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Sample records for age obesity diabetes

  1. Dynapenic Obesity and Prevalence of Type 2 Diabetes in Middle-Aged Japanese Men

    PubMed Central

    Kawakami, Ryoko; Sawada, Susumu S.; Lee, I-Min; Matsushita, Munehiro; Gando, Yuko; Okamoto, Takashi; Tsukamoto, Koji; Higuchi, Mitsuru; Miyachi, Motohiko; Blair, Steven N.

    2015-01-01

    Background The independent and combined associations of muscle strength and obesity on the prevalence of type 2 diabetes in Japanese men remain unclear. Methods Hand grip strength was cross-sectionally evaluated between 2011 and 2013 to assess muscle strength in 5039 male workers aged 40 to 64 years. Weight and height were measured, and overweight/obesity was defined as a body mass index ≥25 kg/m2. The prevalence of type 2 diabetes, defined as fasting plasma glucose ≥126 mg/dL and/or hemoglobin A1c ≥6.5% and/or self-reported physician-diagnosed diabetes, was evaluated. Odds ratios (OR) and 95% confidence intervals (95% CI) for the prevalence of type 2 diabetes were obtained using a logistic regression model. Results In total, 611 participants had type 2 diabetes, and 1763 participants were overweight/obese. After adjustment for covariates, we found an inverse association between muscle strength and the prevalence of type 2 diabetes (P for trend <0.01). In addition, when the analyses were stratified by obesity status, the multivariable-adjusted OR per 2-standard-deviation increase in muscle strength was 0.64 (95% CI, 0.49–0.83) in the overweight/obese group, compared to a weaker relationship in the normal-weight group (OR 0.79 per 2-standard-deviation increase; 95% CI, 0.60–1.06). Conclusions Dynapenia, an age-related decrease in muscle strength, is associated with increased prevalence of type 2 diabetes, and this relationship is stronger in overweight/obese middle-aged Japanese men than in normal-weight men. PMID:26256772

  2. Ocular Inflammation in Uveal Tract in Aged Obese Type 2 Diabetic Rats (Spontaneously Diabetic Torii Fatty Rats)

    PubMed Central

    Kemmochi, Yusuke; Miyajima, Katsuhiro; Ohta, Takeshi; Yasui, Yuzo; Toyoda, Kaoru; Kakimoto, Kochi; Shoda, Toshiyuki

    2014-01-01

    We report uveitis observed in an obese type 2 diabetes rat model, Spontaneously Diabetic Torii Leprfa (SDT fatty) rats aged over 50 weeks. The eyes of SDT fatty rats (16 animals: 7 males and 9 females with 50 or 60 weeks of age) were examined histopathologically. Infiltration of inflammatory cells in the uveal tract was observed in 13 of 16 animals. One female showed severe inflammation affecting the entire uveal tract including the iris, ciliary body, and choroid with a variety of inflammatory cells (neutrophils, lymphocytes, and macrophages). Those changes clinically mimic the findings of diabetic iridocyclitis in diabetic patients. Uveitis associated with diabetes can occur in diabetic patients but the pathogenesis still remains unknown. Since increased extramedullary hematopoiesis in the spleen and abscess in the genital and lower urinary tracts were observed in some SDT fatty rats, increased susceptibility to infection, prolongation of inflammatory states, and disorders of the immune system were considered to be possible factors of the uveitis in aged SDT fatty rats. There have been few reports on how diabetes has influence on the development of uveitis associated with bacterial infection. The SDT fatty rat can be an animal model to investigate diabetes-associated uveitis. PMID:25295283

  3. Respiratory Sinus Arrhythmia and Diseases of Aging: Obesity, Diabetes Mellitus, and Hypertension.

    PubMed Central

    Masi, Christopher M.; Hawkley, Louise C.; Rickett, Edith M.; Cacioppo, John T.

    2007-01-01

    Associations between respiratory sinus arrhythmia (RSA) and several chronic diseases, including obesity, diabetes mellitus, and hypertension, have been documented in recent years. Although most evidence suggests reduced RSA is the result of chronic disease rather than the cause, some studies have documented reduced RSA among at-risk individuals prior to disease onset. These results raise the possibility that decreased vagal tone may play a role in the pathogenesis of certain chronic diseases. Presented here is a brief overview of studies which examine the relationship between vagal tone, as measured by RSA and baroreflex gain, and diseases of aging, including obesity, diabetes mellitus, and hypertension. Mechanisms by which vagal tone may be related to disease processes are discussed. In addition, we present results from a population-based study of RSA and hypertension in older adults. Consistent with previous studies, we found an inverse relationship between RSA and age, cigarette use, and diabetes. In logistic regression models which control for age, cigarette use, and diabetes, we found RSA was a significant negative predictor of hypertension. We conclude that the relationship between RSA and hypertension is somewhat independent of the age-related decline in parasympathetic activity. PMID:17034928

  4. 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

  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. PMID:26337083

  6. 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

  7. 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

  8. 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

  9. 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

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

    PubMed

    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

  11. Angiogenesis in Diabetes and Obesity

    PubMed Central

    Cheng, Rui; Ma, Jian-xing

    2015-01-01

    The prevalence of diabetes mellitus and obesity continues to increase globally. Diabetic vascular complications are the main chronic diabetic complications and associated with mortality and disability. Angiogenesis is a key pathological characteristic of diabetic microvascular complications. However, there are two tissue-specific paradoxical changes in the angiogenesis in diabetic microvascular complications: an excessive uncontrolled formation of premature blood vessels in some tissues, such as the retina, and a deficiency in the formation of small blood vessels in peripheral tissues, such as the skin. This review will discuss the paradoxical phenomena of angiogenesis and its underlying mechanism in obesity, diabetes and diabetic complications. PMID:25663658

  12. Obesity, Diabetes and Survival in Maintenance Hemodialysis Patients

    PubMed Central

    Deger, Serpil M.; Ellis, Charles D.; Bian, Ahuia; Shintani, Ayumi; Ikizler, T. Alp; Hung, Adriana M.

    2016-01-01

    Increased body mass index (BMI) confers a survival advantage in maintenance hemodialysis (MHD) patients. Diabetic (DM) patients undergoing MHD have worse survival. There are limited studies examining the effect of obesity on the risk of death among MHD patients with diabetes. Ninety-eight MHD patients were studied for median follow-up time of 78 months. Patients were classified according to the presence of obesity (BMI ≥ 30 kg/m2) or DM. Primary outcome was all-cause mortality. Cox regression was used to evaluate the effect of obesity on time to death. Effect modification and mediation analysis were also performed. Mean age was 49 ± 13 years, 66% were male, 48% were obese and 34% were diabetic. Mortality rates (per 100 person years) were: 3.4 for non-diabetic obese, 8.6 for non-diabetic non-obese, 14.3 for diabetic non-obese and 18.1 for diabetic obese patients. Log-rank comparing diabetic obese versus non diabetic obese was significant (p=0.007). Diabetes was associated with an increased risk of mortality after adjustment for potential mediators. Effect modification of obesity in the mortality risk was different between patients with and without diabetes. With adjustment for adipokines, a greater effect modification by diabetes was observed whereas adjustment for inflammatory marker did not influence the effect modification. Diabetic obese MHD patients have increased mortality risk compared to non-diabetic obese. Obesity does not offer survival benefits in Diabetic obese MHD patients and potentially may have detrimental effects. Larger studies evaluating the effect of adipokines and obesity in outcomes in the diabetic MHD population need to be undertaken. PMID:24467439

  13. 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

  14. 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

  15. 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

  16. Psoriasis Tied to Obesity, Type 2 Diabetes

    MedlinePlus

    ... gov/news/fullstory_158526.html Psoriasis Tied to Obesity, Type 2 Diabetes A genetic link is one ... prove that psoriasis causes type 2 diabetes or obesity or vice versa, Lonnberg added. However, the study ...

  17. Psoriasis Tied to Obesity, Type 2 Diabetes

    MedlinePlus

    ... medlineplus/news/fullstory_158526.html Psoriasis Tied to Obesity, Type 2 Diabetes A genetic link is one ... prove that psoriasis causes type 2 diabetes or obesity or vice versa, Lonnberg added. However, the study ...

  18. [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

  19. 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

  20. Cardiac Abnormalities in Youth with Obesity and Type 2 Diabetes.

    PubMed

    Bacha, Fida; Gidding, Samuel S

    2016-07-01

    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 herein provide an overview of the spectrum of early cardiovascular disease manifestation in youth with obesity and type 2 diabetes, in particular abnormalities in cardiac structure and function. Cardiac remodeling and adverse target organ damage is already evident in the pediatric age group in children with obesity and type 2 diabetes. This supports the importance of intensifying obesity prevention efforts and early intervention to treat comorbidities of obesity in the pediatric age group to prevent cardiac events in early adulthood. PMID:27168062

  1. 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. PMID:26163814

  2. [Obesity disease with diabetes mellitus].

    PubMed

    Nagamine, Kazuhiro; Ueno, Hiroaki; Nakazato, Masamitsu

    2015-12-01

    Obesity has been increasing not only in Japan but also in both developed and developing countries. Mean body mass index of Japanese patients with type 2 diabetes has been increasing, and it reached 25.0 in 2013. If body weight decreases more than 3% of initial body weight in patients with metabolic syndrome, not only glucose metabolism but also dyslipidemia and hypertension improve. To reduce the excess body weight, behavior therapy, calorie restriction, and exercise are necessary. The next strategies are drugs including mazindol, glucose-like peptide-1 receptor agonist and sodium-dependent glucose cotransporter 2 inhibitor, and bariatric surgery. Because it is often difficult to reduce body weight using only present non-invasive therapies, clarification of appetite mechanisms and development of novel anti-obesity drugs with few side effects are needed. PMID:26666154

  3. 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

  4. Diabetes in the Aged

    PubMed Central

    Grobin, Wulf

    1970-01-01

    In keeping with the already known high prevalence of diabetes among residents of the Jewish Home for the Aged, Toronto, annual screening disclosed an average incidence of 25.5% of abnormal glucose tolerance (two-hour post-glucose blood sugars above 140 mg./100 ml.) in residents not known to be diabetic. Forty-five (47%) of the 94 residents with abnormal screening values were considered subsequently to be diabetic according to our criteria. Long-term follow-up, particularly of 81 residents initially normoglycemic in 1964-5, confirmed that the natural course of glucose tolerance in this population was one of progressive deterioration. By contrast, improvement amounting to remission has been demonstrated in nine out of 20 residents several years after they had been declared diabetic, and is thought to have been induced by dietotherapy. Moderate hyperglycemia per se did not cause symptoms in these almost always keto-resistant and usually aglycosuric aged diabetics, who often claimed they felt better when hyperglycemic. Hypoglycemia was an ever present danger when anti-diabetic medication was used; it was the main reason for undertreatment. So far, data from our long-term study have not shown morbidity to be markedly increased in the diabetics, and mortality was found to be evenly distributed among diabetic and non-diabetic male residents. However, in the females there was a clear correlation between mortality rate and the diminished glucose tolerance. What may appear as overdiagnosis of diabetes in the aged is recommended in the hope that early institution of dietary treatment will delay the development of clinical diabetes and the need for anti-diabetic agents. This, in turn, would prevent iatrogenic hypoglycemia. It would also reduce the severity and frequency of spontaneous hypoglycemia which, we believe, occurs more commonly in the early phase of diabetes in the aged than is generally realized. PMID:5476778

  5. Stroke prevention in diabetes and obesity.

    PubMed

    Kurukulasuriya, L Romayne; Govindarajan, Gurushankar; Sowers, James

    2006-07-01

    Stroke is an important cause of morbidity and mortality, and is an economic burden. Diabetes and obesity are two important modifiable risk factors for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Risk-factor modification is the most important aspect of prevention of stroke in diabetes and obesity. This includes lifestyle modifications and different therapeutic modalities to control conditions, such as diabetes, hypertension, dyslipidemia and arrhythmia. Recent landmark studies have shown the beneficial effects of statins in diabetic patients even with close to normal or normal low-density lipoprotein cholesterol. Obesity, which is a risk factor for diabetes, hypertension and hyperlipidemia has been shown to be an independent risk factor for stroke. Increased leptin, dysregulation of adipocyte proteins, increased insulin resistance and C-reactive protein may be factors involved in the increased incidence of cardiovascular morbidity and mortality directly related to obesity. Visceral fat is a much bigger health risk than subcutaneous fat. Lifestyle interventions and pharmacotherapeutic agents have been used to manage obesity. In morbidly obese patients, surgical intervention seems to be the best method of treatment with a long-lasting favorable metabolic outcome. In the 21st Century, with the advanced medical knowledge and the therapeutic modalities available, it should be possible to reduce the incidence of stroke associated with diabetes and obesity. PMID:16918267

  6. 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

  7. Family Networks of Obesity and Type 2 Diabetes in Rural Appalachia

    PubMed Central

    Pancoska, Petr; Buch, Shama; Cecchetti, Alfred; Parmanto, Bambang; Vecchio, Marcella; Groark, Stephen; Paulsen, Stephanie; Bardwell, Genevieve; Morton, Cathy; Chester, Ann; Branch, Robert

    2015-01-01

    The prevalence of obesity and diabetes has been studied in adolescent and adult populations in poor, medically underserved rural Appalachia of West Virginia. A web-based questionnaire about obesity and diabetes was obtained in 989 family members of 210 Community Based Clinical Research (CBPR) trained adolescent members of a network of 18 science clubs, incorporating 142 families. After age-correction in <20 years old, 50% of both adolescents and adults were obese. The frequency distribution of obesity was trimodal. In the overall population 10.4% had type 2 diabetes, while 24% of adult, obese subjects had type 2 diabetes. A new metric, the family diabetes risk potential, identified a trimodal distribution of risk potential. In the lowest most common distribution 43% of families had a diabetic family member. In the intermediate distribution, 69% had a diabetic family member, and in the distribution with highest scores all the families had a diabetic member. In conclusion, the poorest counties of rural Appalachia are at crisis level with the prevalence of obesity and diabetes. The distribution of age-corrected obesity and family diabetes risk potential are not normally distributed. We suggest that targeting individual family units at greatest risk offers the most efficient strategy for ameliorating this epidemic. PMID:20443933

  8. Obesity, diabetes, and coronary risk in women.

    PubMed

    Pradhan, Aruna D; Skerrett, Patrick J; Manson, JoAnn E

    2002-12-01

    The latter half of the twentieth century has witnessed rapid advances in cardiovascular epidemiology and medicine. Concurrently, secular trends in lifestyle practices and general improvements in standards of living have resulted in several alarming trends for cardiovascular disease prevention and health promotion. The adoption of unhealthy dietary patterns, growing socio-economic and racial disparities in chronic disease prevalence, low levels of physical activity, and other as yet unidentified genetic and environmental determinants have led to burgeoning rates of both pediatric and adult obesity and diabetes mellitus. Women appear to be at particular risk as the gender advantage for coronary heart disease (CHD) is counterbalanced by an increased incidence of obesity and diabetes. In order to further examine these complex associations, we review the available epidemiological data regarding the impact of obesity and diabetes on cardiovascular health in women. PMID:12478201

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

    PubMed

    Sepehri, Armina; Palazón-Bru, Antonio; 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

  10. 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

  11. 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

  12. [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

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

    PubMed

    Abuyassin, B; Laher, I

    2015-06-01

    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. PMID:26370001

  14. Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring.

    PubMed

    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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. Obesity and type 1 diabetes mellitus management.

