for Groups 1-3 (p < 0.05), and the adiponectin:leptin ratio was significantly lower than it was for Group 2 (p < 0.05). Similar changes occurred for the leptin levels in the pelvic adipose tissue. In addition, for Group 2, the mean serum insulin: glucose ratio was significantly higher than it was for Group 1 (p < 0.05); for Group 4 the mean serum insulin and insulin: glucose ratio were significantly higher than they were for Groups 1 and 3 (p < 0.05), but not Group 2 (p > 0.05). No significant differences in the serum or the adipose-tissue measurements between Groups 1 and 3 were observed (p > 0.05).

  19. [Overweight, obesity, diabetes, and hypertension in endometrial cancer].

    PubMed

    Sanz-Chávez, Tania L N; Vilar-Compte, Diana; de Nicola-Delfín, Luigina; Meneses-García, Abelardo

    2013-01-01

    Introducción: en mujeres posmenopáusicas, el exceso de grasa ha sido asociado con un incremento del riesgo de padecer cáncer de endometrio. El objetivo del estudio fue conocer la frecuencia de sobrepeso, obesidad, diabetes e hipertensión en pacientes con cáncer de endometrio. Métodos: se obtuvieron datos demográficos, clínicos, de laboratorio e histopatológicos de los expedientes electrónicos de las pacientes con diagnóstico de cáncer de endometrio en el periodo comprendido de enero del 2009 a julio del 2011. Posteriormente, se efectuó un análisis descriptivo de la información. Resultados: se incluyó un total de 274 expedientes. El promedio de edad de las pacientes fue de 54 años. El 50.4 % eran posmenopáusicas. En el momento del diagnóstico, 112 casos (48.6 %) se encontraban en etapa clínica I. Del total de pacientes, 104 (37.9 %) presentaron diabetes mellitus, 122 (44.5 %) hipertensión arterial, 194 (72.6 %) sobrepeso u obesidad, y se registraron 24 casos con síndrome metabólico. Conclusiones: para este diagnóstico, los resultados muestran un mayor número de casos de sobrepeso y obesidad en comparación con otros países. Es necesario que se hagan más estudios para evaluar la relación del exceso de grasa como factor de riesgo para el cáncer de endometrio.

  20. Genetic vulnerability to diabetes and obesity: does education offset the risk?

    PubMed

    Liu, S Y; Walter, S; Marden, J; Rehkopf, D H; Kubzansky, L D; Nguyen, T; Glymour, M M

    2015-02-01

    The prevalence of type 2 diabetes (T2D) and obesity has recently increased dramatically. These common diseases are likely to arise from the interaction of multiple genetic, socio-demographic and environmental risk factors. While previous research has found genetic risk and education to be strong predictors of these diseases, few studies to date have examined their joint effects. This study investigates whether education modifies the association between genetic background and risk for type 2 diabetes (T2D) and obesity. Using data from non-Hispanic Whites in the Health and Retirement Study (HRS, n = 8398), we tested whether education modifies genetic risk for obesity and T2D, offsetting genetic effects; whether this effect is larger for individuals who have high risk for other (unobserved) reasons, i.e., at higher quantiles of HbA1c and BMI; and whether effects differ by gender. We measured T2D risk using Hemoglobin A1c (HbA1c) level, and obesity risk using body-mass index (BMI). We constructed separate genetic risk scores (GRS) for obesity and diabetes respectively based on the most current available information on the single nucleotide polymorphism (SNPs) confirmed as genome-wide significant predictors for BMI (29 SNPs) and diabetes risk (39 SNPs). Linear regression models with years of schooling indicate that the effect of genetic risk on HbA1c is smaller among people with more years of schooling and larger among those with less than a high school (HS) degree compared to HS degree-holders. Quantile regression models show that the GRS × education effect systematically increased along the HbA1c outcome distribution; for example the GRS × years of education interaction coefficient was -0.01 (95% CI = -0.03, 0.00) at the 10th percentile compared to -0.03 (95% CI = -0.07, 0.00) at the 90th percentile. These results suggest that education may be an important socioeconomic source of heterogeneity in responses to genetic vulnerability to T2D.

  1. Effect of magnesium ion supplementation on obesity and diabetes mellitus in Otsuka Long-Evans Tokushima Fatty (OLETF) rats under excessive food intake.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa

    2013-01-01

    Several epidemiologic studies have found that magnesium ion (Mg²⁺) is related to obesity and type 2 diabetes mellitus. However, there have been almost no reports on the effects of a combination of excessive food intake and Mg²⁺ supplementation on metabolic syndrome and various blood tests values for diabetes mellitus. In this study, we investigated changes in body weight and blood test values for diabetes mellitus of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for human type 2 diabetes mellitus via metabolic syndrome, under conditions of combined excessive food intake and Mg²⁺ supplementation. The rats received Mg²⁺ supplementation by drinking magnesium water (Mg²⁺; 200 mg/l). No significant differences were observed in the levels of food or water intake between OLETF rats drinking purified water (PW) or magnesium water (MW). Type 2 diabetes mellitus with metabolic syndrome developed at 30 weeks of age, and the body weights and plasma insulin levels of OLETF rats at 60 weeks of age were lower than those of normal rats. The plasma glucose (PG) levels in 38-week-old OLETF rats drinking MW were significantly lower than in those of rats drinking PW, while the body weights and the levels of triglycerides (TG) and insulin of 38-week-old MW-drinking OLETF rats were significantly higher than those of their PW-drinking counterparts. On the other hand, the decreases in body weight and insulin levels in 60-week-old OLETF rats were suppressed by MW supplementation. The present study demonstrates that Mg²⁺ supplementation delays the development of diabetes mellitus in OLETF rats under conditions of excessive food intake. In addition, obesity and high blood TG levels were observed in OLETF rats receiving Mg²⁺ supplementation in conjunction with excessive food intake.

  2. Controlled downregulation of the cannabinoid CB1 receptor provides a promising approach for the treatment of obesity and obesity-derived type 2 diabetes.

    PubMed

    Lu, Dai; Dopart, Rachel; Kendall, Debra A

    2016-01-01

    Increased activity of the endocannabinoid system has emerged as a pathogenic factor in visceral obesity, which is a risk factor for type 2 diabetes mellitus (T2DM). The endocannabinoid system is composed of at least two Gprotein-coupled receptors (GPCRs), the cannabinoid receptor type 1 (CB1), and the cannabinoid receptor type 2 (CB2). Downregulation of CB1 activity in rodents and humans has proven efficacious to reduce food intake, abdominal adiposity, fasting glucose levels, and cardiometabolic risk factors. Unfortunately, downregulation of CB1 activity by universally active CB1 inverse agonists has been found to elicit psychiatric side effects, which led to the termination of using globally active CB1 inverse agonists to treat diet-induced obesity. Interestingly, preclinical studies have shown that downregulation of CB1 activity by CB1 neutral antagonists or peripherally restricted CB1 inverse agonists provided similar anorectic effects and metabolic benefits without psychiatric side effects seen in globally active CB1 inverse agonists. Furthermore, downregulation of CB1 activity may ease endoplasmic reticulum and mitochondrial stress which are contributors to obesity-induced insulin resistance and type 2 diabetes. This suggests new approaches for cannabinoid-based therapy in the management of obesity and obesity-related metabolic disorders including type 2 diabetes.

  3. Weight for gestational age and metabolically healthy obesity in adults from the Haguenau cohort

    PubMed Central

    Matta, Joane; Carette, Claire; Levy Marchal, Claire; Bertrand, Julien; Pétéra, Mélanie; Zins, Marie; Pujos-Guillot, Estelle; Comte, Blandine; Czernichow, Sébastien

    2016-01-01

    Background An obesity subphenotype, named ‘metabolically healthy obese’ (MHO) has been recently defined to characterise a subgroup of obese individuals with less risk for cardiometabolic abnormalities. To date no data are available on participants born with small weight for gestational age (SGA) and the risk of metabolically unhealthy obesity (MUHO). Objective Assess the risk of MUHO in SGA versus appropriate for gestational age (AGA) adult participants. Methods 129 young obese individuals (body mass index ≥30 kg/m²) from data of an 8-year follow-up Haguenau cohort (France), were identified out of 1308 participants and were divided into 2 groups: SGA (n=72) and AGA (n=57). Metabolic characteristics were analysed and compared using unpaired t-test. The HOMA-IR index was determined for the population and divided into quartiles. Obese participants within the first 3 quartiles were considered as MHO and those in the fourth quartile as MUHO. Relative risks (RRs) and 95% CI for being MUHO in SGA versus AGA participants were computed. Results The SGA-obese group had a higher risk of MUHO versus the AGA-obese group: RR=1.27 (95% CI 1.10 to 1.6) independently of age and sex. Conclusions In case of obesity, SGA might confer a higher risk of MUHO compared with AGA. PMID:27580829

  4. Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review.

    PubMed

    Kagota, Satomi; Maruyama, Kana; McGuire, John J

    2016-01-01

    Proteinase-activated receptor 2 (PAR2) is a cell surface receptor activated by serine proteinases or specific synthetic compounds. Interest in PAR2 as a pharmaceutical target for various diseases is increasing. Here we asked two questions relevant to endothelial dysfunction and diabetes: How is PAR2 function affected in blood vessels? What role does PAR2 have in promoting obesity, diabetes, and/or metabolic syndrome, specifically via the endothelium and adipose tissues? We conducted a systematic review of the published literature in PubMed and Scopus (July 2015; search terms: par2, par-2, f2lr1, adipose, obesity, diabetes, and metabolic syndrome). Seven studies focused on PAR2 and vascular function. The obesity, diabetes, or metabolic syndrome animal models differed amongst studies, but each reported that PAR2-mediated vasodilator actions were preserved in the face of endothelial dysfunction. The remaining studies focused on nonvascular functions and provided evidence supporting the concept that PAR2 activation promoted obesity. Key studies showed that PAR2 activation regulated cellular metabolism, and PAR2 antagonists inhibited adipose gain and metabolic dysfunction in rats. We conclude that PAR2 antagonists for treatment of obesity indeed show early promise as a therapeutic strategy; however, endothelial-specific PAR2 functions, which may offset mechanisms that produce vascular dysfunction in diabetes, warrant additional study. PMID:27006943

  5. Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review

    PubMed Central

    Kagota, Satomi; Maruyama, Kana; McGuire, John J.

    2016-01-01

    Proteinase-activated receptor 2 (PAR2) is a cell surface receptor activated by serine proteinases or specific synthetic compounds. Interest in PAR2 as a pharmaceutical target for various diseases is increasing. Here we asked two questions relevant to endothelial dysfunction and diabetes: How is PAR2 function affected in blood vessels? What role does PAR2 have in promoting obesity, diabetes, and/or metabolic syndrome, specifically via the endothelium and adipose tissues? We conducted a systematic review of the published literature in PubMed and Scopus (July 2015; search terms: par2, par-2, f2lr1, adipose, obesity, diabetes, and metabolic syndrome). Seven studies focused on PAR2 and vascular function. The obesity, diabetes, or metabolic syndrome animal models differed amongst studies, but each reported that PAR2-mediated vasodilator actions were preserved in the face of endothelial dysfunction. The remaining studies focused on nonvascular functions and provided evidence supporting the concept that PAR2 activation promoted obesity. Key studies showed that PAR2 activation regulated cellular metabolism, and PAR2 antagonists inhibited adipose gain and metabolic dysfunction in rats. We conclude that PAR2 antagonists for treatment of obesity indeed show early promise as a therapeutic strategy; however, endothelial-specific PAR2 functions, which may offset mechanisms that produce vascular dysfunction in diabetes, warrant additional study. PMID:27006943

  6. New approaches to gene discovery with animal models of obesity and diabetes.

    PubMed

    Collier, Greg; Walder, Ken; De Silva, Andrea; Tenne-Brown, Janette; Sanigorski, Andrew; Segal, David; Kantham, Lakshmi; Augert, Guy

    2002-06-01

    DNA-based approaches to the discovery of genes contributing to the development of type 2 diabetes have not been very successful despite substantial investments of time and money. The multiple gene-gene and gene-environment interactions that influence the development of type 2 diabetes mean that DNA approaches are not the ideal tool for defining the etiology of this complex disease. Gene expression-based technologies may prove to be a more rewarding strategy to identify diabetes candidate genes. There are a number of RNA-based technologies available to identify genes that are differentially expressed in various tissues in type 2 diabetes. These include differential display polymerase chain reaction (ddPCR), suppression subtractive hybridization (SSH), and cDNA microarrays. The power of new technologies to detect differential gene expression is ideally suited to studies utilizing appropriate animal models of human disease. We have shown that the gene expression approach, in combination with an excellent animal model such as the Israeli sand rat (Psammomys obesus), can provide novel genes and pathways that may be important in the disease process and provide novel therapeutic approaches. This paper will describe a new gene discovery, beacon, a novel gene linked with energy intake. As the functional characterization of novel genes discovered in our laboratory using this approach continues, it is anticipated that we will soon be able to compile a definitive list of genes that are important in the development of obesity and type 2 diabetes.

  7. Alterations in skeletal muscle protein-tyrosine phosphatase activity and expression in insulin-resistant human obesity and diabetes.

    PubMed Central

    Ahmad, F; Azevedo, J L; Cortright, R; Dohm, G L; Goldstein, B J

    1997-01-01

    Obese human subjects have increased protein-tyrosine phosphatase (PTPase) activity in adipose tissue that can dephosphorylate and inactivate the insulin receptor kinase. To extend these findings to skeletal muscle, we measured PTPase activity in the skeletal muscle particulate fraction and cytosol from a series of lean controls, insulin-resistant obese (body mass index > 30) nondiabetic subjects, and obese individuals with non-insulin-dependent diabetes. PTPase activities in subcellular fractions from the nondiabetic obese subjects were increased to 140-170% of the level in lean controls (P < 0.05). In contrast, PTPase activity in both fractions from the obese subjects with non-insulin-dependent diabetes was significantly decreased to 39% of the level in controls (P < 0.05). By immunoblot analysis, leukocyte antigen related (LAR) and protein-tyrosine phosphatase 1B had the greatest increase (threefold) in the particulate fraction from obese, nondiabetic subjects, and immunodepletion of this fraction using an affinity-purified antibody directed at the cytoplasmic domain of leukocyte antigen related normalized the PTPase activity when compared to the activity from control subjects. These findings provide further support for negative regulation of insulin action by specific PTPases in the pathogenesis of insulin resistance in human obesity, while other regulatory mechanisms may be operative in the diabetic state. PMID:9218523

  8. Acupoint catgut embedding therapy with moxibustion reduces the risk of diabetes in obese women

    PubMed Central

    Garcia-Vivas, Jessica M.; Galaviz-Hernandez, Carlos; Becerril-Chavez, Flavia; Lozano-Rodriguez, Francisco; Zamorano-Carrillo, Absalom; Lopez-Camarillo, Cesar; Marchat, Laurence A.