    PubMed

    Chillarón, J J; Benaiges, D; Mañé, L; Pedro-Botet, J; Flores Le-Roux, J A

    2015-03-01

    Patients with type 1 diabetes mellitus (T1DM) traditionally had a low body mass index and microangiopathic complications were common. The Diabetes Control and Complications Trial, published in 1993, demonstrated that therapy aimed at maintaining HbA1c levels as close to normal as feasible reduced the incidence of microangiopathy. Since then, the use of intensive insulin therapy to optimise metabolic control became generalised, with two main side effects: a higher rate of severe hypoglycaemia and increased weight gain. Approximately 50% of patients with T1DM are currently obese or overweight, which reduces or nullifies the benefits of good metabolic control, and which has other negative consequences; therefore, strategies to achieve weight control in patients with T1DM are necessary. At present, treatment with GLP-1 and SGLT-2 inhibitors has yielded promising short-term results that need to be confirmed in studies with larger numbers of patients and long-term follow-up. It is possible that, in coming years, the applicability of bariatric surgery in obese patients with T1DM will be similar to that of the general population or T2DM. PMID:25413942

  2. Role of obesity in complicating and confusing the diagnosis and treatment of diabetes in children.

    PubMed

    Jones, Kenneth Lee

    2008-02-01

    The alarming increase in the prevalence of obesity in children in the United States and globally raises major concerns about its future adverse impact on public health. One outcome of this disturbing trend that is already evident is the rapidly increasing incidence of type 2 diabetes at all ages. This disease, once thought to be nonexistent in children, is increasing coincident with obesity. This article addresses the role that obesity plays in type 2 diabetes and also explores its effects on other types of diabetes that occur in childhood. The new challenges for physicians who formulate a differential diagnosis of diabetes in children are discussed. Also examined are modifications of traditional diabetes treatment that can be helpful in combating the insulin resistance associated with obesity and that use medications that are not traditionally used in this age group. Cases are presented to illustrate certain points. An underlying thesis suggests that specific classification may not be as important to the clinician as the understanding of pathophysiologic factors that contribute to hyperglycemia in individual patients. Recommendations are offered to the practitioner for diagnosing and treating the obese child or adolescent with diabetes. PMID:18245428

  3. 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

  4. Lifestyle change and mobility in obese adults with type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adults with type 2 diabetes mellitus often have limitations in mobility that increase with age. An intensive lifestyle intervention that produces weight loss and improves fitness could slow the loss of mobility in such patients. We randomly assigned 5145 overweight or obese adults between the ages o...

  5. 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

  6. 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

  7. Sarcopenic obesity and endocrinal adaptation with age.

    PubMed

    Sakuma, Kunihiro; Yamaguchi, Akihiko

    2013-01-01

    In normal aging, changes in the body composition occur that result in a shift toward decreased muscle mass and increased fat mass. The loss of muscle mass that occurs with aging is termed sarcopenia and is an important cause of frailty, disability, and loss of independence in older adults. Age-related changes in the body composition as well as the increased prevalence of obesity determine a combination of excess weight and reduced muscle mass or strength, recently defined as sarcopenic obesity. Weight gain increases total/abdominal fat, which, in turn, elicits inflammation and fatty infiltration in muscle. Sarcopenic obesity appears to be linked with the upregulation of TNF-α, interleukin (IL)-6, leptin, and myostatin and the downregulation of adiponectin and IL-15. Multiple combined exercise and mild caloric restriction markedly attenuate the symptoms of sarcopenic obesity. Intriguingly, the inhibition of myostatin induced by gene manipulation or neutralizing antibody ameliorates sarcopenic obesity via increased skeletal muscle mass and improved glucose homeostasis. In this review, we describe the possible influence of endocrinal changes with age on sarcopenic obesity. PMID:23690769

  8. 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

  9. [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). PMID:27197110

  10. 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

  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. [Pathological changes in hepatocytes of mice with obesity-induced type 2 diabetes by monosodium glutamate].

    PubMed

    Nakadate, Kazuhiko; Motojima, Kento; Kamata, Sumito; Yoshida, Testuro; Hikita, Masaaki; Wakamatsu, Hisanori

    2014-01-01

    Type 2 diabetes caused by chronic obesity is a major lifestyle-related disease. The present study aimed to determine the pathological changes in hepatocytes in chronic obesity. To develop our type 2 diabetes mouse model, we induced chronic obesity to mice by monosodium glutamate. By overeating, the mice significantly increased their body weight compared with age-matched healthy animals. To analyze the pathological changes in hepatocytes of chronic obesity before preclinical stage of type 2 diabetes, the mice were analyzed by hematoxylin-eosin staining of tissue sections at 15 w of age. In these mice, we observed eosin-negative accumulations of hepatocytes around central veins in the hepatic lobule. By Oil-Red O staining, the eosin-negative granules were identified in the lipid droplets. We then ascertained whether these lipid droplets of hepatocytes in the obese mice could be modified by diet. After 24 h of diet restriction, the lipid droplets of hepatocytes in the obese mice were swollen. Furthermore, after 48 h of the diet restriction, the lipid droplets continued swelling and the autophagy-like structures that were found in the healthy mice under the same condition in the obese mice were not observed. These results suggest that the obese mice might have delayed energy metabolism, which might have influenced the mechanisms of hepatocytes. These findings provide new insight into the functional changes in chronic obesity-induced type 2 diabetes and it is possible that the pathological feature make a contribution to promise the target of pharmacological therapy. PMID:24989474

  15. ASSOCIATION OF OBESITY AND DIABETES WITH SERUM PROSTATE-SPECIFIC ANTIGEN LEVELS IN JAPANESE MALES

    PubMed Central

    NAITO, MARIKO; ASAI, YATAMI; MORI, ATSUYOSHI; FUKADA, YUKO; KUWABARA, MAYUMI; KATASE, SHIRO; HISHIDA, ASAHI; MORITA, EMI; KAWAI, SAYO; OKADA, RIEKO; NISHIO, KAZUKO; TAMAKOSHI, AKIKO; WAKAI, KENJI; HAMAJIMA, NOBUYUKI

    2012-01-01

    ABSTRACT Patients with diabetes have been reported to be at an increased risk for cancers of the pancreas, liver, and colon; however, recent studies have suggested that men with diabetes are at a decreased risk for prostate cancer. Previous studies have found that obese men have lower serum prostate-specific antigen (PSA) concentrations than do non-obese men. Further understanding of how obesity and diabetes affect the PSA concentration may improve our ability to detect clinically relevant prostate tumors. This study examined the relationships among serum PSA level, obesity, and diabetes in apparently healthy Japanese males. We analyzed the baseline data from 2,172 Japanese males (age, 56.8 ± 6.1 years [mean ± SD]) who participated in the Japan Multi-Institutional Collaborative Cohort Study. Diabetes was defined as the presence of both a hemoglobin A1c (JDS) of ≥6.1% and a fasting plasma glucose level of ≥126 mg/dL, or a positive medical history. After adjusting for age, the PSA levels were elevated among males with a higher normal BMI (ranging from 23.0 to 24.9) and lowered among men with a BMI of ≥25.0. In the stratified analysis, these significant differences in BMI categories were absent among diabetics. The mean PSA levels were significantly lower in diabetics than in non-diabetics among subjects aged 60 and over. Our findings suggest that the pre-overweight men had increased PSA levels, and the diabetes was associated with a reduction of PSA levels in elderly. PMID:23092101

  16. The association of gestational weight gain with birth weight in obese pregnant women by obesity class and diabetic status: a population-based historical cohort study.

    PubMed

    Gavard, Jeffrey A; Artal, Raul

    2014-05-01

    Small-for-gestational-age (SGA) and large-for gestational-age (LGA) infants are associated with increased adverse outcomes. While studies have estimated the association of gestational weight gain with birth weight in obese women, estimates are lacking by obesity class and diabetic status. A population-based historical cohort study of 66,010 obese pregnant women in Missouri delivering liveborn, singleton, term infants in 2002–2008 was conducted. Adjusted odds ratios for SGA and LGA infants were calculated for gestational weight gain categories with multiple logistic regression using the revised Institute of Medicine(IOM) recommended 11–20 pounds as the reference group. A weight gain of 3–10 pounds was not significantly associated with an increased risk of an SGA infant compared to 11–20 pounds in 5/6 obesity class/diabetic status combinations.The exception was Class I Obese non-diabetic women(adjusted odds ratio = 1.28, 95 % confidence interval 1.07, 1.52). When lower amounts of weight gain were considered, diabetic women who gained ≤2 pounds (including women who lost weight) did not have a significantly increased risk of an SGA infant compared to diabetic women who gained 11–20 pounds in any obesity class. Weight gains less than 11–20 pounds were significantly associated with a decreased risk of an LGA infant in 5/6 obesity class/diabetic status combinations. Weight gains lower than the IOM recommendation of 11–20 pounds during pregnancy for obese women generally were significantly associated with decreased risk of LGA infants without being significantly associated with increased risk of SGA infants and differed by obesity class and diabetic status. PMID:24077985

  17. Epidemiology of Obesity and Diabetes and Their Cardiovascular Complications.

    PubMed

    Bhupathiraju, Shilpa N; Hu, Frank B

    2016-05-27

    Obesity and diabetes mellitus have reached epidemic proportions in the past few years. During 2011 to 2012, more than one-third of the US population was obese. Although recent trend data indicate that the epidemic has leveled off, prevalence of abdominal obesity continues to rise, especially among adults. As seen for obesity, the past few decades have seen a doubling of the diabetes mellitus incidence with an increasing number of type 2 diabetes mellitus cases being diagnosed in children. Significant racial and ethnic disparities exist in the prevalence and trends of obesity and diabetes mellitus. In general, in both adults and children, non-Hispanic blacks and Mexican Americans seem to be at a high risk than their non-Hispanic white counterparts. Secular changes in agricultural policies, diet, food environment, physical activity, and sleep have all contributed to the upward trends in the diabesity epidemic. Despite marginal improvements in physical activity and the US diet, the food environment has changed drastically to an obesogenic one with increased portion sizes and limited access to healthy food choices especially for disadvantaged populations. Interventions that improve the food environment are critical as both obesity and diabetes mellitus raise the risk of cardiovascular disease by ≈2-fold. Among those with type 2 diabetes mellitus, significant sex differences occur in the risk of cardiovascular disease such that diabetes mellitus completely eliminates or attenuates the advantages of being female. Given the substantial burden of obesity and diabetes mellitus, future research efforts should adopt a translational approach to find sustainable and holistic solutions in preventing these costly diseases. PMID:27230638

  18. Minireview: Epigenetic programming of diabetes and obesity: animal models.

    PubMed

    Seki, Yoshinori; Williams, Lyda; Vuguin, Patricia M; Charron, Maureen J

    2012-03-01

    A growing body of evidence suggests that the intrauterine (IU) environment has a significant and lasting effect on the long-term health of the growing fetus and the development of metabolic disease in later life as put forth in the fetal origins of disease hypothesis. Metabolic diseases have been associated with alterations in the epigenome that occur without changes in the DNA sequence, such as cytosine methylation of DNA, histone posttranslational modifications, and micro-RNA. Animal models of epigenetic modifications secondary to an altered IU milieu are an invaluable tool to study the mechanisms that determine the development of metabolic diseases, such as diabetes and obesity. Rodent and nonlitter bearing animals are good models for the study of disease, because they have similar embryology, anatomy, and physiology to humans. Thus, it is feasible to monitor and modify the IU environment of animal models in order to gain insight into the molecular basis of human metabolic disease pathogenesis. In this review, the database of PubMed was searched for articles published between 1999 and 2011. Key words included epigenetic modifications, IU growth retardation, small for gestational age, animal models, metabolic disease, and obesity. The inclusion criteria used to select studies included animal models of epigenetic modifications during fetal and neonatal development associated with adult metabolic syndrome. Experimental manipulations included: changes in the nutritional status of the pregnant female (calorie-restricted, high-fat, or low-protein diets during pregnancy), as well as the father; interference with placenta function, or uterine blood flow, environmental toxin exposure during pregnancy, as well as dietary modifications during the neonatal (lactation) as well as pubertal period. This review article is focused solely on studies in animal models that demonstrate epigenetic changes that are correlated with manifestation of metabolic disease, including diabetes

  19. Lifestyle change and mobility in obese adults with type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Adults with type 2 diabetes mellitus often have limitations in mobility that increase with age. An intensive lifestyle intervention that produces weight loss and improves fitness could slow the loss of mobility in such patients. Methods We randomly assigned 5145 overweight or obese adults...

  20. 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.

  1. Abdominal Obesity and Brain Atrophy in Type 2 Diabetes Mellitus

    PubMed Central

    Callisaya, Michele; Blizzard, Leigh; Sharman, James E.; Venn, Alison; Phan, Thanh G.; Beare, Richard; Forbes, Josephine; Blackburn, Nicholas B.; Srikanth, Velandai

    2015-01-01

    Aim Type 2 diabetes mellitus (T2D) is associated with gray matter atrophy. Adiposity and physical inactivity are risk factors for T2D and brain atrophy. We studied whether the associations of T2D with total gray matter volume (GMV) and hippocampal volume (HV) are dependent on obesity and physical activity. Materials and Methods In this cross-sectional study, we measured waist-hip ratio (WHR), body mass index (BMI), mean steps/day and brain volumes in a community dwelling cohort of people with and without T2D. Using multivariable linear regression, we examined whether WHR, BMI and physical activity mediated or modified the association between T2D, GMV and HV. Results There were 258 participants with (mean age 67±7 years) and 302 without (mean age 72±7 years) T2D. Adjusting for age, sex and intracranial volume, T2D was independently associated with lower total GMV (p = 0.001) and HV (p<0.001), greater WHR (p<0.001) and BMI (p<0.001), and lower mean steps/day (p = 0.002). After adjusting for covariates, the inclusion of BMI and mean steps/day did not significantly affect the T2D-GMV association, but WHR attenuated it by 32% while remaining independently associated with lower GMV (p<0.01). The T2D-HV association was minimally changed by the addition of BMI, steps/day or WHR in the model. No statistical interactions were observed between T2D and measures of obesity and physical activity in explaining brain volumes. Conclusions Abdominal obesity or its downstream effects may partially mediate the adverse effect of T2D on brain atrophy. This requires confirmation in longitudinal studies. PMID:26560876

  2. Exercise improves cardiac autonomic function in obesity and diabetes.

    PubMed

    Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

    2013-05-01

    Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. PMID:23084034

  3. 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

  4. 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

  5. Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin.

    PubMed

    Katsuda, Yoshiaki; Sasase, Tomohiko; Tadaki, Hironobu; Mera, Yasuko; Motohashi, Yu; Kemmochi, Yusuke; Toyoda, Kaoru; Kakimoto, Kochi; Kume, Shinichi; Ohta, Takeshi

    2015-01-01

    The spontaneously diabetic torii (SDT) fatty rat is a new model of type 2 diabetes showing overt obesity, hyperglycemia and hyperlipidemia. With early onset of diabetes mellitus, diabetic microvascular complications, including nephropathy, peripheral neuropathy and retinopathy, are observed at young ages. In the present study, blood glucose levels of female SDT fatty rats were controlled with phlorizin, a non-selective SGLT inhibitor, to examine whether and how these complications are caused by hyperglycemia. Phlorizin treatment adequately controlled plasma glucose levels during the experiment. At 29 weeks of age, urinary albumin excretion considerably increased in SDT fatty rats. Glomerulosclerosis and tubular pathological findings also indicate diabetic nephropathy. These renal parameters tended to decrease with phlorizin; however, effects were partial. Sciatic nerve conduction velocities were significantly delayed in SDT fatty rats compared with Sprague-Dawley (SD) rats. Intraepidermal nerve fiber density, an indicator of subclinical small nerve fiber neuropathy, significantly decreased in SDT fatty rats. Retinal dysfunction (prolongation of peak latency for oscillatory potential in electroretinograms) and histopathological eye abnormalities, including retinal folding and mature cataracts were also observed. Both nerve and eye disorders were prevented with phlorizin. These findings indicate that severe hyperglycemia mainly causes diabetic complications in SDT fatty rats. However, other factors, such as hyperlipidemia and hypertension, may affect diabetic nephropathy. These characteristics of diabetic complications will become helpful in evaluating new drugs for diabetic complications using SDT fatty rats. PMID:25736710

  6. Mast cell stabilization: novel medication for obesity and diabetes

    PubMed Central

    Wang, Jing; Shi, Guo-Ping

    2012-01-01

    Summary Mast cells are essential in allergic responses and beyond. White adipose tissue from obese humans contains large numbers of mast cells. Serum mast cell tryptase levels are also significantly higher in obese subjects than in lean subjects, suggesting a role of these inflammatory cells in obesity and diabetes. Two types of mast cell-deficient mice, along with corresponding wild-type control mice, were fed a Western diet to induce obesity and diabetes. We also used two anti-allergy drugs, cromolyn and ketotifen (Zaditor), to treat wild-type mice during intake of a Western diet or after the onset of obesity and diabetes, to examine the possible prevention or reversal of these conditions. Mast cell deficiency or pharmacological stabilization reduced body weight gain and improved glucose and insulin sensitivities. These common, side effect-free drugs also reduced pre-established obesity and diabetes without noticeable toxicity. Mechanistic studies suggest that mast cells participate in these metabolic disorders by affecting energy expenditure, protease expression, angiogenesis, apoptosis, and preadipocyte differentiation. These observations open a new era of basic research regarding mast cells, and offer hope to patients suffering from these metabolic disorders. PMID:22069285

  7. Obesity, Diabetes, the Cardiorenal Syndrome, and Risk for Cancer.

    PubMed

    Forte, Victoria; Pandey, Abhishek; Abdelmessih, Rita; Forte, Giovanna; Whaley-Connell, Adam; Sowers, James R; McFarlane, Samy I

    2012-05-01

    Numerous epidemiological studies confirm that the prevalence of obesity and the cardiorenal metabolic syndrome (CRS) is extraordinarily high and that the rates have increased dramatically in the last three decades. In addition, epidemiological data demonstrate that obesity, the CRS, and diabetes are inextricably linked and are all associated with an increased incidence of a number of solid tissue cancers. The mechanisms for this association have been examined, including, but not limited to, higher levels of insulin and free levels of insulin-like growth factor and insulin resistance in obesity and the CRS. Mortality, morbidity, and the associated health care costs which are the link between obesity, the CRS, and diabetes are just beginning to be examined. In addition, we review the advantages of implementing lifestyle and surgical changes to modify obesity, lessening the development of the CRS, diabetes, and associated cancers. Epidemiological data regarding the general mechanisms of the pathogenesis of cancers associated with obesity, the CRS, and diabetes (specifically colon, pancreas, esophageal, liver, breast, prostate, thyroid, and renal carcinomas) are reviewed. The mechanisms by which obesity and other components of the CRS contribute to the pathogenesis of these cancers, such as hormone alterations and insulin- and insulin-like growth factor-dependent pathways of tumor pathogenesis, include the attending roles of inflammation and oxidative stress. Emphasis has been placed on obesity as a modifiable risk factor which, when addressed, provides a reduction in the rate of cancer deaths. In a second part to be published in the next issue of this journal, the relationship between diabetes and cancer will be reviewed in detail. PMID:22851963

  8. Obesity, Diabetes, the Cardiorenal Syndrome, and Risk for Cancer

    PubMed Central

    Forte, Victoria; Pandey, Abhishek; Abdelmessih, Rita; Forte, Giovanna; Whaley-Connell, Adam; Sowers, James R.; McFarlane, Samy I.