    2014-01-01

    Background: Obesity is a major health problem worldwide for which conventional therapy efficacy is limited. Traditional Chinese medicine, particularly body acupoint stimulation, provides an alternative, effective, and safe therapy for this medical challenge. The present study was designed to compare the effects of distinct methods to stimulate the same set of acupoints, on anthropometric and biochemical parameters in obese women. Materials and Methods: Ninety-nine obese women were randomly assigned to six groups of treatment: Acupuncture with moxibustion, long needle acupuncture with moxibustion, electroacupuncture (EA), EA with moxibustion, embedded catgut with moxibustion (CGM) and sham acupuncture as control. Obesity-related parameters, including body weight, body mass index (BMI), waist and hip circumferences, waist/hip ratio, biochemical parameters (triglycerides, cholesterol, glucose, insulin) and homeostasis model of assessment - insulin resistance (HOMA-IR) index, were determined before and after each treatment. Results: Body weight and BMI were significantly reduced in response to all treatments. Interestingly, acupoint catgut embedding therapy combined with moxibustion was the only treatment that produced a significant reduction in body weight (3.1 ± 0.2 kg, P < 0.001), BMI (1.3 ± 0.1 kg/m2, P < 0.001), insulin (3.5 ± 0.8 mcU/ml, P < 0.1) and HOMA-IR (1.4 ± 0.2 units, P < 0.01) in comparison with sham group. Furthermore, this treatment was able to bring back obese women to a state of insulin sensitivity, indicating that acupoint catgut embedding therapy combined with moxibustion could be useful as a complementary therapy to reduce the risk of diabetes associated to obesity in women. Conclusion: Overall, our results confirmed the effectiveness of acupoints stimulation to assist in the control of body weight in women. They also highlighted the more favorable effects of embedded catgut-moxibustion combination that may be due to the extended and

  9. Ethnic differences in the relationships between diabetes, early age adiposity and mortality among breast cancer survivors: the Breast Cancer Health Disparities Study.

    PubMed

    Connor, Avonne E; Visvanathan, Kala; Baumgartner, Kathy B; Baumgartner, Richard N; Boone, Stephanie D; Hines, Lisa M; Wolff, Roger K; John, Esther M; Slattery, Martha L

    2016-05-01

    The contribution of type 2 diabetes and obesity on mortality in breast cancer (BC) patients has not been well studied among Hispanic women, in whom these exposures are highly prevalent. In a multi-center population-based study, we examined the associations between diabetes, multiple obesity measures, and mortality in 1180 Hispanic and 1298 non-Hispanic white (NHW) women who were diagnosed with incident invasive BC from the San Francisco Bay Area, New Mexico, Utah, Colorado, and Arizona. Adjusted hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards regression models. The median follow-up time from BC diagnosis to death was 10.8 years. In ethnic-stratified results, the association for BC-specific mortality among Hispanics was significantly increased (HR 1.85 95 % CI 1.11, 3.09), but the ethnic interaction was not statistically significant. In contrast, obesity at age 30 increased BC-specific mortality risk in NHW women (HR 2.33 95 % CI 1.36, 3.97) but not Hispanics (p-interaction = 0.045). Although there were no ethnic differences for all-cause mortality, diabetes, obesity at age 30, and post-diagnostic waist-hip ratio were significantly associated with all-cause mortality in all women. This study provides evidence that diabetes and adiposity, both modifiable, are prognostic factors among Hispanic and NHW BC patients.

  10. [Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome].

    PubMed

    Halmos, Tamás; Suba, Ilona

    2016-01-01

    The intestinal microbiota is well-known for a long time, but due to newly recognized functions, clinician's attention has turned to it again in the last decade. About 100 000 billion bacteria are present in the human intestines. The composition of bacteriota living in diverse parts of the intestinal tract is variable according to age, body weight, geological site, and diet as well. Normal bacteriota defend the organism against the penetration of harmful microorganisms, and has many other functions in the gut wall integrity, innate immunity, insulin sensitivity, metabolism, and it is in cross-talk with the brain functions as well. It's a recent recognition, that intestinal microbiota has a direct effect on the brain, and the brain also influences the microbiota. This two-way gut-brain axis consists of microbiota, immune and neuroendocrine system, as well as of the autonomic and central nervous system. Emerging from fermentation of carbohydrates, short-chain fatty acids develop into the intestines, which produce butyrates, acetates and propionates, having favorable effects on different metabolic processes. Composition of the intestinal microbiota is affected by the circadian rhythm, such as in shift workers. Dysruption of circadian rhythm may influence intestinal microbiota. The imbalance between the microbiota and host organism leads to dysbacteriosis. From the membrane of Gram-negative bacteria lipopolysacharides penetrate into the blood stream, via impaired permeability of the intestinal mucosa. These processes induce metabolic endotoxaemia, inflammation, impaired glucose metabolism, insulin resistance, obesity, and contribute to the development of metabolic syndrome, type 2 diabetes, inflammarory bowel diseases, autoimmunity and carcinogenesis. Encouraging therapeutic possibility is to restore the normal microbiota either using pro- or prebiotics, fecal transplantation or bariatric surgery. Human investigations seem to prove that fecal transplant from lean

  11. [Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome].

    PubMed

    Halmos, Tamás; Suba, Ilona

    2016-01-01

    The intestinal microbiota is well-known for a long time, but due to newly recognized functions, clinician's attention has turned to it again in the last decade. About 100 000 billion bacteria are present in the human intestines. The composition of bacteriota living in diverse parts of the intestinal tract is variable according to age, body weight, geological site, and diet as well. Normal bacteriota defend the organism against the penetration of harmful microorganisms, and has many other functions in the gut wall integrity, innate immunity, insulin sensitivity, metabolism, and it is in cross-talk with the brain functions as well. It's a recent recognition, that intestinal microbiota has a direct effect on the brain, and the brain also influences the microbiota. This two-way gut-brain axis consists of microbiota, immune and neuroendocrine system, as well as of the autonomic and central nervous system. Emerging from fermentation of carbohydrates, short-chain fatty acids develop into the intestines, which produce butyrates, acetates and propionates, having favorable effects on different metabolic processes. Composition of the intestinal microbiota is affected by the circadian rhythm, such as in shift workers. Dysruption of circadian rhythm may influence intestinal microbiota. The imbalance between the microbiota and host organism leads to dysbacteriosis. From the membrane of Gram-negative bacteria lipopolysacharides penetrate into the blood stream, via impaired permeability of the intestinal mucosa. These processes induce metabolic endotoxaemia, inflammation, impaired glucose metabolism, insulin resistance, obesity, and contribute to the development of metabolic syndrome, type 2 diabetes, inflammarory bowel diseases, autoimmunity and carcinogenesis. Encouraging therapeutic possibility is to restore the normal microbiota either using pro- or prebiotics, fecal transplantation or bariatric surgery. Human investigations seem to prove that fecal transplant from lean

  12. The natural killer T lymphocyte: a player in the complex regulation of autoimmune diabetes in non-obese diabetic mice

    PubMed Central

    Cardell, S L

    2006-01-01

    Manipulation of the immune response to specifically prevent autoaggression requires an understanding of the complex interactions that occur during the pathogenesis of autoimmunity. Much attention has been paid to conventional T lymphocytes recognizing peptide antigens presented by classical major histocompatibility complex (MHC) class I and II molecules, as key players in the destructive autoreactive process. A pivotal role for different types of regulatory T lymphocytes in modulating the development of disease is also well established. Lately, CD1d-restricted natural killer T (NKT) lymphocytes have been the subject of intense investigation because of their ability to regulate a diversity of immune responses. The non-classical antigen presenting molecule CD1d presents lipids and glycolipids to this highly specialized subset of T lymphocytes found in both humans and mice. From experimental models of autoimmunity, evidence is accumulating that NKT cells can protect from disease. One of the best studied is the murine type 1 diabetes model, the non-obese diabetic (NOD) mouse. While the NKT cell population was first recognized to be deficient in NOD mice, augmenting NKT cell activity has been shown to suppress the development of autoimmune disease in this strain. The mechanism by which CD1d-restricted T cells exert this function is still described incompletely, but investigations in NOD mice are starting to unravel specific effects of NKT cell regulation. This review focuses on the role of CD1d-restricted NKT cells in the control of autoimmune diabetes. PMID:16412042

  13. Biology of Beige Adipocyte and Possible Therapy for Type 2 Diabetes and Obesity

    PubMed Central

    2016-01-01

    All mammals own two main forms of fat. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat. Since adult humans possess significant amounts of active brown fat depots and their mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate itself from white adipocytes. Importantly, adult human brown adipocyte appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases. Because many epigenetic changes can affect beige adipocyte differentiation, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important for therapeutic strategies. In this review we discuss some recent observations arising from the great physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2. PMID:27528872

  14. Biology of Beige Adipocyte and Possible Therapy for Type 2 Diabetes and Obesity.

    PubMed

    Lizcano, Fernando; Vargas, Diana

    2016-01-01

    All mammals own two main forms of fat. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat. Since adult humans possess significant amounts of active brown fat depots and their mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate itself from white adipocytes. Importantly, adult human brown adipocyte appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases. Because many epigenetic changes can affect beige adipocyte differentiation, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important for therapeutic strategies. In this review we discuss some recent observations arising from the great physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2. PMID:27528872

  15. Insights into the role of the microbiome in obesity and type 2 diabetes.

    PubMed

    Hartstra, Annick V; Bouter, Kristien E C; Bäckhed, Fredrik; Nieuwdorp, Max

    2015-01-01

    The worldwide prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise at an alarming pace. Recently the potential role of the gut microbiome in these metabolic disorders has been identified. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome seems to be more efficient in harvesting energy from the diet. Lean male donor fecal microbiota transplantation (FMT) in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. Such differences in gut microbiota composition might function as early diagnostic markers for the development of T2DM in high-risk patients. Products of intestinal microbes such as butyrate may induce beneficial metabolic effects through enhancement of mitochondrial activity, prevention of metabolic endotoxemia, and activation of intestinal gluconeogenesis via different routes of gene expression and hormone regulation. Future research should focus on whether bacterial products (like butyrate) have the same effects as the intestinal bacteria that produce it, in order to ultimately pave the way for more successful interventions for obesity and T2DM. The rapid development of the currently available techniques, including use of fecal transplantations, has already shown promising results, so there is hope for novel therapies based on the microbiota in the future.

  16. Elimination of infused branched-chain amino-acids from plasma of patients with non-obese type 2 diabetes mellitus.

    PubMed

    Marchesini, G; Bianchi, G P; Vilstrup, H; Capelli, M; Zoli, M; Pisi, E

    1991-04-01

    Increased plasma levels of branched-chain amino-acids (BCAA) have been demonstrated in poorly controlled diabetes mellitus, and related to absolute or relative insulin deficiency. To study the pathogenesis of this alteration, the elimination of BCAA from plasma was measured in 8 patients with non-obese type 2 diabetes mellitus and in 8 age-matched control subjects during steady-state BCAA concentrations induced by a primed-continuous infusion. Fasting BCAA levels were increased by 40-50% in patients with diabetes. The plasma clearances of valine, isoleucine, and leucine, calculated as infusion rate divided by steady-state concentration, were reduced by 20% in diabetics, despite 50% hyperinsulinemia (P < 0.01). Basal BCAA levels and BCAA clearance were negatively correlated (r(2) = 0.46 - 0.56). The endogenous basal appearance rates of BCAA, estimated by the basal concentrations multiplied by the plasma clearances, were normal in diabetics, and there was no difference in the apparent volumes of distribution of BCAA. The increased basal concentration of BCAA in poorly controlled type 2 diabetics (693 [SD 114; n = 8] mumol/l vs 479 [88; n = 8] in controls (P < 0.005) is attributable to changes in plasma clearances, without any change in the efflux of BCAA into plasma. This may be due to insulin resistance.

  17. Role of adiponectin and some other factors linking type 2 diabetes mellitus and obesity

    PubMed Central

    Chakraborti, Chandra Kanti

    2015-01-01

    Because of the intimate association of obesity with type 2 diabetes mellitus (T2DM), during the last two decades, extensive research work is being conducted to find out whether the coexistence of the two is a simple association or there is a positive correlating link between the two. In this article, an attempt has been made to collect and analyse the recent developments in this field and to arrive at a conclusion on the subject. The possible role of several important factors (obtained from adipocytes/not of adipocyte origin) in linking the two has been discussed in detail. Some of the agents, specifically adiponectin, are beneficial (i.e., reduce the incidence of both), while others are harmful (i.e., increase their incidence). From the analysis, it appears that obesity and T2DM are intimately linked. PMID:26557957

  18. Sweet Dopamine: Sucrose Preferences Relate Differentially to Striatal D2 Receptor Binding and Age in Obesity.

    PubMed

    Pepino, Marta Y; Eisenstein, Sarah A; Bischoff, Allison N; Klein, Samuel; Moerlein, Stephen M; Perlmutter, Joel S; Black, Kevin J; Hershey, Tamara

    2016-09-01

    Alterations in dopaminergic circuitry play a critical role in food reward and may contribute to susceptibility to obesity. Ingestion of sweets releases dopamine in striatum, and both sweet preferences and striatal D2 receptors (D2R) decline with age and may be altered in obesity. Understanding the relationships between these variables and the impact of obesity on these relationships may reveal insight into the neurobiological basis of sweet preferences. We evaluated sucrose preferences, perception of sweetness intensity, and striatal D2R binding potential (D2R BPND) using positron emission tomography with a D2R-selective radioligand insensitive to endogenous dopamine, (N-[(11)C] methyl)benperidol, in 20 subjects without obesity (BMI 22.5 ± 2.4 kg/m(2); age 28.3 ± 5.4 years) and 24 subjects with obesity (BMI 40.3 ± 5.0 kg/m(2); age 31.2 ± 6.3 years). The groups had similar sucrose preferences, sweetness intensity perception, striatal D2R BPND, and age-related D2R BPND declines. However, both striatal D2R BPND and age correlated with sucrose preferences in subjects without obesity, explaining 52% of their variance in sucrose preference. In contrast, these associations were absent in the obese group. In conclusion, the age-related decline in D2R was not linked to the age-related decline in sweetness preferences, suggesting that other, as-yet-unknown mechanisms play a role and that these mechanisms are disrupted in obesity. PMID:27307220