    2012-01-01

    Numerous epidemiological studies confirm that the prevalence of obesity and the cardiorenal metabolic syndrome (CRS) is extraordinarily high and that the rates have increased dramatically in the last three decades. In addition, epidemiological data demonstrate that obesity, the CRS, and diabetes are inextricably linked and are all associated with an increased incidence of a number of solid tissue cancers. The mechanisms for this association have been examined, including, but not limited to, higher levels of insulin and free levels of insulin-like growth factor and insulin resistance in obesity and the CRS. Mortality, morbidity, and the associated health care costs which are the link between obesity, the CRS, and diabetes are just beginning to be examined. In addition, we review the advantages of implementing lifestyle and surgical changes to modify obesity, lessening the development of the CRS, diabetes, and associated cancers. Epidemiological data regarding the general mechanisms of the pathogenesis of cancers associated with obesity, the CRS, and diabetes (specifically colon, pancreas, esophageal, liver, breast, prostate, thyroid, and renal carcinomas) are reviewed. The mechanisms by which obesity and other components of the CRS contribute to the pathogenesis of these cancers, such as hormone alterations and insulin- and insulin-like growth factor-dependent pathways of tumor pathogenesis, include the attending roles of inflammation and oxidative stress. Emphasis has been placed on obesity as a modifiable risk factor which, when addressed, provides a reduction in the rate of cancer deaths. In a second part to be published in the next issue of this journal, the relationship between diabetes and cancer will be reviewed in detail. PMID:22851963

  9. 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

  10. Adiposity, Obesity, and Arterial Aging

    PubMed Central

    Shipley, Martin J.; Ahmadi-Abhari, Sara; Tabak, Adam G.; McEniery, Carmel M.; Wilkinson, Ian B.; Marmot, Michael G.; Singh-Manoux, Archana; Kivimaki, Mika

    2015-01-01

    We sought to determine whether adiposity in later midlife is an independent predictor of accelerated stiffening of the aorta. Whitehall II study participants (3789 men; 1383 women) underwent carotid-femoral applanation tonometry at the mean age of 66 and again 4 years later. General adiposity by body mass index, central adiposity by waist circumference and waist:hip ratio, and fat mass percent by body impedance were assessed 5 years before and at baseline. In linear mixed models adjusted for age, sex, ethnicity, and mean arterial pressure, all adiposity measures were associated with aortic stiffening measured as increase in pulse wave velocity (PWV) between baseline and follow-up. The associations were similar in the metabolically healthy and unhealthy, according to Adult Treatment Panel-III criteria excluding waist circumference. C-reactive protein and interleukin-6 levels accounted for part of the longitudinal association between adiposity and PWV change. Adjusting for chronic disease, antihypertensive medication and risk factors, standardized effects of general and central adiposity and fat mass percent on PWV increase (m/s) were similar (0.14, 95% confidence interval: 0.05–0.24, P=0.003; 0.17, 0.08–0.27, P<0.001; 0.14, 0.05–0.22, P=0.002, respectively). Previous adiposity was associated with aortic stiffening independent of change in adiposity, glycaemia, and lipid levels across PWV assessments. We estimated that the body mass index–linked PWV increase will account for 12% of the projected increase in cardiovascular risk because of high body mass index. General and central adiposity in later midlife were strong independent predictors of aortic stiffening. Our findings suggest that adiposity is an important and potentially modifiable determinant of arterial aging. PMID:26056335

  11. 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

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

    PubMed

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

    2016-02-28

    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

  13. Unimolecular Polypharmacy for Treatment of Diabetes and Obesity.

    PubMed

    Tschöp, Matthias H; Finan, Brian; Clemmensen, Christoffer; Gelfanov, Vasily; Perez-Tilve, Diego; Müller, Timo D; DiMarchi, Richard D

    2016-07-12

    Many complex diseases have historically proven to be defiant to the best mono-therapeutic approaches. Several examples of combination therapies have largely overcome such challenges, notably for the treatment of severe hypertension and tuberculosis. Obesity and its consequences, such as type 2 diabetes, have proven to be equally resistant to therapeutic approaches based on single medicines. Proper management of type 2 diabetes often requires adjunctive medications, and the recent registration of a few compound mixtures has set the precedent for combinatorial treatment of obesity. On the other hand, double or triple therapeutic combinations are more difficult to advance to regulatory approval than single molecules. More recently, several classes of novel unimolecular combination therapeutics have emerged with superior efficacy than currently prescribed options and pose the potential to reverse obesity and type 2 diabetes. Here, we summarize the discovery, pre-clinical validation, and first clinical test of such peptide hormone poly-agonist drug candidates. PMID:27411008

  14. Bariatric surgery: an IDF statement for obese Type 2 diabetes

    PubMed Central

    Dixon, J B; Zimmet, P; Alberti, K G; Rubino, F

    2011-01-01

    The International Diabetes Federation Taskforce on Epidemiology and Prevention of Diabetes convened a consensus working group of diabetologists, endocrinologists, surgeons and public health experts to review the appropriate role of surgery and other gastrointestinal interventions in the treatment and prevention of Type 2 diabetes. The specific goals were: to develop practical recommendations for clinicians on patient selection; to identify barriers to surgical access and suggest interventions for health policy changes that ensure equitable access to surgery when indicated; and to identify priorities for research. Bariatric surgery can significantly improve glycaemic control in severely obese patients with Type 2 diabetes. It is an effective, safe and cost-effective therapy for obese Type 2 diabetes. Surgery can be considered an appropriate treatment for people with Type 2 diabetes and obesity not achieving recommended treatment targets with medical therapies, especially in the presence of other major co-morbidities. The procedures must be performed within accepted guidelines and require appropriate multidisciplinary assessment for the procedure, comprehensive patient education and ongoing care, as well as safe and standardized surgical procedures. National guidelines for bariatric surgery need to be developed for people with Type 2 diabetes and a BMI of 35 kg/m2 or more. PMID:21480973

  15. 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

  16. 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. PMID:19594364

  17. Diabetes and ageing-induced vascular inflammation.

    PubMed

    Assar, Mariam El; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2016-04-15

    Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro-inflammatory cytokines, vascular hyperactivation of nuclear factor-кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti-inflammatory microRNAs, and dysfunctional stress-response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co-exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low-grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes-induced vascular impairment in the elderly. PMID:26435167

  18. Obesity and type 2 diabetes: which patients are at risk?

    PubMed

    Garber, A J

    2012-05-01

    An estimated 72.5 million American adults are obese, and the growing US obesity epidemic is responsible for substantial increase in morbidity and mortality, as well as increased health care costs. Obesity results from a combination of personal and societal factors, but is often viewed as a character flaw rather than a medical condition. This leads to stigma and discrimination towards obese individuals and decreases the likelihood of effective intervention. Conditions related to obesity are increasingly common, such as metabolic syndrome, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), all of which indicate high risk for type 2 diabetes (T2DM). This paper reviews the progression from obesity to diabetes, identifying physiological changes that occur along this path as well as opportunities for patient identification and disease prevention. Patients with prediabetes (defined as having IFG, IGT or both) and/or metabolic syndrome require interventions designed to preserve insulin sensitivity and β-cell function, both of which start to deteriorate prior to T2DM diagnosis. Lifestyle modification, including both healthy eating choices and increased physical activity, is essential for weight management and diabetes prevention. Although sustained weight loss is often considered by patients and physicians as being impossible to achieve, effective interventions do exist. Specifically, the Diabetes Prevention Program (DPP) and programs modelled along its parameters have shown repeated successes, even with long-term maintenance. Recent setbacks in the development of medications for weight loss further stress the importance of lifestyle management. By viewing obesity as a metabolic disorder rather than a personal weakness, we can work with patients to address this increasingly prevalent condition and improve long-term health outcomes. PMID:22074144

  19. Prevalence of type 2 diabetes and obesity in rural Mapuche population from Chile.

    PubMed

    Pérez-Bravo, F; Carrasco, E; Santos, J L; Calvillán, M; Larenas, G; Albala, C

    2001-03-01

    The aim of this study was to estimate the prevalence of Type 2 diabetes, impaired glucose tolerance (IGT), and obesity in the Mapuche natives from rural areas in Chile. This cross-sectional study involved men (n = 95) and women (n = 224) older than 20 y from an aboriginal ethnic group (Mapuches), residing in rural communities from the south of Chile. Prevalence of Type 2 diabetes and IGT was calculated according to the World Health Organization criteria. Data on age, degree of ancestral purity, obesity, and hypertension were also obtained. The prevalence of Type 2 diabetes in rural Mapuche natives was estimated as 3.2% (95% CI: 0.7--9.0) in men and 4.5% (95% CI: 2.2--8.1) in women. The overall prevalence of obesity was 56.1% (95% CI: 50.5--61.6): 40.0% (95% CI: 30.1--40.8) in men and 62.9% (95% CI: 56.3--69.3) in women (P value < 0.001). These data suggest that the prevalence of obesity and Type 2 diabetes has been increasing during recent years in the Mapuche communities. The prevalence estimated in this study is higher than that reported 15 y ago. This suggests an important role of lifestyle changes as a possible explanation for epidemiologic transition. PMID:11312066

  20. 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

  1. 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. PMID:26815786

  2. [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

  3. 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...

  4. Contributions of Increasing Obesity and Diabetes to Slowing Decline in Subclinical Coronary Artery Disease

    PubMed Central

    Smith, Carin Y.; Bailey, Kent R.; Emerson, Jane A.; Nemetz, Peter N.; Roger, Véronique L.; Palumbo, Pasquale J.; Edwards, William D.; Leibson, Cynthia L.

    2015-01-01

    Background Our previous study of nonelderly adult decedents with nonnatural (accident, suicide, or homicide) cause of death (96% autopsy rate) between 1981 and 2004 revealed that the decline in subclinical coronary artery disease (CAD) ended in the mid‐1990s. The present study investigated the contributions of trends in obesity and diabetes mellitus to patterns of subclinical CAD and explored whether the end of the decline in CAD persisted. Methods and Results We reviewed provider‐linked medical records for all residents of Olmsted County, Minnesota, who died from nonnatural causes within the age range of 16 to 64 years between 1981 and 2009 and who had CAD graded at autopsy. We estimated trends in CAD risk factors including age, sex, systolic blood pressure, diabetes (qualifying fasting glucose or medication), body mass index, smoking, and diagnosed hyperlipidemia. Using multiple regression, we tested for significant associations between trends in CAD risk factors and CAD grade and assessed the contribution of trends in diabetes and obesity to CAD trends. The 545 autopsied decedents with recorded CAD grade exhibited significant declines between 1981 and 2009 in systolic blood pressure and smoking and significant increases in blood pressure medication, diabetes, and body mass index ≥30 kg/m2. An overall decline in CAD grade between 1981 and 2009 was nonlinear and ended in 1994. Trends in obesity and diabetes contributed to the end of CAD decline. Conclusions Despite continued reductions in smoking and blood pressure values, the previously observed end to the decline in subclinical CAD among nonelderly adult decedents was apparent through 2009, corresponding with increasing obesity and diabetes in that population. PMID:25904589

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. DNA methylation in obesity and type 2 diabetes.

    PubMed

    de Mello, Vanessa Derenji Ferreira; Pulkkinen, Leena; Lalli, Marianne; Kolehmainen, Marjukka; Pihlajamäki, Jussi; Uusitupa, Matti

    2014-05-01

    To elucidate the mechanisms related to the development of type 2 diabetes (T2D) and other degenerative diseases at a molecular level, a better understanding of the changes in the chromatin structure and the corresponding functional changes in molecular pathways is still needed. For example, persons with low birth weight are at a high risk for development of T2D later in life, suggesting that the intrauterine environment contributes to the disease. One of the hypotheses is that epigenetic regulation, including changes in DNA methylation leading to modifications in chromatin structure, are behind metabolic alterations, e.g. leading to the phenomenon termed metabolic memory. Altered DNA methylation has been shown to affect healthy aging and also to promote age-related health problems. There is suggestive evidence that lifestyle changes including weight loss can have an impact on DNA methylation and consequently gene expression. In this review we provide an overview of human studies investigating DNA methylation in obesity and T2D and associated risk factors behind these diseases. PMID:24779963

  11. 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

  12. Epidemiology of hypertension and its relationship with type 2 diabetes and obesity in eastern Morocco.

    PubMed

    Ziyyat, Abderrahim; Ramdani, Noureddine; Bouanani, Nour El Houda; Vanderpas, Jean; Hassani, Benyounès; Boutayeb, Abdeslam; Aziz, Mohammed; Mekhfi, Hassane; Bnouham, Mohammed; Legssyer, Abdelkhaleq

    2014-01-01

    The major objectives of this work are to estimate the hypertension (HT) frequency in the east of Morocco and to study the relationship between HT, type 2 diabetes and obesity. Our sample is composed of 1628 adults aged 40 years and older, recruited voluntarily by using the convenience sampling method through 26 screening campaigns in urban and rural areas of the east of Morocco. We enumerated 516 hypertensive people (31.7%), without significant difference between women (32.5%) and men (30.2%). The known hypertensive people represent 10.1% of the whole sample. The frequency of HT, increases with age and it is more marked in rural (39.9%) than in urban areas (29%) (p < 0.001). It is significantly very high in diabetic subjects (69.9%) than among the non-diabetic ones (27.4%) (p < 0.001). The odd ratio (OR) of the diabetics to HT is 6.16 (IC95% [4.33-8.74]). Among the obese persons, HT is present at (40.8%) vs. (30.2%) among the subjects of normal weight (p < 0.05). The OR of the obese to HT is 1.6 (IC95% [1.26 - 2.04]). In conclusion, our results show a high frequency of HT in the east of Morocco; it affects nearly one third of the adult population aged 40 years and older. The relations between type 2 diabetes and obesity have also been identified and estimated. PMID:25392811

  13. Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age

    PubMed Central

    Murotomi, Kazutoshi; Umeno, Aya; Yasunaga, Mayu; Shichiri, Mototada; Ishida, Noriko; Abe, Hiroko; Yoshida, Yasukazu; Nakajima, Yoshihiro