  19. Preventive Effect of Boiogito on Metabolic Disorders in the TSOD Mouse, a Model of Spontaneous Obese Type II Diabetes Mellitus

    PubMed Central

    Shimada, Tsutomu; Akase, Tomoko; Kosugi, Mitsutaka; Aburada, Masaki

    2011-01-01

    “Boiogito” is a Kampo preparation which has been used since ancient times in patients with obesity of the “asthenic constitution” type, so-called “watery obesity”, and its effect has been recognized clinically. In this study, we investigated the anti-obesity effect of Boiogito in the TSOD (Tsumura Suzuki Obese Diabetes) mouse, a model of spontaneous obese type II diabetes mellitus. Boiogito showed a significant anti-obesity effect in TSOD mice by suppressing body weight gain in a dosage-dependent manner. In addition, Boiogito showed significant ameliorative effects on features of metabolic syndrome such as hyperinsulinemia, fasting hyperglycemia and abnormal lipid metabolism. Regarding lipid accumulation in TSOD mice, Boiogito showed a significant suppressive effect on accumulation of subcutaneous fat, but the effect on the visceral fat accumulation that constitutes the basis of metabolic syndrome was weak, and the suppressive effect on insulin resistance was also weak. Furthermore, Boiogito did not alleviate the abnormal glucose tolerance, the hypertension or the peripheral neuropathy characteristically developed in the TSOD mice. In contrast, in the TSNO (Tsumura Suzuki Non-Obesity) mice used as controls, Boiogito suppressed body weight gain and accumulation of subcutaneous and visceral fat. The above results suggested that Boiogito is effective as an anti-obesity drug against obesity of the “asthenic constitution” type in which subcutaneous fat accumulates, but cannot be expected to exert a preventive effect against various symptoms of metabolic syndrome that are based on visceral fat accumulation. PMID:19208721

  20. Associations of A-FABP with Anthropometric and Metabolic Indices and Inflammatory Cytokines in Obese Patients with Newly Diagnosed Type 2 Diabetes

    PubMed Central

    Niu, Guifen; Li, Jian; Wang, Huaiguo; Ren, Yuan

    2016-01-01

    The study aimed to evaluate the relationship between anthropometric and metabolic indices, inflammatory cytokines, and adipocyte fatty acid-binding protein (A-FABP) in obese patients with newly diagnosed type 2 diabetes. The study included 48 nonobese subjects with newly diagnosed type 2 diabetes, 42 obese subjects with newly diagnosed type 2 diabetes, 30 simple obese subjects, and 30 matched normal subjects. Serum A-FABP was assessed by enzyme-linked immunosorbent assay. Pearson's correlations and multiple linear regression stepwise analysis were used to analyze correlations of A-FABP with anthropometric and metabolic indices and inflammatory cytokines. Obese subjects with newly diagnosed type 2 diabetes had elevated A-FABP compared to normal control, nondiabetic obese patients, and nonobese diabetic patients. A-FABP was significantly correlated with glycated hemoglobin A1C (HbA1C), BMI, triglyceride, Homeostasis Model Assessment Index (HOMA-IR), waist hip rate, C-reactive protein, IL-6, and HDL-C in obese subjects with type 2 diabetes. In multiple linear regression stepwise analysis, BMI, HbA1C, and HOMA-IR were significantly independent determinants for A-FABP. BMI, HbA1C, and HOMA-IR are independently associated with A-FABP in obese subjects with newly diagnosed type 2 diabetes. A-FABP may be related to insulin resistance and inflammation in type 2 diabetes and concomitant obesity.

  1. What Is the Best NGS Enrichment Method for the Molecular Diagnosis of Monogenic Diabetes and Obesity?

    PubMed

    Philippe, Julien; Derhourhi, Mehdi; Durand, Emmanuelle; Vaillant, Emmanuel; Dechaume, Aurélie; Rabearivelo, Iandry; Dhennin, Véronique; Vaxillaire, Martine; De Graeve, Franck; Sand, Olivier; Froguel, Philippe; Bonnefond, Amélie

    2015-01-01

    Molecular diagnosis of monogenic diabetes and obesity is of paramount importance for both the patient and society, as it can result in personalized medicine associated with a better life and it eventually saves health care spending. Genetic clinical laboratories are currently switching from Sanger sequencing to next-generation sequencing (NGS) approaches but choosing the optimal protocols is not easy. Here, we compared the sequencing coverage of 43 genes involved in monogenic forms of diabetes and obesity, and variant detection rates, resulting from four enrichment methods based on the sonication of DNA (Agilent SureSelect, RainDance technologies), or using enzymes for DNA fragmentation (Illumina Nextera, Agilent HaloPlex). We analyzed coding exons and untranslated regions of the 43 genes involved in monogenic diabetes and obesity. We found that none of the methods achieves yet full sequencing of the gene targets. Nonetheless, the RainDance, SureSelect and HaloPlex enrichment methods led to the best sequencing coverage of the targets; while the Nextera method resulted in the poorest sequencing coverage. Although the sequencing coverage was high, we unexpectedly found that the HaloPlex method missed 20% of variants detected by the three other methods and Nextera missed 10%. The question of which NGS technique for genetic diagnosis yields the highest diagnosis rate is frequently discussed in the literature and the response is still unclear. Here, we showed that the RainDance enrichment method as well as SureSelect, which are both based on the sonication of DNA, resulted in a good sequencing quality and variant detection, while the use of enzymes to fragment DNA (HaloPlex or Nextera) might not be the best strategy to get an accurate sequencing. PMID:26599467

  2. Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy.

    PubMed

    Isidro, M Luisa; Penín, Manuel A; Nemiña, Rosa; Cordido, Fernando

    2007-08-01

    Context It has been reported that metformin might modify thyroid hormone economy. In two retrospective studies, initiation of treatment with metformin caused suppression of TSH to subnormal levels. Objective To prospectively evaluate if administration of metformin to obese, diabetic patients with primary hypothyroidism on stable thyroxine replacement doses modifies TSH levels. Patients and methods Eight obese, diabetic postmenopausal women with primary hypothyroidism participated in the study. They received 1,700 mg of metformin daily for 3 months. Weight, TSH, free T4, and free T3 levels were measured at baseline, 3 months after metformin initiation and 3 months after its withdrawal. Results After 3 months of on metformin, mean TSH was significantly lower than basal TSH (3.11 +/- 0.50 microUI/ml vs. 1.18 +/- 0.36 microUI/ml; P = 0.01). Mean TSH 3 months after metformin withdrawal was 2.21 +/- 0.37 microUI/ml, significantly higher than TSH after metformin (P = 0.05), but not different from basal TSH. Mean fT4 level increased during metformin administration (basal fT4: 1.23 +/- 0.06 ng/dl, fT4 after metformin: 1.32 +/- 0.04 ng/dl; P = ns), and decreased after its withdrawal (fT4 3 months after metformin withdrawal: 1.15 +/- 0.05 ng/dl; vs. 3 months after metformin, P = 0.04; vs. basal; P = ns). Conclusions In obese, diabetic patients with primary hypothyroidism on thyroxine replacement treatment, short-term metformin administration is associated with a significant fall in TSH. PMID:17992605

  3. Involvement of splenic iron accumulation in the development of nonalcoholic steatohepatitis in Tsumura Suzuki Obese Diabetes mice