    2014-01-01

    Tsumura Suzuki Obese Diabetes (TSOD) mouse, a model of obese type 2 diabetes, older than around 11 weeks of age develops diabetic phenotypes. Previous studies have indicated that the development of diabetes is partly due to three loci associated with body weight and glucose homeostasis. However, little is known about the initial events triggering the development of the diabetic phenotypes in TSOD mouse. Here, we investigated the alteration of diabetes-related parameters, including the levels of blood glucose and inflammatory cytokines, and the oxidative stress status, in young TSOD mice. TSOD mice at 5 weeks of age showed increases in body weight and plasma total cholesterol level, but not hyperglycemia or impaired glucose tolerance, compared with age-matched control Tsumura Suzuki Non-Obese (TSNO) mice. Plasma tumor necrosis factor (TNF)-α and interleukin (IL)-6 were not detected in TSOD mice at 5 weeks of age. However, plasma total hydroxyoctadecadienoic acid (tHODE), a biomarker of oxidative stress, was increased in TSOD mice relative to TSNO mice at same age. The results demonstrated that young TSOD mice are exposed to oxidative stress before developing the diabetic phenotypes, and suggested that oxidative stress is an initial event triggering the development of diabetes in TSOD mice. PMID:25411529

  14. 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

  15. Cardiotrophin-1 is inversely associated with obesity in non-diabetic individuals.

    PubMed

    Hung, Hao-Chang; Lu, Feng-Hwa; Wu, Hung-Tsung; Ou, Horng-Yih; Yang, Yi-Ching; Wu, Jin-Shang; Chang, Chih-Jen

    2015-01-01

    Cardiotrophin-1 is known to be a key regulator of energy homeostasis, as well as glucose and lipid metabolism in vivo. However, there are inconsistent results of the association between cardiotrophin-1 and obesity in humans, possibly confounded by hyperglycemia. Therefore, the aim of this study was to investigate the relationships among cardiotrophin-1 levels, overweight and obese individuals without diabetes in a Chinese population. The median (inter-quarter range) serum cardiotrophin-1 levels were 447.9 (230.9, 913.9), 350.6 (201.1, 666.5), and 288.1 (162.3, 572.4) pg/ml in non-diabetic subjects who were of normal weight (n = 522), overweight (n = 203), and obese (n = 93), respectively (trend test p < 0.001). Subjects who were overweight and obese had significantly lower cardiotrophin-1 levels than those with normal weight. The multivariate linear regression analyses showed that overweight (beta = -338.718, 95% CI = -552.786 ~ -124.651, p < 0.01), obese (beta = -530.275, 95% CI = -832.967 ~ -227.583, p < 0.01), and smoking (beta = -377.375, 95% CI = -654.353 ~ -100.397, p < 0.01) were negatively related to cardiotrophin-1 after adjusting for age, gender, HOMA-IR, hypertension, total cholesterol, HDL, triglyceride, eGFR, ALT, and alcohol drinking. The results of this study provided epidemiological evidence that non-diabetic subjects who were overweight or obesity had significantly lower cardiotrophin-1 concentrations than those with normal weight, and both obesity and being overweight were inversely associated with cardiotrophin-1 levels. PMID:26621340

  16. Pregnancy after diabetes obesity surgery (PADOS): Incidence and outcomes.

    PubMed

    Whyte, M; Pring, C; Cooke, D; Hart, K; McGowan, B M; Subramanian, D; Shawe, J

    2014-07-01

    Half of all bariatric surgical procedures are in women of childbearing age but it remains unclear whether surgery is suitable for women who subsequently conceive: specifically the relative risks and benefits of potential nutrient deficiencies versus weight reduction. We will present data collected from Clinical Practice Research Databases on the maternal and fetal outcomes of pregnancies complicated either by obesity or previous bariatric surgery (BS). Two groups, matched to obese controls for BMI pre-BS and post-BS (at the time of ante-natal booking) will be compared. In this way, the effect of BS on pregnancy outcomes may be examined, independent of its effect on weight. A sub-group of women with antecedent Type 2 diabetes (T2DM) will allow for investigation of the additional impact and persistence of this co-morbidity. This builds upon pilot data collected from a retrospective cohort of women (18-45years) undergoing laparoscopic roux-en-Y (RYGB) surgery over a 24-month period (n=218). After exclusions and loss to follow up, data from 111 patients were analysed; 81 (73%) had conceived prior to RYGB, 20 (18%) became pregnant post RYGB and a further 22 patients (20%) were trying to conceive at the time of data collection. Three women had T2DM which resolved post BS. A suggestion of greater miscarriage risk prior to surgery in this sub-group will be confirmed as more women are recruited. Pregnancy is a frequent desire/occurrence after BS. This database study will advance understanding of the maternal and fetal outcomes of such pregnancies and inform antenatal care. PMID:26104634

  17. Regardless of central obesity, metabolic syndrome is a significant predictor of type 2 diabetes in Japanese Americans

    PubMed Central

    Sakashita, Yu; Nakanishi, Shuhei; Yoneda, Masayasu; Nakashima, Reiko; Yamane, Kiminori; Kohno, Nobuoki

    2015-01-01

    Aims/Introduction The impact of metabolic syndrome (MetS) on the development of type 2 diabetes has been reported in different ethnic populations. However, whether central obesity is an essential component as a diagnostic criterion for MetS remains a controversial topic. The aim of the present study was to investigate the association between MetS and the incidence of type 2 diabetes with or without central obesity in a Japanese American population. Materials and Methods We examined whether MetS predicts incident type 2 diabetes among 928 Japanese American participants who did not have diabetes enrolled in an ongoing medical survey between 1992 and 2007. MetS was defined on the basis of American Heart Association/National Heart, Lung, and Blood Institute criteria. The average follow-up period was approximately 6.8 years. Results During the follow-up period, 116 new cases of diabetes were diagnosed. Compared to the participants without MetS, the hazard ratio (HR) for incident type 2 diabetes was significantly higher in participants with MetS, after adjustment for sex, age and impaired glucose tolerance (HR 1.64, 95% CI 1.11–2.42). The risk of type 2 diabetes was found to be significantly higher in participants with MetS but without central obesity (HR 2.07, 95% CI 1.25–3.41), as well as in participants with MetS and with central obesity (HR 2.46, 95% CI 1.51–4.01) than in participants with neither MetS nor central obesity, after adjustment for sex, age and impaired glucose tolerance. Conclusions These results show that the presence of MetS, with or without central obesity, could independently predict the development of type 2 diabetes in Japanese Americans. PMID:26417409

  18. Obesity, diabetes and atrial fibrillation; epidemiology, mechanisms and interventions.

    PubMed

    Asghar, O; Alam, U; Hayat, S A; Aghamohammadzadeh, R; Heagerty, A M; Malik, R A

    2012-11-01

    The last few decades have witnessed a global rise in adult obesity of epidemic proportions. The potential impact of this is emphasized when one considers that body mass index (BMI) is a powerful predictor of death, type 2 diabetes (T2DM) and cardiovascular (CV) morbidity and mortality [1, 2]. Similarly we have witnessed a parallel rise in the incidence of atrial fibrillation (AF), the commonest sustained cardiac arrhythmia, which is also a significant cause of cardiovascular morbidity and mortality. Part of this increase is attributable to advances in the treatment of coronary heart disease (CHD) and heart failure (HF) improving life expectancy and consequently the prevalence of AF. However, epidemiological studies have demonstrated an independent association between obesity and AF, possibly reflecting common pathophysiology and risk factors for both conditions. Indeed, weight gain and obesity are associated with structural and functional changes of the cardiovascular system including left atrial and ventricular remodeling, haemodynamic alterations, autonomic dysfunction, and diastolic dysfunction. Moreover, diabetic cardiomyopathy is characterized by an adverse structural and functional cardiac phenotype which may predispose to the development of AF [3]. In this review, we discuss the pathophysiological and mechanistic relationships between obesity, diabetes and AF, and the challenges posed in the management of this high-risk group of individuals. PMID:22920475

  19. Obesity, Diabetes and Atrial Fibrillation; Epidemiology, Mechanisms and Interventions

    PubMed Central

    Asghar, O; Alam, U; Hayat, SA; Aghamohammadzadeh, R; Heagerty, AM; Malik, RA

    2012-01-01

    The last few decades have witnessed a global rise in adult obesity of epidemic proportions. The potential impact of this is emphasized when one considers that body mass index (BMI) is a powerful predictor of death, type 2 diabetes (T2DM) and cardiovascular (CV) morbidity and mortality [1, 2]. Similarly we have witnessed a parallel rise in the incidence of atrial fibrillation (AF), the commonest sustained cardiac arrhythmia, which is also a significant cause of cardiovascular morbidity and mortality. Part of this increase is attributable to advances in the treatment of coronary heart disease (CHD) and heart failure (HF) improving life expectancy and consequently the prevalence of AF. However, epidemiological studies have demonstrated an independent association between obesity and AF, possibly reflecting common pathophysiology and risk factors for both conditions. Indeed, weight gain and obesity are associated with structural and functional changes of the cardiovascular system including left atrial and ventricular remodeling, haemodynamic alterations, autonomic dysfunction, and diastolic dysfunction. Moreover, diabetic cardiomyopathy is characterized by an adverse structural and functional cardiac phenotype which may predispose to the development of AF [3]. In this review, we discuss the pathophysiological and mechanistic relationships between obesity, diabetes and AF, and the challenges posed in the management of this high-risk group of individuals. PMID:22920475

  20. A teleological view of obesity, diabetes and hypertension.

    PubMed

    Landsberg, Lewis

    2006-09-01

    1. The current worldwide epidemic of obesity and its major complications, namely type 2 diabetes and hypertension, is well documented. The present mini-review develops the thesis that 'thrifty' metabolic traits, evolved in the setting of intermittent famine, contribute to the obesity pandemic. 2. These thrifty traits, namely a decreased capacity for dietary thermogenesis and an increased resistance to insulin-mediated glucose uptake in skeletal muscle, would prolong survival during famine but predispose to obesity and diabetes in the face of abundance. The regulation of dietary thermogenesis by the sympathetic nervous system also explains the well-established association between obesity and high blood pressure. 3. These observations provide a deep-seated rationale for the efficacy of lifestyle interventions in the treatment of obesity and its complications and may also provide a predicate for the development of new therapeutic strategies aimed at neutralizing the impact of these thrifty traits. Such strategies may entail, for example, therapeutic agents that enhance metabolic rate during low-energy diets, thereby reversing the physiological impediment imposed by suppression of the sympathetic nervous system. PMID:16922822

  1. 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. PMID:25960181

  2. 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

  3. Congener-specific polychlorinated biphenyls and the prevalence of diabetes in the Saku Control Obesity Program (SCOP).

    PubMed

    Tanaka, Takahisa; Morita, Akemi; Kato, Masayuki; Hirai, Tetsuya; Mizoue, Tetsuya; Terauchi, Yasuo; Watanabe, Shaw; Noda, Mitsuhiko

    2011-01-01

    The prevalence of diabetes is increasing globally. In addition to established risk factors for diabetes, such as diet, inactivity, overweight and obesity, the involvement of persistent organic pollutants, including dioxins and polychlorinated biphenyls (PCBs), has also been suggested to be a possible, but controversial, cause of this epidemic. The present study investigated the association between blood PCB congener levels and the prevalence of diabetes among middle-aged, overweight and obese Japanese participants in the Saku Control Obesity Program. One hundred seventeen participants had their congener-specific PCB levels measured in addition to undergoing routine blood analyses at the time of a medical checkup. Prevalent diabetes was defined according to two methods: definite diabetes was defined as people with an HbA1c level ≥ 6.9% or who were taking medication for diabetes, and all diabetes was defined as people with an HbA1c level ≥ 6.5%, a fasting plasma glucose level ≥ 126 mg/dL, or a history of doctor-diagnosed diabetes. A multiple logistic regression analysis was performed to analyze the association between the PCB levels and the prevalence of diabetes, with adjustments for sex, age, body mass index and total lipids. As a result, PCB 146 and 180 were positively associated and PCB 163/164 and 170 were negatively associated with the prevalence of definite diabetes. The significance of the association of PCB 180 and 163/164 with the prevalence of diabetes persisted regardless of the definition of diabetes or adjustments for total lipids, suggesting the possibility that these parameters may modify the risk of diabetes. PMID:21551956

  4. 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

  5. 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

  6. Lipotoxicity in obesity and diabetes-related cardiac dysfunction.

    PubMed

    Zlobine, Igor; Gopal, Keshav; Ussher, John R

    2016-10-01

    Patients with type 2 diabetes (T2D) are at increased risk for cardiovascular diseases including diabetic cardiomyopathy, which is ventricular dysfunction independent of underlying coronary artery disease and/or hypertension. With numerous advancements in our ability to detect ventricular dysfunction, as well as the molecular mechanisms contributing to ventricular dysfunction in diabetic patients, it is now appreciated that diabetic cardiomyopathy is becoming more prevalent in our population. In spite of these advancements, we do not have any specific therapies currently approved for treating this condition. As obesity increases the risk for both T2D and cardiovascular disease, it has been postulated that obesity-mediated alterations in myocardial lipid metabolism are critical to the pathophysiology of diabetic cardiomyopathy. Indeed, animal studies have provided strong evidence that alterations in either myocardial fatty acid uptake or fatty acid β-oxidation lead to the accumulation of various lipid intermediates including triacylglycerol, diacylglycerol, ceramide, long-chain acyl CoA, acylcarnitine, and many others that are tightly linked to the progression of ventricular dysfunction. We review herein why lipid intermediates accumulate in the heart during obesity and/or T2D, with a focus on which of these various lipid intermediates may be responsible for cardiac lipotoxicity, and whether findings in animal models are relevant to humans. An improved understanding of how these lipid intermediates accumulate in the heart and how they produce cardiac toxicity may lead to the discovery of novel targets to pursue for the treatment of human diabetic cardiomyopathy. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26899197

  7. Aging, Resistance Training, and Diabetes Prevention

    PubMed Central

    Flack, Kyle D.; Davy, Kevin P.; Hulver, Matthew W.; Winett, Richard A.; Frisard, Madlyn I.; Davy, Brenda M.

    2011-01-01

    With the aging of the baby-boom generation and increases in life expectancy, the American population is growing older. Aging is associated with adverse changes in glucose tolerance and increased risk of diabetes; the increasing prevalence of diabetes among older adults suggests a clear need for effective diabetes prevention approaches for this population. The purpose of paper is to review what is known about changes in glucose tolerance with advancing age and the potential utility of resistance training (RT) as an intervention to prevent diabetes among middle-aged and older adults. Age-related factors contributing to glucose intolerance, which may be improved with RT, include improvements in insulin signaling defects, reductions in tumor necrosis factor-α, increases in adiponectin and insulin-like growth factor-1 concentrations, and reductions in total and abdominal visceral fat. Current RT recommendations and future areas for investigation are presented. PMID:21197110

  8. 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. PMID:25312902

  9. Intrauterine diabetic environment confers risks for type 2 diabetes mellitus and obesity in the offspring, in addition to genetic susceptibility.

    PubMed

    Dabelea, D; Pettitt, D J

    2001-01-01

    Numerous studies have reported that offspring whose mothers had type 2 diabetes mellitus (DM) are more likely to develop type 2 DM, impaired glucose tolerance, and obesity at an early age than offspring whose fathers had DM. Exposure to the diabetic intrauterine environment has been shown to be an important risk factor for all these conditions. To what extent transmission of type 2 DM from mother to offspring is the effect of genetic inheritance and to what extent it is the long-term consequence of exposure to maternal hyperglycemia is still uncertain. There are, of course, interactions between the diabetic intrauterine environment and genetics. Several data in experimental animals as well as in humans suggest, however, that exposure of the fetus to the mother's DM confers a risk for type 2 DM and obesity that is above any genetically transmitted susceptibility. In the Pima Indian population much of the increase in childhood type 2 DM can be attributed to the diabetic intrauterine environment. This suggests that intensive glucose control during pregnancy might have extended beneficial effects, contributing to a decrease in the prevalence of childhood type 2 DM. PMID:11592564

  10. 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

  11. 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

  12. 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

  13. Investigating health and diabetes perceptions among Hmong American children, 9-18 years of age.

    PubMed

    Mulasi-Pokhriyal, Urvashi; Smith, Chery

    2011-06-01

    After immigrating to the United States (US), obesity and diabetes have increased among the Hmong. Therefore, this study investigated how Hmong children perceive health and diabetes risk so that appropriate interventions may be planned. Hmong children (N = 335), ages 9-18 years participated in this study. A survey used Social Cognitive Theory (SCT) as the theoretical framework and silhouette drawing instrument. Heights and weights were measured and body mass indexes (BMIs) were calculated. About half of the children were either overweight (BMI ≥ 85th < 95th percentile) or obese (BMI ≥ 95th percentile). About 75% chose average sized silhouettes as healthiest and heaviest silhouettes as diabetic shape. Environmental influences including food availability, parents, and media influenced children's health perceptions. Results suggest a need for culturally appropriate interventions, aiming towards a child's environment and educating them about risks associated with obesity and diabetes. PMID:20686849

  14. A SYSTEMATIC REVIEW OF OVERWEIGHT, OBESITY, AND TYPE 2 DIABETES AMONG ASIAN AMERICAN SUBGROUPS

    PubMed Central

    STAIMEZ, LISA R.; WEBER, MARY BETH; NARAYAN, K.M. VENKAT; OZA-FRANK, REENA

    2015-01-01

    This systematic review synthesizes data published between 1988 and 2009 on mean BMI and prevalence of overweight, obesity, and type 2 diabetes among Asian subgroups in the U.S. We conducted systematic searches in PubMed for peer-reviewed, English-language citations that reported mean BMI and percent overweight, obesity, and diabetes among South Asians/Asian Indians, Chinese, Filipinos, Koreans, and Vietnamese. We identified 647 database citations and 23 additional citations from hand-searching. After screening titles, abstracts, and full-text publications, 97 citations remained. None were published between 1988 and 1992, 28 between 1993 and 2003, and 69 between 2004 and 2009. Publications were identified for the following Asian subgroups: South Asian (n=8), Asian Indian (n=20), Chinese (n=44), Filipino (n=22), Korean (n= 8), and Vietnamese (n=3). The observed sample sizes ranged from 32 to 4245 subjects with mean ages from 24 to 78 years. Among samples of men and women, the lowest reported mean BMI was in South Asians (22.1 kg/m2), and the highest was in Filipinos (26.8 kg/m2). Estimates for overweight (12.8 - 46.7%) and obesity (2.1 – 59.0%) were variable. Among men and women, the highest rate of diabetes was reported in Asian Indians with BMI ≥ 30 kg/m2 (32.9%, age and sex standardized). This review suggests heterogeneity among U.S. Asian populations in cardiometabolic risk factors, yet comparisons are limited due to variability in study populations, methods, and definitions used in published reports. Future efforts should adopt standardized methods to understand overweight, obesity and diabetes in this growing U.S. ethnic population. PMID:23590534

  15. A systematic review of overweight, obesity, and type 2 diabetes among Asian American subgroups.

    PubMed

    Staimez, Lisa R; Weber, Mary Beth; Narayan, K M Venkat; Oza-Frank, Reena

    2013-07-01

    This systematic review synthesizes data published between 1988 and 2009 on mean BMI and prevalence of overweight, obesity, and type 2 diabetes among Asian subgroups in the U.S. We conducted systematic searches in Pub- Med for peer-reviewed, English-language citations that reported mean BMI and percent overweight, obesity, and diabetes among South Asians/Asian Indians, Chinese, Filipinos, Koreans, and Vietnamese. We identified 647 database citations and 23 additional citations from hand-searching. After screening titles, abstracts, and full-text publications, 97 citations remained. None were published between 1988 and 1992, 28 between 1993 and 2003, and 69 between 2004 and 2009. Publications were identified for the following Asian subgroups: South Asian (n=8), Asian Indian (n=20), Chinese (n=44), Filipino (n=22), Korean (n= 8), and Vietnamese (n=3). The observed sample sizes ranged from 32 to 4245 subjects with mean ages from 24 to 78 years. Among samples of men and women, the lowest reported mean BMI was in South Asians (22.1 kg/m(2)), and the highest was in Filipinos (26.8 kg/m(2)). Estimates for overweight (12.8-46.7%) and obesity (2.1-59.0%) were variable. Among men and women, the highest rate of diabetes was reported in Asian Indians with BMI ≥ 30 kg/m(2) (32.9%, age and sex standardized). This review suggests heterogeneity among U.S. Asian populations in cardiometabolic risk factors, yet comparisons are limited due to variability in study populations, methods, and definitions used in published reports. Future efforts should adopt standardized methods to understand overweight, obesity and diabetes in this growing U.S. ethnic population. PMID:23590534

  16. 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

  17. 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

    Koo, Bo Kyung; Moon, Min Kyong

    2016-06-01

    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

  18. Prevalence of Obesity was Related to HLA-DQ in 2–4 Year Old Children at Genetic Risk for Type 1 Diabetes

    PubMed Central

    Yang, Jimin; Lernmark, Åke; Uusitalo, Ulla M.; Lynch, Kristian F.; Veijola, Riitta; Winkler, Christiane; Larsson, Helena Elding; Rewers, Marian; She, Jin-Xiong; Ziegler, Anette G.; Simell, Olli G.; Hagopian, William A.; Akolkar, Beena; Krischer, Jeffrey P.; Vehik, Kendra

    2014-01-01

    OBJECTIVES Body size is postulated to modulate type 1 diabetes as either a trigger of islet autoimmunity or an accelerator to clinical onset after seroconversion. As overweight and obesity continue to rise among children, the aim of this study was to determine whether human leukocyte antigen DQ (HLA-DQ) genotypes may be related to body size among children genetically at risk for type 1 diabetes. METHODS Repeated measures of weight and height were collected from 5 969 children 2–4 years of age enrolled in The Environmental Determinants of Diabetes in the Young prospective study. Overweight and obesity was determined by the International Obesity Task Force cutoff values that correspond to body mass index of 25 and 30 kg/m2 at age 18. RESULTS The average BMI was comparable across specific HLA genotypes at every age point. The proportion of overweight was not different by HLA, but percent obesity varied by age with a decreasing trend among DQ2/8 carriers (p for trend = 0.0315). A multivariable regression model suggested DQ2/2 was associated with higher obesity risk at age four (OR, 2.41; 95% CI, 1.21–4.80) after adjusting for the development of islet autoantibody and/or type 1 diabetes. CONCLUSIONS The HLA-DQ2/2 genotype may predispose to obesity among 2–4 year old children with genetic risk for type 1 diabetes. PMID:24694666

  19. 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

  20. 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

  1. 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

  2. Overweight and Obesity in Youth With Type 1 Diabetes

    PubMed Central

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

    2014-01-01

    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. PMID:24894137

  3. Microalbuminuria in Obese Young and Middle Aged Population: A Potential Marker of Cardiovascular Risk.

    PubMed

    Purohit, Purvi; Garg, Kunal; Singh, Vikram; Dwivedi, Shailendra; Sharma, Praveen

    2016-07-01

    Microalbuminuria is an established cardiovascular risk indicator in diabetes, hypertension and the general population. There is lack of information on MAU in healthy obese Indian adults and an ongoing debate whether obese adults deserve targeted identification and clinical intervention for MAU and prediabetes. We aimed to screen the healthy obese, young (group I) and middle aged (group II) adults for prevalence of MAU and prediabetes and study its association with Framingham risk score. The study included 50 healthy obese young (20-30 years) and middle aged adults (31-50 years), attending the outpatient clinic of Dept. of Medicine for a duration of 2 months (July-August). The patients were screened for fasting blood sugar, lipid profile and MAU. Of the total patients 28 % had MAU, 32.14 % of which had prediabetes and 33.33 % had diabetes whereas 10 % were normoglycemic. The group I patients had 50 % cases of MAU and group II had 25 % patients with MAU. Group II 63.63 % pre-diabetics. The values of MAU obtained were correlated with age, gender, body mass index, systolic and diastolic blood pressure, FBS, waist to hip ratio using Pearson's Coefficient (p < 0.05). The 10 year CVD risk calculated using FRS in subjects with MAU was higher as compared to those without MAU. Thus we conclude that Indian, young and middle aged obese adults to be at a risk of prediabetes, MAU and CV risk warranting their routine screening for better clinical outcomes. PMID:27382209

  4. 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

  5. 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

  6. 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

  7. [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

  8. Obesity, diabetes and cancer: insight into the relationship from a cohort with growth hormone receptor deficiency.

    PubMed

    Guevara-Aguirre, Jaime; Rosenbloom, Arlan L

    2015-01-01

    Obesity with insulin-resistant diabetes and increased cancer risk is a global problem. We consider the alterations of metabolism attendant on the underlying pathogenic overnutrition and the role of the growth hormone (GH)-IGF-1 axis in this interaction. Obesity-induced insulin resistance is a determinant of diabetes. Excess glucose, and an elevated concentration of insulin acting through its own receptors along with complex interactions with the IGF-1 system, will add extra fuel and fuel signalling for malignant growth and induce anti-apoptotic activities, permitting proliferation of forbidden clones. In Ecuador there are ~100 living adults with lifelong IGF-1 deficiency caused by a GH receptor (GHR) mutation who, despite a high percentage of body fat, have markedly increased insulin sensitivity compared with age- and BMI-matched control relatives, and no instances of diabetes, which is present in 6% of unaffected relatives. Only 1 of 20 deceased individuals with GHR deficiency died of cancer vs 20% of ~1,500 relatives. Fewer DNA breaks and increased apoptosis occurred in cell cultures exposed to oxidant agents following addition of serum from GHR-deficient individuals vs serum from control relatives. These changes were reversible by adding IGF-1 to the serum from the GHR-deficient individuals. The reduction in central regulators of pro-ageing signalling thus appears to be the result of an absence of GHR function. The complex inter-relationship of obesity, diabetes and cancer risk is related to excess insulin and fuel supply, in the presence of heightened anti-apoptosis and uninhibited DNA damage when GHR function is normal. PMID:25316432

  9. 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

  10. 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,…

  11. Pharmacogenomics of cardiovascular complications in diabetes and obesity

    PubMed Central

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

    2015-01-01

    Heart disease is major cause of death for population in US and worldwide. The complex interplay of the mechanisms between diabetes, obesity, inflammation causes concerns for therapeutic understanding and developing treatment options for patient. 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 benefit. Pharmacogenomics is the scientific basis which offers the fundamental understanding for disease 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 enables 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

  12. The oral microflora in obesity and type-2 diabetes

    PubMed Central

    Shillitoe, Edward; Weinstock, Ruth; Kim, Taewan; Simon, Howard; Planer, Jessica; Noonan, Susan; Cooney, Robert

    2012-01-01

    Background Type 2 diabetes mellitus (T2DM) is prevalent in people with obesity. It has been proposed that these conditions are related to specific features of the microflora of the mouth and lower gastrointestinal (GI) tract. Hyperglycemia often resolves quickly after Roux-en-Y gastric bypass (RYGB) but the role of the GI microflora cannot be examined easily because of reduced intestinal mobility. We propose that the study of microorganisms present in the mouth of patients undergoing RYGB will contribute to our understanding of the role of bacteria in the pathogenesis of T2DM. Objective To conduct a feasibility study to examine differences in oral microbes in obese patients with and without T2DM and to determine whether it is feasible to measure changes after gastric bypass surgery. Methods Individuals with morbid obesity (n=29), of whom 13 had T2DM, were studied. Oral rinses, stool samples, and blood samples were obtained before RYGB, and oral rinses and blood samples were obtained at 2 and 12 weeks postsurgery. Results Prior to surgery, participants with T2DM had slightly higher total levels of oral bacteria than those without diabetes. Those with HbA1c > 6.5% had rather lower levels of Bifidobacteria in the mouth and stool. At 2 weeks post-RYGB, patients with T2DM were able to reduce or discontinue their hypoglycemic medications. Stool samples could not be obtained but oral rinses were readily available. The levels of oral Bifidobacteria had increased tenfold and levels of circulating endotoxin and tumor necrosis factor-alpha had decreased. Conclusions The study of oral bacteria before and after RYGB is feasible and should be tested in larger patient populations to increase our understanding of the role of microorganisms in the pathogenesis of obesity and T2DM. PMID:23119124

  13. 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

  14. Metformin versus Placebo in Obese Pregnant Women without Diabetes.

    PubMed

    Sahin, Mustafa; Corapcioglu, Demet

    2016-06-23

    To the Editor: Syngelaki et al. (Feb. 4 issue)(1) describe the efficacy of metformin in reducing gestational weight gain in women with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35. Although their study does not show a reduction in the neonatal birth weight, their results underscore the ability of metformin to reduce gestational weight gain in women with moderate-to-severe obesity without diabetes. One question is whether the exclusion of patients who were started on insulin after the oral glucose-tolerance test would alter the results of the study. . . . PMID:27332919

  15. Metformin versus Placebo in Obese Pregnant Women without Diabetes.

    PubMed

    Stanford, Fatima C; Alfaris, Nasreen; Misra, Madhusmita

    2016-06-23

    To the Editor: Syngelaki et al. (Feb. 4 issue)(1) describe the efficacy of metformin in reducing gestational weight gain in women with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35. Although their study does not show a reduction in the neonatal birth weight, their results underscore the ability of metformin to reduce gestational weight gain in women with moderate-to-severe obesity without diabetes. One question is whether the exclusion of patients who were started on insulin after the oral glucose-tolerance test would alter the results of the study. . . . PMID:27332918

  16. Metformin versus Placebo in Obese Pregnant Women without Diabetes.

    PubMed

    2016-06-23

    To the Editor: Syngelaki et al. (Feb. 4 issue)(1) describe the efficacy of metformin in reducing gestational weight gain in women with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35. Although their study does not show a reduction in the neonatal birth weight, their results underscore the ability of metformin to reduce gestational weight gain in women with moderate-to-severe obesity without diabetes. One question is whether the exclusion of patients who were started on insulin after the oral glucose-tolerance test would alter the results of the study. . . . PMID:27332917

  17. [Impact of maternal obesity and diabetes on placental function].

    PubMed

    Gabory, Anne; Chavatte-Palmer, Pascale; Vambergue, Anne; Tarrade, Anne

    2016-01-01

    Located at the feto-maternal interface, the placenta is involved in exchange, endocrine and immune functions, which impact fetal development. In contact with the maternal environment, this organ is sensitive to metabolic disorders as over-nutrition, obesity or diabetes. The alteration of blood parameters associated with these pathologies affects placental histology, vascularization and nutrient transfers and, according to the types of troubles, induces local inflammation or hypoxia. These placental changes lead to disturbance of development and fetal growth, which increase the risk of pathologies in offspring in adulthood. The placenta thus appears as a crucial player in the fetal programming. PMID:26850609

  18. Diabetes and Cardiovascular Disease Outcomes in the Metabolically Healthy Obese Phenotype

    PubMed Central

    Appleton, Sarah L.; Seaborn, Christopher J.; Visvanathan, Renuka; Hill, Catherine L.; Gill, Tiffany K.; Taylor, Anne W.; Adams, Robert J.