    PubMed Central

    Murotomi, Kazutoshi; Arai, Shigeyuki; Uchida, Satoko; Endo, Shin; Mitsuzumi, Hitoshi; Tabei, Yosuke; Yoshida, Yasukazu; Nakajima, Yoshihiro

    2016-01-01

    Nonalcoholic steatohepatitis (NASH) is a common hepatic manifestation of metabolic syndrome and can lead to hepatic cirrhosis and cancer. It is considered that NASH is caused by multiple parallel events, including abnormal lipid metabolism, gut-derived-endotoxin-induced inflammation, and adipocytokines derived from adipose tissue, suggesting that other tissues are involved in NASH development. Previous studies demonstrated that spleen enlargement is observed during the course of NASH pathogenesis. However, the involvement of splenic status in the progression of NASH remains unclear. In this study, we examined hepatic and splenic histopathological findings in the early stage of NASH using the Tsumura Suzuki Obese Diabetes (TSOD) mouse model established for assessing NASH. We found that 12-week-old TSOD mice clearly exhibited the histopathological features of NASH in the early stage. At this age, the spleen of TSOD mice showed markedly higher iron level than that of control Tsumura Suzuki Non Obesity (TSNO) mice. The level of accumulated iron was significantly decreased by feeding a diet with glucosyl hesperidin, a bioactive flavonoid, accompanied with alleviation of hepatic lesions. Furthermore, we found that splenic iron level was positively correlated with the severity of NASH manifestations, suggesting that abnormalities in the spleen are involved in the development of NASH. PMID:26932748

  4. Type 2 diabetes mellitus and impaired glucose regulation in overweight and obese children and adolescents living in Serbia.

    PubMed

    Vukovic, R; Mitrovic, K; Milenkovic, T; Todorovic, S; Zdravkovic, D

    2012-11-01

    An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by numerous studies in the United States during the past two decades. Available data from Europe are scarce, but also suggest the rising prevalence of this disease in overweight children. The aim of this study was to determine the prevalence of previously undiagnosed T2DM, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a clinic cohort of otherwise healthy overweight and obese Caucasian children and adolescents living in Serbia. The study group consisted of 301 subjects (176 girls, 125 boys) aged 5.2-18.9 years, with body mass index >90th percentile. Oral glucose tolerance test was performed in all subjects. Previously undiagnosed T2DM was discovered in 0.3% (n=1) and impaired glucose regulation in 15.9% (n=48) of the subjects. Isolated IFG was detected in 4.3% (n=13), isolated IGT in 8.3% (n=25) and combined IFG and IGT in 3.3% (n=10) of the subjects. Disturbances of glucose metabolism were present in a substantial number of the subjects, which emphasizes the need for prevention and treatment of childhood obesity.

  5. Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography

    PubMed Central

    Kerckhofs, G.; Durand, M.; Vangoitsenhoven, R.; Marin, C.; Van der Schueren, B.; Carmeliet, G.; Luyten, F. P.; Geris, L.; Vandamme, K.

    2016-01-01

    High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging. PMID:27759061

  6. Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models.

    PubMed

    Rajpal, Deepak K; Klein, Jean-Louis; Mayhew, David; Boucheron, Joyce; Spivak, Aaron T; Kumar, Vinod; Ingraham, Karen; Paulik, Mark; Chen, Lihong; Van Horn, Stephanie; Thomas, Elizabeth; Sathe, Ganesh; Livi, George P; Holmes, David J; Brown, James R

    2015-01-01

    The gastrointestinal tract microbiome has been suggested as a potential therapeutic target for metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). However, the relationship between changes in microbial communities and metabolic disease-phenotypes are still poorly understood. In this study, we used antibiotics with markedly different antibacterial spectra to modulate the gut microbiome in a diet-induced obesity mouse model and then measured relevant biochemical, hormonal and phenotypic biomarkers of obesity and T2DM. Mice fed a high-fat diet were treated with either ceftazidime (a primarily anti-Gram negative bacteria antibiotic) or vancomycin (mainly anti-Gram positive bacteria activity) in an escalating three-dose regimen. We also dosed animals with a well-known prebiotic weight-loss supplement, 10% oligofructose saccharide (10% OFS). Vancomycin treated mice showed little weight change and no improvement in glycemic control while ceftazidime and 10% OFS treatments induced significant weight loss. However, only ceftazidime showed significant, dose dependent improvement in key metabolic variables including glucose, insulin, protein tyrosine tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Subsequently, we confirmed the positive hyperglycemic control effects of ceftazidime in the Zucker diabetic fatty (ZDF) rat model. Metagenomic DNA sequencing of bacterial 16S rRNA gene regions V1-V3 showed that the microbiomes of ceftazidime dosed mice and rats were enriched for the phylum Firmicutes while 10% OFS treated mice had a greater abundance of Bacteroidetes. We show that specific changes in microbial community composition are associated with obesity and glycemic control phenotypes. More broadly, our study suggests that in vivo modulation of the microbiome warrants further investigation as a potential therapeutic strategy for metabolic diseases. PMID:26709835

  7. A nonsense polymorphism (R392X) in TLR5 protects from obesity but predisposes to diabetes.

    PubMed

    Al-Daghri, Nasser M; Clerici, Mario; Al-Attas, Omar; Forni, Diego; Alokail, Majed S; Alkharfy, Khalid M; Sabico, Shaun; Mohammed, Abdul Khader; Cagliani, Rachele; Sironi, Manuela

    2013-04-01

    The TLR5 gene encodes an innate immunity receptor. Mice lacking Tlr5 (T5KO) develop insulin resistance and increased adiposity. Owing to the segregation of a dominant nonsense polymorphism (R392X, rs5744168), a portion of humans lack TLR5 function. We investigated whether the nonsense polymorphism influences obesity and susceptibility to type 2 diabetes (T2D). R392X was genotyped in two cohorts from Saudi Arabia, a region where obesity and type 2 diabetes (T2D) are highly prevalent. The nonsense allele was found to protect from obesity (p(combined) = 0.0062; odds ratio, 0.51) and to associate with lower body mass index (BMI) (p(combined) = 0.0061); this allele also correlated with a reduced production of proinflammatory cytokines. A significant interaction was noted between rs5744168 and sex in affecting BMI (p(interaction) = 0.006), and stratification by gender revealed that the association is driven by females (p(combined) = 0.0016 and 0.0006 for obesity and BMI, respectively). The nonsense polymorphism also associated with BMI in nonobese women. After correction for BMI, the 392X allele was found to represent a risk factor for T2D with a sex-specific effect (p(interaction) = 0.023) mediated by females (p = 0.021; odds ratio, 2.60). Fasting plasma glucose levels in nondiabetic individuals were also higher in women carrying the nonsense allele (p = 0.012). Thus, in contrast to T5KO mice, loss of human TLR5 function protects from weight gain, but in analogy to the animal model, the nonsense allele predisposes to T2D. These effects are apparently sex-specific. Data in this study reinforce the hypothesis that metabolic diseases, including T2D, are associated with immune dysregulation.

  8. Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models.

    PubMed

    Rajpal, Deepak K; Klein, Jean-Louis; Mayhew, David; Boucheron, Joyce; Spivak, Aaron T; Kumar, Vinod; Ingraham, Karen; Paulik, Mark; Chen, Lihong; Van Horn, Stephanie; Thomas, Elizabeth; Sathe, Ganesh; Livi, George P; Holmes, David J; Brown, James R

    2015-01-01

    The gastrointestinal tract microbiome has been suggested as a potential therapeutic target for metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). However, the relationship between changes in microbial communities and metabolic disease-phenotypes are still poorly understood. In this study, we used antibiotics with markedly different antibacterial spectra to modulate the gut microbiome in a diet-induced obesity mouse model and then measured relevant biochemical, hormonal and phenotypic biomarkers of obesity and T2DM. Mice fed a high-fat diet were treated with either ceftazidime (a primarily anti-Gram negative bacteria antibiotic) or vancomycin (mainly anti-Gram positive bacteria activity) in an escalating three-dose regimen. We also dosed animals with a well-known prebiotic weight-loss supplement, 10% oligofructose saccharide (10% OFS). Vancomycin treated mice showed little weight change and no improvement in glycemic control while ceftazidime and 10% OFS treatments induced significant weight loss. However, only ceftazidime showed significant, dose dependent improvement in key metabolic variables including glucose, insulin, protein tyrosine tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Subsequently, we confirmed the positive hyperglycemic control effects of ceftazidime in the Zucker diabetic fatty (ZDF) rat model. Metagenomic DNA sequencing of bacterial 16S rRNA gene regions V1-V3 showed that the microbiomes of ceftazidime dosed mice and rats were enriched for the phylum Firmicutes while 10% OFS treated mice had a greater abundance of Bacteroidetes. We show that specific changes in microbial community composition are associated with obesity and glycemic control phenotypes. More broadly, our study suggests that in vivo modulation of the microbiome warrants further investigation as a potential therapeutic strategy for metabolic diseases.

  9. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P.

    2000-06-27

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  10. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P.

    1998-01-01

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  11. Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast™ High-Throughput Data

    PubMed Central

    Auerbach, Scott; Filer, Dayne; Reif, David; Walker, Vickie; Holloway, Alison C.; Schlezinger, Jennifer; Srinivasan, Supriya; Svoboda, Daniel; Judson, Richard; Bucher, John R.; Thayer, Kristina A.

    2016-01-01

    Background: Diabetes and obesity are major threats to public health in the United States and abroad. Understanding the role that chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is challenging. This review is intended to help researchers generate hypotheses about chemicals that may contribute to diabetes and to obesity-related health outcomes by summarizing relevant findings from the U.S. Environmental Protection Agency (EPA) ToxCast™ high-throughput screening (HTS) program. Objectives: Our aim was to develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high-throughput screening data. Methods: We identified ToxCast™ assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and β cell function, adipocyte differentiation, and feeding behavior) and presented chemical screening data against those assay targets to identify chemicals of potential interest. Discussion: The results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated by research papers and reviews published in the peer-reviewed literature. Testing hypotheses based on ToxCast™ data will also help assess the predictive utility of this HTS platform. Conclusions: More research is required to put these screening-level analyses into context, but the information presented in this review should facilitate the development of new hypotheses. Citation: Auerbach S, Filer D, Reif D, Walker V, Holloway AC, Schlezinger J, Srinivasan S, Svoboda D, Judson R, Bucher JR, Thayer KA. 2016. Prioritizing environmental chemicals for obesity and diabetes outcomes research

  12. A small-molecule inhibitor of SHIP1 reverses age- and diet-associated obesity and metabolic syndrome

    PubMed Central

    Srivastava, Neetu; Iyer, Sonia; Sudan, Raki; Youngs, Christie; Engelman, Robert W.; Howard, Kyle T.; Russo, Christopher M.; Chisholm, John D.; Kerr, William G.

    2016-01-01

    Low-grade chronic inflammation is a key etiological phenomenon responsible for the initiation and perpetuation of obesity and diabetes. Novel therapeutic approaches that can specifically target inflammatory pathways are needed to avert this looming epidemic of metabolic disorders. Genetic and chemical inhibition of SH2-containing inositol 5′ phosphatase 1 (SHIP1) has been associated with systemic expansion of immunoregulatory cells that promote a lean-body state; however, SHIP1 function in immunometabolism has never been assessed. This led us to investigate the role of SHIP1 in metabolic disorders during excess caloric intake in mice. Using a small-molecule inhibitor of SHIP1 (SHIPi), here we show that SHIPi treatment in mice significantly reduces body weight and fat content, improves control of blood glucose and insulin sensitivity, and increases energy expenditure, despite continued consumption of a high-fat diet. Additionally, SHIPi reduces age-associated fat in mice. We found that SHIPi treatment reverses diet-associated obesity by attenuating inflammation in the visceral adipose tissue (VAT). SHIPi treatment increases IL-4–producing eosinophils in VAT and consequently increases both alternatively activated macrophages and myeloid-derived suppressor cells. In addition, SHIPi decreases the number of IFN-γ–producing T cells and NK cells in VAT. Thus, SHIPi represents an approach that permits control of obesity and diet-induced metabolic syndrome without apparent toxicity. PMID:27536730

  13. Does obesity influence labour market outcomes among working-age adults? Evidence from Canadian longitudinal data.

    PubMed

    Larose, Samantha L; Kpelitse, Koffi A; Campbell, M Karen; Zaric, Gregory S; Sarma, Sisira

    2016-03-01

    Although a negative association between obesity and labour market outcomes is commonly reported in many studies, the causal nature of this relationship remains unclear. Using nationally representative longitudinal data from the last six confidential master files (2000/2001-2010/2011) of the National Population Health Survey, we examine the association between obesity and employment participation and earnings among working-age adults in Canada. After controlling for demographic and socioeconomic characteristics, lifestyle factors and time-invariant individual heterogeneity, our results show that obesity is not significantly associated with employment participation but is associated with reduced hourly wage rate and annual income among women by about 4% and 4.5%, respectively. The corresponding results for men show that obesity is associated with about 2% reduction in wage rate and income, but significant at 10% level. However, after controlling for the potential reverse causality bias using the lagged measure of obesity, the effect of obesity on wage rate and income became positive or statistically non-significant. Our findings suggest that obesity is not causally associated with negative labour market outcomes among working-age men in Canada. For working-age women, we find limited evidence of negative labour market outcomes. PMID:26650919

  14. Does obesity influence labour market outcomes among working-age adults? Evidence from Canadian longitudinal data.

    PubMed

    Larose, Samantha L; Kpelitse, Koffi A; Campbell, M Karen; Zaric, Gregory S; Sarma, Sisira

    2016-03-01

    Although a negative association between obesity and labour market outcomes is commonly reported in many studies, the causal nature of this relationship remains unclear. Using nationally representative longitudinal data from the last six confidential master files (2000/2001-2010/2011) of the National Population Health Survey, we examine the association between obesity and employment participation and earnings among working-age adults in Canada. After controlling for demographic and socioeconomic characteristics, lifestyle factors and time-invariant individual heterogeneity, our results show that obesity is not significantly associated with employment participation but is associated with reduced hourly wage rate and annual income among women by about 4% and 4.5%, respectively. The corresponding results for men show that obesity is associated with about 2% reduction in wage rate and income, but significant at 10% level. However, after controlling for the potential reverse causality bias using the lagged measure of obesity, the effect of obesity on wage rate and income became positive or statistically non-significant. Our findings suggest that obesity is not causally associated with negative labour market outcomes among working-age men in Canada. For working-age women, we find limited evidence of negative labour market outcomes.

  15. Microbial transmission from mothers with obesity or diabetes to infants: an innovative opportunity to interrupt a vicious cycle.