    2013-01-01

    OBJECTIVE To determine the correlates of the “metabolically healthy obese” (MHO) phenotype and the longitudinal risks of diabetes and cardiovascular disease (CVD)/stroke associated with this phenotype. RESEARCH DESIGN AND METHODS The North West Adelaide Health Study is a prospective cohort study of 4,056 randomly selected adults aged ≥18 years. Participants free of CVD/stroke and not underweight (n = 3,743) were stratified by BMI categories and metabolic risk, defined as having two or more International Diabetes Federation metabolic syndrome criteria, excluding waist circumference. RESULTS Correlates of the MHO (n = 454 [12.1%]) included smoking, socioeconomic disadvantage, and physical inactivity. Compared with metabolically healthy normal-weight subjects (n = 1,172 [31.3%]), the MHO were more likely to develop metabolic risk (15.5 vs. 33.1%, P < 0.001) and incident diabetes (odds ratio 2.09 [95% CI 0.87–5.03]) but not CVD/stroke (1.16 [0.58–2.29]) during 5.5–10.3 years of follow-up. These risks were not seen in MHO subjects maintaining metabolic health (n = 188 [67%]). Sustained metabolic health in obese participants was associated with age ≤40 years and lower waist circumference. Compared with the metabolically at-risk obese, MHO women demonstrated a significantly higher (mean [SE]) percentage of leg fat (49.9 [0.5] vs. 53.2 [0.7]) and lower waist circumference (104 [0.6] vs. 101 cm [0.8]), despite no significant differences in overall adiposity. CONCLUSIONS “Healthy” obesity was a transient state for one-third of subjects. Persistence of a MHO phenotype, which was associated with favorable outcomes, was related to younger age and a more peripheral fat distribution. The MHO phenotype may be sustained by promoting lower waist circumferences. PMID:23491523

  19. 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

  20. Risk of the Development of Diabetes and Cardiovascular Disease in Metabolically Healthy Obese People

    PubMed Central

    Kim, Nan Hee; Seo, Ji A; Cho, Hyunjoo; Seo, Ji Hye; Yu, Ji Hee; Yoo, Hye Jin; Kim, Sin Gon; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop; Shin, Chol; Cho, Nam Han

    2016-01-01

    Abstract The reported effects of a metabolically healthy obese (MHO) phenotype on diabetes and cardiovascular disease (CVD) risk are contradictory. Within the context of a population-based cohort study, we aimed to investigate the long-term risk of an MHO status for the development of diabetes and CVD, and whether consistency of this phenotype or age affected cardiometabolic outcomes. We recruited 7588 subjects without diabetes or CVD, aged 40 to 69 years at baseline examination, from the Korean Genome and Epidemiology Study, and followed-up these subjects for 10 years biennially. Participants were divided into 4 groups based on the body mass index and the presence of metabolic syndrome: metabolically healthy normal weight (MHNW), MHO, metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). We defined persistent phenotypes if subjects maintained the same phenotype at every visit from baseline to their last visit. Incident diabetes and CVD morbidity or mortality were identified during 10 years of follow-up. Compared to MHNW controls, MUNW and MUO groups had increased risk for development of diabetes (hazard ratio [HR] 3.0 [95% CI: 2.5–3.6], and 4.0 [3.4–4.7], respectively) and CVD (HR 1.6 [1.3–2.0], and 1.9 [1.5–2.4], respectively). However, the MHO group showed only a marginal increase in risk for diabetes and CVD (HR 1.2 [0.99–1.6], 1.4 [0.99–1.8], respectively). The impact of MHO on the development of diabetes was more prominent in younger individuals (HR 1.9 [1.2–3.1] vs 1.1 [0.8–1.4], <45 years vs ≥45 years at baseline). Only 15.8% of MHO subjects maintained the MHO phenotype at every visit from baseline to the 5th biennial examination (persistent MHO). In subjects with persistent MHO, the risk for diabetes and CVD was significantly higher than those with persistent MHNW (1.9 [1.2–3.1], 2.1 [1.2–3.7], respectively). MHO phenotype, even if maintained for a long time, was associated with a significantly higher

  1. IGF-binding protein 1 and abdominal obesity in the development of type 2 diabetes in women

    PubMed Central

    Lewitt, Moira S; Hilding, Agneta; Brismar, Kerstin; Efendic, Suad; Östenson, Claes-Göran; Hall, Kerstin

    2010-01-01

    Objective Low levels of IGF-binding protein 1 (IGFBP1) are associated with metabolic syndrome and predict diabetes development in men. The aim of this study was to determine the levels of IGFBP1 in women who later develop diabetes, in relation to abdominal obesity, and to compare these levels with those of men. Methods IGFBP1 levels were determined at baseline and after 8 years in a case–control, prospective study of Swedish women aged 35–56 years. Individuals with normal oral glucose tolerance test (OGTT) who developed abnormal glucose regulation (n=240) were pair matched to controls for age and family history of diabetes and also compared to men of the same age (n=355). Results Low fasting IGFBP1 and increased waist measurement predicted development of diabetes in women (n=60; odds ratio (OR) 70, 95% confidence interval (CI) 8–661, lowest tertile and OR 27, 95% CI 5–141, highest tertile). In women developing diabetes, baseline IGFBP1 levels were lower than expected for fasting insulin values, were associated with impaired suppression after OGTT and increased during 8 years despite an increase in fasting insulin. All individuals in the highest tertile for waist and with ≤40% suppression of IGFBP1 developed diabetes within 8 years. Circulating IGFBP1 concentrations were higher in women compared to men. Women and men who developed diabetes had a similar degree of abdominal obesity, corrected for height. Conclusions We conclude that low IGFBP1 and elevated waist measurement predict diabetes development and that IGFBP1 production is suppressed by a novel factor(s) in women developing diabetes. Increasing levels of IGFBP1 during the emergence of diabetes in men and women suggest the emergence of hepatic insulin resistance. PMID:20508082

  2. 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

  3. 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

  4. 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. PMID:27067614

  5. 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. PMID:26452391

  6. Divergent effects of oxytocin treatment of obese diabetic mice on adiposity and diabetes.

    PubMed

    Altirriba, Jordi; Poher, Anne-Laure; Caillon, Aurélie; Arsenijevic, Denis; Veyrat-Durebex, Christelle; Lyautey, Jacqueline; Dulloo, Abdul; Rohner-Jeanrenaud, Françoise

    2014-11-01

    Oxytocin has been suggested as a novel therapeutic against obesity, because it induces weight loss and improves glucose tolerance in diet-induced obese rodents. A recent clinical pilot study confirmed the oxytocin-induced weight-reducing effect in obese nondiabetic subjects. Nevertheless, the mechanisms involved and the impact on the main comorbidity associated with obesity, type 2 diabetes, are unknown. Lean and ob/ob mice (model of obesity, hyperinsulinemia, and diabetes) were treated for 2 weeks with different doses of oxytocin, analogues with longer half-life (carbetocin) or higher oxytocin receptor specificity ([Thr4,Gly7]-oxytocin). Food and water intake, body weight, and glycemia were measured daily. Glucose, insulin, and pyruvate tolerance, body composition, several hormones, metabolites, gene expression, as well as enzyme activities were determined. Although no effect of oxytocin on the main parameters was observed in lean mice, the treatment dose-dependently reduced food intake and body weight gain in ob/ob animals. Carbetocin behaved similarly to oxytocin, whereas [Thr4,Gly7]-oxytocin (TGOT) and a low oxytocin dose decreased body weight gain without affecting food intake. The body weight gain-reducing effect was limited to the fat mass only, with decreased lipid uptake, lipogenesis, and inflammation, combined with increased futile cycling in abdominal adipose tissue. Surprisingly, oxytocin treatment of ob/ob mice was accompanied by a worsening of basal glycemia and glucose tolerance, likely due to increased corticosterone levels and stimulation of hepatic gluconeogenesis. These results impose careful selection of the conditions in which oxytocin treatment should be beneficial for obesity and its comorbidities, and their relevance for human pathology needs to be determined. PMID:25157455

  7. 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

  8. Circadian phenotyping of obese and diabetic db/db mice.

    PubMed

    Grosbellet, Edith; Dumont, Stephanie; Schuster-Klein, Carole; Guardiola-Lemaitre, Beatrice; Pevet, Paul; Criscuolo, François; Challet, Etienne

    2016-05-01

    Growing evidence links metabolic disorders to circadian alterations. Genetically obese db/db mice, lacking the long isoform of leptin receptor, are a recognized model of type 2 diabetes. In this study, we aimed at characterizing the potential circadian alterations of db/db mice in comparison to db/+ control mice. By using telemetry devices, we first reported arrhythmicity in general activity of most db/db mice under both light-dark cycle and constant darkness, while their rhythm of body temperature is less dramatically disrupted. Water access restricted to nighttime restores significant rhythmicity in behaviorally arrhythmic db/db mice, indicating a masking effect of polydipsia when water is available ad libitum. Endogenous period of temperature rhythm under constant dark conditions is significantly increased (+30 min) in db/db compared with db/+ mice. Next, we studied the oscillations of clock proteins (PER1, PER2 and BMAL1) in the suprachiasmatic nuclei (SCN), the site of the master clock, and detected no difference according to the genotype. Furthermore, c-FOS and P-ERK1/2 expression in response to a light pulse in late night was significantly increased (+80 and +55%, respectively) in the SCN of these diabetic mice. We previously showed that, in addition to altered activity rhythms, db/db mice exhibit altered feeding rhythm. Therefore, we investigated daily patterns of clock protein expression in medial hypothalamic oscillators involved in feeding behavior (arcuate nucleus, ventro- and dorso-medial hypothalamic nuclei). Compared with db/+ mice, very subtle or no difference in oscillations of PER1 and BMAL1 is found in the medial hypothalamus. Although we did not find a clear link between altered hypothalamic clockwork and behavioral rhythms in db/db mice, our results highlight a lengthened endogenous period and altered photic integration in these genetically obese and diabetic mice. PMID:26144489

  9. 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

  10. Diabetes Is an Independent Risk Factor for Severe Nocturnal Hypoxemia in Obese Patients. A Case-Control Study

    PubMed Central

    Lloberes, Patricia; Romero, Odile; Mesa, Jordi; Hernández, Cristina; Simó, Rafael

    2009-01-01

    Background Type 2 diabetes mellitus (T2DM) and obesity have become two of the main threats to public health in the Western world. In addition, obesity is the most important determinant of the sleep apnea-hypopnea syndrome (SAHS), a condition that adversely affects glucose metabolism. However, it is unknown whether patients with diabetes have more severe SAHS than non-diabetic subjects. The aim of this cross-sectional case-control study was to evaluate whether obese patients with T2DM are more prone to severe SAHS than obese non-diabetic subjects. Methodology/Principal Findings Thirty obese T2DM and 60 non-diabetic women closely matched by age, body mass index, waist circumference, and smoking status were recruited from the outpatient Obesity Unit of a university hospital. The exclusion criteria included chronic respiratory disease, smoking habit, neuromuscular and cerebrovascular disease, alcohol abuse, use of sedatives, and pregnancy. Examinations included a non-attended respiratory polygraphy, pulmonary function testing, and an awake arterial gasometry. Oxygen saturation measures included the percentage of time spent at saturations below 90% (CT90). A high prevalence of SAHS was found in both groups (T2DM:80%, nondiabetic:78.3%). No differences in the number of sleep apnea-hypopnea events between diabetic and non-diabetic patients were observed. However, in diabetic patients, a significantly increase in the CT90 was detected (20.2±30.2% vs. 6.8±13,5%; p = 0.027). In addition, residual volume (RV) was significantly higher in T2DM (percentage of predicted: 79.7±18.1 vs. 100.1±22.8; p<0.001). Multiple linear regression analyses showed that T2DM but not RV was independently associated with CT90. Conclusions/Significance T2DM adversely affects breathing during sleep, becoming an independent risk factor for severe nocturnal hypoxemia in obese patients. Given that SAHS is a risk factor of cardiovascular disease, the screening for SAHS in T2DM patients seems

  11. [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

  12. 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

  13. Association Between Maternal Diabetes in Utero and Age at Offspring's Diagnosis of Type 2 Diabetes

    PubMed Central

    Pettitt, David J.; Lawrence, Jean M.; Beyer, Jennifer; Hillier, Teresa A.; Liese, Angela D.; Mayer-Davis, Beth; Loots, Beth; Imperatore, Giuseppina; Liu, Lenna; Dolan, Lawrence M.; Linder, Barbara; Dabelea, Dana

    2008-01-01

    OBJECTIVE—The purpose of this study was to examine age of diabetes diagnosis in youth who have a parent with diabetes by diabetes type and whether the parent's diabetes was diagnosed before or after the youth's birth. RESEARCH DESIGN AND METHODS—The cohort comprised SEARCH for Diabetes in Youth Study participants (diabetes diagnosis 2001–2005) with a diabetic parent. SEARCH is a multicenter survey of youth with diabetes diagnosed before age 20 years. RESULTS—Youth with type 2 diabetes were more likely to have a parent with either type 1 or type 2 diabetes (mother 39.3%; father 21.2%) than youth with type 1 diabetes (5.3 and 6.7%, respectively, P < 0.001 for each). Type 2 diabetes was diagnosed 1.68 years earlier among those exposed to diabetes in utero (n = 174) than among those whose mothers’ diabetes was diagnosed later (P = 0.018, controlled for maternal diagnosis age, paternal diabetes, sex, and race/ethnicity). Age at diagnosis of type 1 diabetes for 269 youth with and without in utero exposure did not differ significantly (difference 0.96 year, P = 0.403 after adjustment). Controlled for the father's age of diagnosis, father's diabetes before the child's birth was not associated with age at diagnosis (P = 0.078 for type 1 diabetes; P = 0.140 for type 2 diabetes). CONCLUSIONS—Type 2 diabetes was diagnosed at younger ages among those exposed to hyperglycemia in utero. Among youth with type 1 diabetes, the effect of the intrauterine exposure was not significant when controlled for mother's age of diagnosis. This study helps explain why other studies have found higher age-specific rates of type 2 diabetes among offspring of women with diabetes. PMID:18694977

  14. 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

  15. 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

  16. 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

  17. Fraction of Gestational Diabetes Mellitus Attributable to Overweight and Obesity by Race/Ethnicity, California, 2007–2009

    PubMed Central

    Kim, Shin Y.; Saraiva, Carina; Curtis, Michael; Wilson, Hoyt G.; Troyan, Jennifer; Sharma, Andrea J.

    2013-01-01

    Objectives. We calculated the racial/ethnic-specific percentages of gestational diabetes mellitus (GDM) attributable to overweight and obesity. Methods. We analyzed 1 228 265 records of women aged 20 years or older with a live, singleton birth in California during 2007 to 2009. Using logistic regression, we estimated the magnitude of the association between prepregnancy body mass index and GDM and calculated the percentages of GDM attributable to overweight and obesity overall and by race/ethnicity. Results. The overall estimated GDM prevalence ranged from 5.4% among White women to 11.9% among Asian/Pacific Islander women. The adjusted percentages of GDM deliveries attributable to overweight and obesity were 17.8% among Asians/Pacific Islander, 41.2% among White, 44.2% among Hispanic, 51.2% among Black, and 57.8% among American Indian women. Select Asian subgroups, such as Vietnamese (13.0%), Asian Indian (14.0%), and Filipino (14.2%), had the highest GDM prevalence, but the lowest percentage attributable to obesity. Conclusions. Elevated prepregnancy body mass index contributed to GDM in all racial/ethnic groups, which suggests that decreasing overweight and obesity among women of reproductive age could reduce GDM, associated delivery complications, and future risk of diabetes in both the mother and offspring. PMID:23947320

  18. Different Roles of Mast Cells in Obesity and Diabetes: Lessons from Experimental Animals and Humans

    PubMed Central

    Shi, Michael A.; Shi, Guo-Ping

    2012-01-01

    Mast cells (MCs) play an important role in allergic hyperresponsiveness and in defending microorganism infections. Recent studies of experimental animals and humans have suggested that MCs participate in obesity and diabetes. MC distribution and activities in adipose tissues may vary, depending on the locations of different adipose tissues. In addition to releasing inflammatory mediators to affect adipose tissue extracellular matrix remodeling and to promote inflammatory cell recruitment and proliferation, MCs directly and indirectly interact and activate adipose tissue cells, including adipocytes and recruited inflammatory cells. Plasma MC protease levels are significantly higher in obese patients than in lean subjects. Experimental obese animals lose body weight after MC inactivation. MC functions in diabetes are even more complicated, and depend on the type of diabetes and on different diabetic complications. Both plasma MC proteases and MC activation essential immunoglobulin E levels are significant risk factors for human pre-diabetes and diabetes mellitus. MC stabilization prevents diet-induced diabetes and improves pre-established diabetes in experimental animals. MC depletion or inactivation can improve diet-induced type 2 diabetes and some forms of type 1 diabetes, but also can worsen other forms of type 1 diabetes, at least in experimental animals. Observations from animal and human studies have suggested beneficial effects of treating diabetic patients with MC stabilizers. Some diabetic patients may benefit from enhancing MC survival and proliferation – hypotheses that merit detailed basic researches and clinical studies. PMID:22566893

  19. 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.

  20. Cardiometabolic Risk Profiles Associated with Chronic Complications in Overweight and Obese Type 2 Diabetes Patients in South China

    PubMed Central

    Chen, Rongping; Yang, Fan; Li, Wei; Chen, Lishu; Lin, Shaoda; Liang, Ganxiong; Chen, Hong

    2014-01-01

    Background Type 2 diabetes is often accompanied by altered cardiometabolic risk profiles, including abdominal obesity, hypertension, and dyslipidaemia. The association of altered cardiometabolic risk profiles with chronic complications of diabetes is not well investigated. Methods We recruited 2954 type 2 diabetes patients with a body mass index ≥25 kg/m2 who visited the diabetes clinics of 62 hospitals in 21 cities in Guangdong province of China from August 2011 to March 2012. Demographic characteristics, personal and family medical histories, and data on chronic complications of diabetes were collected. Clinical examinations and laboratory assessment were conducted. Results Abdominal obesity was found in 91.6% of the study population, elevated blood pressure in 78.3%; elevated serum triacylglycerols in 57.8%, and reduced serum HDL-C in 55.9%. Among the cardiometabolic risk factors, elevated blood pressure was significantly associated with almost all the chronic complications of diabetes. After adjusting for age, gender, duration of diabetes, and HbA1c, elevated blood pressure was significantly associated with diabetic retinopathy (OR 1.63, 95% CI: 1.22–2.19), diabetic nephropathy (OR 3.16, 95% CI: 2.25–4.46), cardiovascular disease (OR 2.71, 95% CI: 1.70–4.32), and stroke (OR 1.90, 95% CI: 1.15–3.12). Abdominal adiposity was significantly associated with diabetic nephropathy (OR 1.39, 95% CI: 1.11–1.74). Elevated triacylglycerols was significantly associated with diabetic retinopathy (OR 1.29, 95% CI: 1.05–1.58) and diabetic nephropathy (OR 1.30, 95% CI: 1.05–1.58). Reduced HDL-C was significantly associated with stroke (OR 1.41, 95% CI: 1.05–1.88). Conclusions Altered cardiometabolic risk profiles, and elevated blood pressure in particular, were significantly associated with chronic complications in overweight and obese patients with type 2 diabetes. Future studies on the prevention of chronic complications of diabetes might make lowering blood

  1. Fat mass and obesity-associated gene rs11642015 polymorphism is significantly associated with prediabetes and type 2 diabetes subsequent to adjustment for body mass index

    PubMed Central

    HAN, LIYUAN; TANG, LINLIN; WANG, CHANGYI; CHEN, ZHONGWEI; ZHANG, TAO; CHEN, SIHAN; LIU, SHENGYUAN; PENG, XIAOLIN; MAI, YIFENG; DUAN, SHIWEI

    2014-01-01

    The association of the fat mass and obesity-associated gene (FTO) rs11642015 polymorphism with prediabetes, type 2 diabetes and obesity in certain populations has not been previously reported. A population-based study was conducted that included 490 type 2 diabetic, 471 prediabetic and 575 normal subjects. The main outcomes of the study were prediabetes, type 2 diabetes and obesity. Binary logistic regression was performed to estimate the association of FTO rs11642015 with the risk of prediabetes, type 2 diabetes and obesity following adjustment for the corresponding confounders. A meta-analysis was also conducted to evaluate the association between FTO rs11642015 and obesity. FTO rs11642015 was significantly associated with prediabetes in the whole sample under the additive model [odds ratio (OR), 1.50; 95% confidence interval (CI), 1.17–1.93; P=0.002], particularly in females. The polymorphism remained consistently significant following adjustment for age and body mass index (BMI), showing an increased prediabetes risk with an additive effect (OR, 1.55; 95% CI, 1.19–2.01; P=0.001). In addition, a significant association was found for rs11642015 with prediabetes and type 2 diabetes under the dominant model. However, under the stringent Bonferroni’s correction there was no evidence of positive associations for FTO rs11642015 with obesity in the whole sample, females or males. Findings of the meta-analysis showed that FTO rs11642015 was not predisposed to obesity. In conclusion, the T allele of FTO rs11642015 is positively associated with an increased risk of prediabetes, even after adjustment for age and BMI, particularly in females. Subjects carrying the CT + TT genotype are predisposed to prediabetes and type 2 diabetes. Therefore, results of the population-based study and follow-up meta-analysis suggested that FTO rs11642015 is not significantly associated with susceptibility to obesity. PMID:25054011

  2. 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

  3. 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

  4. 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

  5. Optimal Waist Circumference Cutoff Value Based on Insulin Resistance and Visceral Obesity in Koreans with Type 2 Diabetes

    PubMed Central

    Lim, Jung Soo; Choi, Young Ju; Kim, Soo-Kyung; Huh, Byoung Wook

    2015-01-01

    Background Visceral obesity is the most powerful contributor to the development of metabolic syndrome (MetS) and cardiovascular diseases. In light of visceral obesity, however, there is a paucity of data on the appropriate cutoff point of waist circumference (WC) in subjects with type 2 diabetes. The aim of this study was to investigate the optimal cutoff value for WC that signals insulin resistance (IR) and visceral obesity in Koreans with type 2 diabetes. Methods We evaluated 4,252 patients with type 2 diabetes (male 2,220, female 2,032, mean age 57.24 years) who visited our clinic between January 2003 and June 2009. WC was measured at the midpoint between the lower rib and the iliac crest, and insulin sensitivity was assessed by the rate constant of plasma glucose disappearance (Kitt %/min) using an insulin tolerance test. Visceral fat thickness was measured using ultrasonography. Statistical analysis was performed using receiver operating characteristic curve. Results The optimal cutoff points for WC for identifying the presence of IR and visceral obesity, as well as two or more metabolic components, were 87 cm for men and 81 cm for women. Moreover, these cutoff points had the highest predictive powers for the presence of visceral obesity. The MetS defined by new criteria correlated with the increased carotid intima-media thickness in female subjects. Conclusion Our results suggest that the optimal cutoff values for WC in Koreans with type 2 diabetes should be reestablished based on IR and visceral obesity. PMID:26124996

  6. Attenuated atrial natriuretic peptide-mediated lipolysis in subcutaneous adipocytes of obese type 2 diabetic men.

    PubMed

    Verboven, Kenneth; Hansen, Dominique; Moro, Cedric; Eijnde, Bert O; Hoebers, Nicole; Knol, Joep; Bouckaert, Wim; Dams, Anne; Blaak, Ellen E; Jocken, Johan W E

    2016-07-01

    Catecholamines and atrial natriuretic peptide (ANP) are major regulators of adipocyte lipolysis. Although obesity is characterized by catecholamine resistance in subcutaneous adipose tissue (SCAT), data on ANP lipolytic response and sensitivity in different adipose tissue (AT) depots of metabolically distinct humans are scarce. Ex vivo catecholamine- and ANP-induced lipolysis was investigated in adipocytes derived from SCAT and visceral AT (VAT) depot of lean (n=13) and obese men, with (n=11) or without (n=18) type 2 diabetes (HbA1c < or ≥ 6.5%). Underlying molecular mechanisms were examined by looking at functional receptors in the NP signalling pathway at the mRNA and protein level. Maximal ANP- and catecholamine-induced lipolysis in SCAT was blunted in obese type 2 diabetics compared with age-matched lean men whereas non-diabetic obese subjects showed intermediate responses. This blunted ANP-mediated lipolytic response was accompanied by lower mRNA and protein expression of the type-A natriuretic peptide (NP) receptor and higher mRNA but reduced protein expression of the scavenging type-C receptor. Maximal ANP-induced lipolysis was lower in VAT compared with SCAT but not different between groups. Collectively, our data show that both ANP- and catecholamine-mediated lipolysis is attenuated in SCAT of obese men with type 2 diabetes, and might be partially explained by NP receptor defects. Therefore, improving maximal ANP responsiveness in adipose tissue might be a potential novel strategy to improve obesity-associated metabolic complications. PMID:27129190

  7. 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

  8. 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

  9. Sarcopenic obesity in aging population: current status and future directions for research.

    PubMed

    Kohara, Katsuhiko

    2014-02-01

    The combination of sarcopenia and obesity, an age-related change in body composition, is a concern in the aged society. Sarcopenic obesity is not the combination of two conditions, but is more related to cardio-metabolic and functional abnormalities. Sarcopenic obesity is associated with more physical functional decline than simple obesity. Sarcopenic obesity may be more insulin resistant, and have a higher risk for metabolic syndrome and atherosclerosis than simple obesity. However, the prevalence of sarcopenic obesity differs substantially among studies because of the lack of a standard definition. For further understanding of the pathophysiological role of sarcopenic obesity, a standardized definition for both sarcopenia and obesity is necessary. PMID:23821364

  10. Hepatocellular Carcinoma in Obesity, Type 2 Diabetes, and NAFLD.

    PubMed

    Reeves, Helen L; Zaki, Marco Y W; Day, Christopher P

    2016-05-01

    Hepatocellular carcinoma (HCC) is the second commonest cause of cancer death worldwide. Rather than falling as a result of prevention and treatments for viral hepatitis, an increase is evident in developed nations consequent to the rising prevalence of obesity and type 2 diabetes mellitus (T2DM)-the two major risk factors for nonalcoholic fatty liver disease (NAFLD). The majority of patients with HCC complicating these conditions present with advanced disease as the tools for surveillance are inadequate, and the "at-risk" population is not well characterized. This review will summarize the epidemiological evidence linking obesity, T2DM, and NAFLD with HCC, what is known about the pathogenic mechanisms involved, as well as their relevance for clinicians managing patients at risk. There will also be an overview of the "unmet needs" surrounding this topic, with suggestions for the direction translational research should take in order to prevent progression of NAFLD to HCC, to improve early detection of HCC in those with NAFLD, as well as to improve outcomes for those affected. PMID:26921078

  11. Type 2 diabetes and obesity: genomics and the clinic.

    PubMed

    Travers, Mary E; McCarthy, Mark I

    2011-07-01

    Type 2 diabetes (T2D) and obesity represent major challenges for global public health. They are at the forefront of international efforts to identify the genetic variation contributing to complex disease susceptibility, and recent years have seen considerable success in identifying common risk-variants. Given the clinical impact of molecular diagnostics in rarer monogenic forms of these diseases, expectations have been high that genetic discoveries will transform the prospects for risk stratification, development of novel therapeutics and personalised medicine. However, so far, clinical translation has been limited. Difficulties in defining the alleles and transcripts mediating association effects have frustrated efforts to gain early biological insights, whilst the fact that variants identified account for only a modest proportion of observed familiarity has limited their value in guiding treatment of individual patients. Ongoing efforts to track causal variants through fine-mapping and to illuminate the biological mechanisms through which they act, as well as sequence-based discovery of lower-frequency alleles (of potentially larger effect), should provide welcome acceleration in the capacity for clinical translation. This review will summarise recent advances in identifying risk alleles for T2D and obesity, and existing contributions to understanding disease pathology. It will consider the progress made in translating genetic knowledge into clinical utility, the challenges remaining, and the realistic potential for further progress. PMID:21647602

  12. 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

  13. 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

  14. 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. PMID:26510873

  15. 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

  16. 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

  17. 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

  18. The Impact of Hypoxemia on Nephropathy in Extremely Obese Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Leong, Wen Bun; Nolen, Melissa; Thomas, G. Neil; Adab, Paymanè; Banerjee, Dev; Taheri, Shahrad

    2014-01-01

    Study Objectives: Diabetes mellitus (DM) is associated with obstructive sleep apnea (OSA) and nephropathy. The hypoxemia associated with OSA may exacerbate renal deterioration in DM nephropathy. We examined the role of hypoxemia in the development of DM nephropathy in severely obese patients. Methods: This cross-sectional study examined anonymized data from 90 DM patients with extreme obesity attending a weight management service. All patients underwent a routine overnight sleep study. Respiratory parameters measured included apnea-hypopnea index (AHI), mean and minimum oxygen (O2) saturations, and time spent under 90% O2 saturation (%TST < 90%). Chronic kidney disease (CKD+) was defined as estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2. Results: Twenty (22%) patients were CKD+. These patients were 7 years older (mean age ± SD 57 ± 11 years, p = 0.003) and had greater adiposity (mean body mass index [BMI] ± SD 50.6 ± 8.7 kg/m2, p = 0.012). No significant differences were found for median AHI and minimum O2 saturation. %TST < 90% was 4 times greater in CKD+ group (p = 0.046). Multivariate regression analysis showed that AHI (β = −0.17, 95% CI: −0.316 to −0.024) and %TST < 90% (β = −0.215, 95% CI: −0.406 to −0.023) were negatively correlated with eGFR after adjustment for age, gender, BMI, comorbidities, insulin treatment, and drugs affecting the renin-angiotensin system. No associations were found between mean and minimum O2 saturations, and eGFR. Conclusion: Apnea and hypopnea events as well as duration of nocturnal hypoxemia were inversely associated with renal function after adjusting for potential confounders. Given the significant burden of renal disease in diabetes, greater vigilance is required in identifying OSA in DM patients with extreme obesity. Citation: Leong WB, Nolen M, Thomas GN, Adab P, Banerjee D, Taheri S. The impact of hypoxemia on nephropathy in extremely obese patients with type 2 diabetes mellitus. J Clin

  19. 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

  20. 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

  1. 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

  2. Metabolic Health Has Greater Impact on Diabetes than Simple Overweight/Obesity in Mexican Americans

    PubMed Central

    Wu, Shenghui; Fisher-Hoch, Susan P.; Reninger, Belinda; Vatcheva, Kristina; McCormick, Joseph B.

    2016-01-01

    Purpose. To compare the risk for diabetes in each of 4 categories of metabolic health and BMI. Methods. Participants were drawn from the Cameron County Hispanic Cohort, a randomly selected Mexican American cohort in Texas on the US-Mexico border. Subjects were divided into 4 phenotypes according to metabolic health and BMI: metabolically healthy normal weight, metabolically healthy overweight/obese, metabolically unhealthy normal weight, and metabolically unhealthy overweight/obese. Metabolic health was defined as having less than 2 metabolic abnormalities. Overweight/obese status was assessed by BMI higher than 25 kg/m2. Diabetes was defined by the 2010 ADA definition or by being on a diabetic medication. Results. The odds ratio for diabetes risk was 2.25 in the metabolically healthy overweight/obese phenotype (95% CI 1.34, 3.79), 3.78 (1.57, 9.09) in the metabolically unhealthy normal weight phenotype, and 5.39 (3.16, 9.20) in metabolically unhealthy overweight/obese phenotype after adjusting for confounding factors compared with the metabolically healthy normal weight phenotype. Conclusions. Metabolic health had a greater effect on the increased risk for diabetes than overweight/obesity. Greater focus on metabolic health might be a more effective target for prevention and control of diabetes than emphasis on weight loss alone. PMID:26881247

  3. 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...

  4. Genetic variants in IRS2 may contribute to obesity and diabetes familial risk in Hispanic children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    IRS2 is a key regulator of glucose homeostasis and an obesity candidate gene, however, its role in children’s susceptibility to obesity and diabetes risk is unknown. Our specific aim was to identify genetic variants explaining a statistically significant quantitative trait locus on chromosome 13q fo...

  5. Associations Between Maternal Pregravid Obesity and Gestational Diabetes and the Timing of Pubarche in Daughters.

    PubMed

    Kubo, Ai; Ferrara, Assiamira; Laurent, Cecile A; Windham, Gayle C; Greenspan, Louise C; Deardorff, Julianna; Hiatt, Robert A; Quesenberry, Charles P; Kushi, Lawrence H

    2016-07-01

    We investigated whether in utero exposure to maternal pregravid obesity and/or gestational diabetes mellitus (GDM) was associated with early puberty in girls. We used data from a longitudinal study of 421 mother-daughter pairs enrolled in an integrated health services organization, Kaiser Permanente Northern California (2005-2012). Girls aged 6-8 years were followed annually through ages 12-14 years. Onset of puberty was assessed using study clinic-based Tanner staging. We examined associations of self-reported pregravid obesity and maternal GDM with timing of the daughter's transition to pubertal maturation stage 2 or above for development of breasts and pubic hair, using accelerated failure time regression models with interval censoring to estimate time ratios and hazard ratios and corresponding 95% confidence intervals. Maternal obesity (pregravid body mass index (BMI; weight (kg)/height (m)(2)) ≥30) was associated with a daughter's earlier transition to breast and pubic hair stage 2+ in comparison with girls whose mothers had pregravid BMI <25. These associations were attenuated and not statistically significant after adjustment for covariates. Girls whose mothers had both pregravid BMI ≥25 and GDM were at higher risk of an earlier transition to pubic hair stage 2+ than those whose mothers had neither condition (adjusted time ratio = 0.89, 95% confidence interval: 0.83, 0.96; hazard ratio = 2.97, 95% confidence interval: 1.52, 5.83). These findings suggest that exposure to maternal obesity and hyperglycemia places girls at higher risk of earlier pubarche. PMID:27268032

  6. 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

  7. 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. PMID:20370939

  8. 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

  9. 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

  10. 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

  11. 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

  12. The role of exercise in reducing the risks of gestational diabetes mellitus in obese women.

    PubMed

    Artal, Raul

    2015-01-01

    The global obesity epidemic continues unabated, now rapidly expanding to developing countries. Multiple comorbidities and premature mortality are associated with obesity, most frequently diabetes. The associated financial and economical burden is escalating as well. The sedentary lifestyle adopted by many pregnant women because of traditional practices and the current recommendation for gestational weight gain are contributing factors to the obesity and diabetes epidemic. Physical inactivity is recognized as an independent risk factor for obesity insulin resistance and type 2 diabetes; the physiological and hormonal changes associated with pregnancy magnify this risk. Conversely, evidence and accumulated experience indicate that antenatal lifestyle interventions that include physical activity and judicious dieting could improve the pregnancy outcome and reduce the risk of gestational diabetes and is effective as an adjunctive therapy for diabetes in pregnancy. All major professional organizations, among them American Congress of Obstetricians and Gynecologists (ACOG), American Diabetes Association (ADA), Royal College of Obstetricians and Gynaecologists (RCOG), and Society of Obstetricians and Gynaecologists of Canada (SOGC), recommend lifestyle interventions that include diet and exercise to prevent or manage gestational diabetes or diabetes mellitus. PMID:25240421

  13. Reducing obesity among employees of a manufacturing plant: translating the Diabetes Prevention Program to the workplace.