    PubMed

    Soderborg, Taylor K; Borengasser, Sarah J; Barbour, Linda A; Friedman, Jacob E

    2016-05-01

    Maternal obesity and diabetes dramatically increase the long-term risk for obesity in the next generation, and pregnancy and lactation may be critical periods at which to aim primary prevention to break the obesity cycle. It is becoming increasingly clear that the gut microbiome in newborns and infants plays a significant role in gut health and therefore child development. Alteration of the early infant gut microbiome has been correlated with the development of childhood obesity and autoimmune conditions, including asthma, allergies and, more recently, type 1 diabetes. This is likely to be due to complex interactions between mode of delivery, antibiotic use, maternal diet, components of breastfeeding and a network of regulatory events involving both the innate and adaptive immune systems within the infant host. Each of these factors are critical for informing microbiome development and can affect immune signalling, toxin release and metabolic signals, including short-chain fatty acids and bile acids, that regulate appetite, metabolism and inflammation. In several randomised controlled trials, probiotics have been administered with the aim of targeting the microbiome during pregnancy to improve maternal and infant health but the findings have often been confounded by mode of delivery, antibiotic use, ethnicity, infant sex, maternal health and length of exposure. Understanding how nutritional exposure, including breast milk, affects the assembly and development of both maternal and infant microbial communities may help to identify targeted interventions during pregnancy and in infants born to mothers with obesity or diabetes to slow the transmission of obesity risk to the next generation. The aim of this review is to discuss influences on infant microbiota colonisation and the mechanism(s) underlying how alterations due to maternal obesity and diabetes may lead to increased risk of childhood obesity. PMID:26843076

  16. Obesity and medicare expenditure: accounting for age-related height loss.

    PubMed

    Onwudiwe, Nneka C; Stuart, Bruce; Zuckerman, Ilene H; Sorkin, John D

    2011-01-01

    To determine the relationship between BMI and Medicare expenditure for adults 65-years and older and determine whether this relationship changes after accounting for misclassification due to age-related height loss. Using a cross sectional study design, the relationship between BMI and fee-for-service Medicare expenditure was examined among beneficiaries who completed the Medicare Current Beneficiary Survey (MCBS) in 2002, were not enrolled in Medicare Health Maintenance Organization, had a self-reported height and weight, and were 65 and older (n = 7,706). Subjects were classified as underweight, normal weight, overweight, obese (obese I), and severely obese (obese II/III). To adjust BMI for the artifactual increase associated with age-related height loss, the reported height was transformed by adding the sex-specific age-associated height loss to the reported height in MCBS. The main outcome variable was total Medicare expenditure. There was a significant U-shaped pattern between unadjusted BMI and Medicare expenditure: underweight $4,581 (P < 0.0003), normal weight $3,744 (P < 0.0000), overweight $3,115 (reference), obese I $3,686 (P < 0.0039), and obese II/III $4,386 (P < 0.0000). This pattern persisted after accounting for height loss: underweight $4,640 (P < 0.0000), normal weight $3,451 (P < 0.0507), overweight $3,165 (reference), obese I $3,915 (P < 0.0010), and obese II/III $4,385 (P < 0.0004) compared to overweight. In older adults, minimal cost is not found at "normal" BMI, but rather in overweight subjects with higher spending in the obese and underweight categories. Adjusting for loss-of-height with aging had little affect on cost estimates.

  17. Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity

    PubMed Central

    Okada-Iwabu, Miki; Iwabu, Masato

    2015-01-01

    Obesity associated with unhealthy diet and lack of exercise is shown to contribute to the onset and/or aggravation of the metabolic syndrome and diabetes, thus placing affected individuals at increased risk of cardiovascular disease and cancer. Plasma adiponectin levels are decreased in obesity, which causes insulin resistance and diabetes. Therefore, we identified adiponectin receptors (AdipoRs) as the therapeutic target. It was suggested that, similarly to caloric restriction and exercise, activation of the AdipoRs may have the potential not only to improve lifestyle-related diseases but to contribute to prolonged the shortened lifespan on a high caloric unhealthy diet. To this end, we have identified "AdipoRon" as an adiponectin receptor agonist. Indeed, AdipoRon ameliorated diabetes associated with obesity as well as to increase exercise endurance, thus prolonging shortened lifespan of obese mice fed on a high fat diet. Additionally, we have recently determined the crystal structures of the human AdipoRs. The seven-transmembrane helices of AdipoRs are structurally distinct from those of G-protein coupled receptors. It is expected that these findings will contribute not only to the elucidation of the AdipoR-related signal transduction but to the development and optimization of AdipoR-targeted therapeutics for obesity-related diseases such as diabetes. PMID:26566493

  18. Is There a Reversal in the Effect of Obesity on Mortality in Old Age?

    PubMed Central

    Cohen-Mansfield, Jiska; Perach, Rotem

    2011-01-01

    Studies of obesity and its relationship with mortality risk in older persons have yielded conflicting results. We aimed to examine the age-related associations between obesity and mortality in older persons. Data were drawn from the Cross-Sectional and Longitudinal Aging Study (CALAS), a national survey of a random sample of older Jewish persons in Israel conducted during 1989–1992. Analyses included 1369 self-respondent participants aged 75–94 from the Cross-Sectional and Longitudinal Aging Study (CALAS). Mortality data at 20-year followup were recorded from the Israeli National Population Registry. Obesity was significantly predictive of higher mortality for persons aged 75–84, but from age 85 onwards, obesity had a protective effect on mortality albeit at a nonsignificant level. Being underweight was consistently predictive of mortality. Findings suggest that the common emphasis on avoiding obesity may not apply to those advancing towards old-old age, at least as far as mortality is concerned. PMID:21966593

  19. The association between ownership of common household devices and obesity and diabetes in high, middle and low income countries

    PubMed Central

    Lear, Scott A.; Teo, Koon; Gasevic, Danijela; Zhang, Xiaohe; Poirier, Paul P.; Rangarajan, Sumathy; Seron, Pamela; Kelishadi, Roya; Tamil, Azmi Mohd; Kruger, Annamarie; Iqbal, Romaina; Swidan, Hani; Gómez-Arbeláez, Diego; Yusuf, Rita; Chifamba, Jephat; Kutty, V. Raman; Karsidag, Kubilay; Kumar, Rajesh; Li, Wei; Szuba, Andrzej; Avezum, Alvaro; Diaz, Rafael; Anand, Sonia S.; Rosengren, Annika; Yusuf, Salim

    2014-01-01

    Background: Household devices (e.g., television, car, computer) are common in high income countries, and their use has been linked to obesity and type 2 diabetes mellitus. We hypothesized that device ownership is associated with obesity and diabetes and that these effects are explained through reduced physical activity, increased sitting time and increased energy intake. Methods: We performed a cross-sectional analysis using data from the Prospective Urban Rural Epidemiology study involving 153 996 adults from high, upper-middle, lower-middle and low income countries. We used multilevel regression models to account for clustering at the community and country levels. Results: Ownership of a household device increased from low to high income countries (4% to 83% for all 3 devices) and was associated with decreased physical activity and increased sitting, dietary energy intake, body mass index and waist circumference. There was an increased odds of obesity and diabetes with the ownership of any 1 household device compared to no device ownership (obesity: odds ratio [OR] 1.43, 95% confidence interval [CI] 1.32–1.55; diabetes: OR 1.38, 95% CI 1.28–1.50). Ownership of a second device increased the odds further but ownership of a third device did not. Subsequen