    PubMed

    Giese, Karla K; Cook, Paul F

    2014-04-01

    Obesity affects individuals physically and emotionally, contributing to direct and indirect employer costs. Targeted obesity interventions through the Diabetes Prevention Program Lifestyle Core Curriculum offered at the worksite could promote healthy lifestyle decisions resulting in weight improvement among overweight and obese employees. A pretest-posttest cohort design was used to evaluate changes in weight and body mass index among 35 Diabetes Prevention Program participants; they achieved statistically significant changes in body weight (p < .001) and body mass index (p < .001). As a process measure, Diabetes Prevention Program session attendance moderately correlated with weight loss (r = .51; p = .002). Many health care professionals, including occupational health nurses, can implement evidence-based worksite obesity interventions to support employee weight loss. PMID:24702680

  14. 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

  15. 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

  16. 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

  17. Diabetes and cancer: two diseases with obesity as a common risk factor

    PubMed Central

    Garg, S K; Maurer, H; Reed, K; Selagamsetty, R

    2014-01-01

    There is a growing body of evidence to support a connection between diabetes (predominantly type 2), obesity and cancer. Multiple meta-analyses of epidemiological data show that people with diabetes are at increased risk of developing many different types of cancers, along with an increased risk of cancer mortality. Several pathophysiological mechanisms for this relationship have been postulated, including insulin resistance and hyperinsulinaemia, enhanced inflammatory processes, dysregulation of sex hormone production and hyperglycaemia. In addition to these potential mechanisms, a number of common risk factors, including obesity, may be behind the association between diabetes and cancer. Indeed, obesity is associated with an increased risk of cancer and diabetes. Abdominal adiposity has been shown to play a role in creating a systemic pro-inflammatory environment, which could result in the development of both diabetes and cancer. Here, we examine the relationship between diabetes, obesity and cancer, and investigate the potential underlying causes of increased cancer risk in individuals with diabetes. Current treatment recommendations for reducing the overall disease burden are also explored and possible areas for future research are considered. PMID:23668396

  18. Caloric restriction or telmisartan control dyslipidemia and nephropathy in obese diabetic Zücker rats

    PubMed Central

    2014-01-01

    Background The obese Zücker diabetic fatty male rat (ZDF:Gmi™-fa) is an animal model of type II diabetes associated with obesity and related metabolic disturbances like dyslipidaemia and diabetic nephropathy. In addition, diabetic dyslipidaemia has been linked to vascular and glomerular damage too. Dietary fat restriction is a current strategy to tackle obesity and, telmisartan, as a renoprotective agent, may mediate cholesterol efflux by activating PPARγ. To test the hypothesis that both therapeutical alternatives may influence dyslipidaemia and nephropathy in the ZDF rat, we studied their effect on development of diabetes. Methods Male Zücker Diabetic Fatty (ZDF) rats received a low-calorie diet, vehicle or telmisartan for 9 weeks. Blood samples were obtained for analyses of lipids and lipoproteins, LDL-oxidisability, HDL structural and functional properties. Urinalysis was carried out to estimate albumin loss. At the end of the experimental period, rats were sacrificed, liver extracted and APOA1 mRNA quantified. Results Results indicated that low-calorie diet and telmisartan can slower the onset of overt hyperglycaemia and renal damage assessed as albuminuria. Both interventions decreased the oxidative susceptibility of LDL and hepatic APOA1 mRNA expression but only dietary restriction lowered hyperlipidaemia. Conclusion Either a dietary or pharmacologic interventions with telmisartan have important beneficial effects in terms of LDL oxidative susceptibility and progression of albuminuria in obesity related type II diabetes. PMID:24468233

  19. Effects of age and diabetes on scleral stiffness.

    PubMed

    Coudrillier, Baptiste; Pijanka, Jacek; Jefferys, Joan; Sorensen, Thomas; Quigley, Harry A; Boote, Craig; Nguyen, Thao D

    2015-07-01

    The effects of diabetes on the collagen structure and material properties of the sclera are unknown but may be important to elucidate whether diabetes is a risk factor for major ocular diseases such as glaucoma. This study provides a quantitative assessment of the changes in scleral stiffness and collagen fiber alignment associated with diabetes. Posterior scleral shells from five diabetic donors and seven non-diabetic donors were pressurized to 30 mm Hg. Three-dimensional surface displacements were calculated during inflation testing using digital image correlation (DIC). After testing, each specimen was subjected to wide-angle X-ray scattering (WAXS) measurements of its collagen organization. Specimen-specific finite element models of the posterior scleras were generated from the experimentally measured geometry. An inverse finite element analysis was developed to determine the material properties of the specimens, i.e., matrix and fiber stiffness, by matching DIC-measured and finite element predicted displacement fields. Effects of age and diabetes on the degree of fiber alignment, matrix and collagen fiber stiffness, and mechanical anisotropy were estimated using mixed effects models accounting for spatial autocorrelation. Older age was associated with a lower degree of fiber alignment and larger matrix stiffness for both diabetic and non-diabetic scleras. However, the age-related increase in matrix stiffness was 87% larger in diabetic specimens compared to non-diabetic controls and diabetic scleras had a significantly larger matrix stiffness (p = 0.01). Older age was associated with a nearly significant increase in collagen fiber stiffness for diabetic specimens only (p = 0.06), as well as a decrease in mechanical anisotropy for non-diabetic scleras only (p = 0.04). The interaction between age and diabetes was not significant for all outcomes. This study suggests that the age-related increase in scleral stiffness is accelerated in eyes with

  20. Exercise Training suppresses vascular fibrosis in aging obesity induced rats

    PubMed Central

    Kim, Shin Young; Lee, Jin

    2014-01-01

    [Purpose] The aim of this study was to investigate the effects of exercise training (ET) on vascular fibrosis in aging model rats with diet-induced obesity. [Methods] Twenty-four male Sprague-Dawley rats were divided into 3 groups: Aging control (A-C), A-C with high fat diet (AHF), AHF with ET (AHF + ET). Aging was induced by D-galactose (D-gal) and obesity was induced by HFD (60% fat) for 9 weeks. The experimental rats performed swimming (60 min/day, 5 days/week) for 8 weeks. All rat aorta samples were harvested for RT-PCR and morphologic analyses. [Results] The exercise training significantly decreased levels of AT-1, TGF-ß and Coll-1 gene expression compared to AHF group. The AHF + ET group showed a reduced collagen accumulation in the aorta media compared to AHF group. [Conclusion] These results suggest that ET could protect the aging obesity aorta against down-regulation of fibrotic factors (AT-1, TGF-ß and Coll-1 gene) and fibrosis by inhibition of collagen accumulation in the aorta media. PMID:25566453

  1. Studies on the thymus of non-obese diabetic (NOD) mice: effect of transgene expression.

    PubMed Central

    O'Reilly, L A; Healey, D; Simpson, E; Chandler, P; Lund, T; Ritter, M A; Cooke, A

    1994-01-01

    The non-obese diabetic (NOD) mouse is a good model of insulin-dependent diabetes mellitus. Autoreactive T cells may play a fundamental role in disease initiation in this model, while disregulation of such cells may result from an abnormal thymic microenvironment. Diabetes is prevented in NOD mice by direct introduction of an E alpha d transgene (NOD-E) or a modified I-A beta chain of NOD origin (NOD-PRO or NOD-ASP). To investigate if disease pathology in NOD mice, protection from disease in transgenic NOD-E and NOD-PRO and partial protection from disease in NOD-ASP can be attributed to alterations in the thymic microenvironment, immunohistochemical and flow cytometric analysis of the thymi of these mouse strains was studied. Thymi from NOD and NOD-E mice showed a progressive increase in thymic B-cell percentage from 12 weeks of age. This was accompanied by a concomitant loss in thymic epithelial cells with the appearance of large epithelial-free areas mainly at the corticomedullary junction, which increased in size and number with age and contained the B-cell clusters. Such thymic B cells did not express CD5 and were absent in CBA, NOD-ASP and NOD-PRO mice as were the epithelial cell-free spaces, even at 5 months of age. Therefore the mechanisms of disease protection in the transgenic NOD-E and NOD-ASP/NOD-PRO mice may differ if these thymic abnormalities are related to disease. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7523287

  2. The importance of the Non Obese Diabetic (NOD) mouse model in autoimmune diabetes.

    PubMed

    Pearson, James A; Wong, F Susan; Wen, Li

    2016-01-01

    Type 1 Diabetes (T1D) is an autoimmune disease characterized by the pancreatic infiltration of immune cells resulting in T cell-mediated destruction of the insulin-producing beta cells. The successes of the Non-Obese Diabetic (NOD) mouse model have come in multiple forms including identifying key genetic and environmental risk factors e.g. Idd loci and effects of microorganisms including the gut microbiota, respectively, and how they may contribute to disease susceptibility and pathogenesis. Furthermore, the NOD model also provides insights into the roles of the innate immune cells as well as the B cells in contributing to the T cell-mediated disease. Unlike many autoimmune disease models, the NOD mouse develops spontaneous disease and has many similarities to human T1D. Through exploiting these similarities many targets have been identified for immune-intervention strategies. Although many of these immunotherapies did not have a significant impact on human T1D, they have been shown to be effective in the NOD mouse in early stage disease, which is not equivalent to trials in newly-diagnosed patients with diabetes. However, the continued development of humanized NOD mice would enable further clinical developments, bringing T1D research to a new translational level. Therefore, it is the aim of this review to discuss the importance of the NOD model in identifying the roles of the innate immune system and the interaction with the gut microbiota in modifying diabetes susceptibility. In addition, the role of the B cells will also be discussed with new insights gained through B cell depletion experiments and the impact on translational developments. Finally, this review will also discuss the future of the NOD mouse and the development of humanized NOD mice, providing novel insights into human T1D. PMID:26403950

  3. Does albuminuria predict renal risk and/or cardiovascular risk in obese type 2 diabetic patients?

    PubMed

    Bentata, Yassamine; Abouqal, Redouane

    2014-01-01

    Increased urinary albumin excretion (UAE) is a marker of renal and cardiovascular risk in patients with type 2 diabetes (DT2). What about the obese patient with DT2? Does albuminuria predict the progression of renal disease and/or cardiovascular disease? The objective of this study is to determine the link between albuminuria, renal risk and cardiovascular risk in a cohort of obese DT2 patients. This is a prospective study begun in September 2006. It included DT2 patients presenting obesity defined by a body mass index (BMI)>30 Kg/m(2). Three groups of patients were defined: normo-albuminuria (Urinary Albumin Excretion UAE<30 mg/day or Albumin Creatinine Ratio ACR<30 mg/g), micro-albuminuria (UAE=30-300 mg/day or ACR=30-300 mg/g) and macro-albuminuria (UAE>300 mg/day or ACR>300 mg/g). Data on 144 obese DT2 patients were compiled: The mean age of our patients was 59 ± 9 years and the sex ratio 0.26. The incidence of ESRD was higher in the macro-albuminuria group than in the two other groups (26.5% vs. 1.2%, p<0.001). The incidence of cardiovascular events was 15.4%, 14.3% and 23.5% in the normo, micro and macro-albuminuria groups (p=0.48). A history of cardiovascular comorbidities was the main cardiovascular risk in multivariate analysis (0R=15.07; 95% CI=5.30-42.82; p<0.001) and the low admission GFR (0R=5.67; 95% CI=1.23-9.77; p=0.008) was the main factor for progression of kidney disease in multivariate analysis. Albuminuria may be a better marker of kidney disease progression than of cardiovascular risk in the obese DT2 patient, according to our results. However, to accurately demonstrate the link albuminuria - renal risk and albuminuria - cardiovascular risk in the obese DT2 patient, additional studies using very strict criteria of selection and judgment are needed. PMID:24551483

  4. 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

  5. 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

  6. 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

  7. 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

  8. ELECTROCARDIOGRAPHIC ABNORMALITIES AMONG MEXICAN AMERICANS: CORRELATIONS WITH DIABETES, OBESITY, AND THE METABOLIC SYNDROME

    PubMed Central

    Queen, Saulette R.; Smulevitz, Beverly; Rentfro, Anne R.; Vatcheva, Kristina P.; Kim, Hyunggun; McPherson, David D.; Hanis, Craig L.; Fisher-Hoch, Susan P.; McCormick, Joseph B.; Laing, Susan T.

    2012-01-01

    SUMMARY BACKGROUND Resting ischemic electrocardiographic abnormalities have been associated with cardiovascular mortality. Simple markers of abnormal autonomic tone have also been associated with diabetes, obesity, and the metabolic syndrome in some populations. Data on these electrocardiographic abnormalities and correlations with coronary risk factors are lacking among Mexican Americans wherein these conditions are prevalent. OBJECTIVE This study aimed to evaluate the prevalent resting electrocardiographic abnormalities among community-dwelling Mexican Americans, and correlate these findings with coronary risk factors, particularly diabetes, obesity, and the metabolic syndrome. METHODS Study subjects (n=1280) were drawn from the Cameron County Hispanic Cohort comprised of community-dwelling Mexican Americans living in Brownsville, Texas at the United States-Mexico border. Ischemic electrocardiographic abnormalities were defined as presence of ST/T wave abnormalities suggestive of ischemia, abnormal Q waves, and left bundle branch block. Parameters that reflect autonomic tone, such as heart rate-corrected QT interval and resting heart rate, were also measured. RESULTS Ischemic electrocardiographic abnormalities were more prevalent among older persons and those with hypertension, diabetes, obesity, and the metabolic syndrome. Subjects in the highest quartiles of QTc interval and resting heart rate were also more likely to be diabetic, hypertensive, obese, or have the metabolic syndrome. CONCLUSIONS Among Mexican Americans, persons with diabetes, obesity, and the metabolic syndrome were more likely to have ischemic electrocardiographic abnormalities, longer QTc intervals, and higher resting heart rates. A resting electrocardiogram can play a complementary role in the comprehensive evaluation of cardiovascular risk in this minority population. PMID:23515880

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

    PubMed Central

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

    2014-01-01

    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. PMID:19022375

  10. The independent effects of maternal obesity and gestational diabetes on the pregnancy outcomes

    PubMed Central

    2014-01-01

    Background Obesity and gestational diabetes (GDM) in pregnancy are recognized risk factors for adverse outcomes, including cesarean section (CS), macrosomia and preeclampsia. The aim of this study was to investigate the independent effect of GDM and obesity on the adverse pregnancy outcomes at term. Methods A retrospective cohort of postpartum women, in King Khalid University Hospital, were stratified according to body mass index (obese ≥30 kg/m2, non-obese <30 kg/m2) and the results of GDM screening into the following groups, women with no obesity and no GDM (reference group), women with no obesity but with GDM, women with obesity but no GDM and women with both GDM and obesity. Adverse pregnancy outcomes included high birth weight, macrosomia, CS delivery and preeclampsia. Multiple logistic regression used to examine independent associations of GDM and obesity with macrosomia and CS. Results 2701 women were included, 44% of them were obese and 15% had GDM. 63% of the women with GDM were obese. There was significant increase in the percentage of macrosomia, P < 0.001, high birth weight, P < 0.001, CS, P < 0.001 and preeclampsia, P < 0.001 in women with GDM and obesity compared to the reference group. Obesity increased the estimated risk of CS delivery, odds ratio (OR) 2.16, confidence intervals (CI) 1.74-2.67. The combination of GDM and obesity increased the risk of macrosomia OR 3.45, CI 2.05-5.81 and the risk of CS delivery OR 2.26, CI 1.65-3.11. Conclusion Maternal obesity and GDM were independently associated with adverse pregnancy outcomes. The combination of both conditions further increase the risk. PMID:24923207

  11. Association of obesity and treated hypertension and diabetes with cognitive ability in bipolar disorder and schizophrenia

    PubMed Central

    Depp, Colin A; Strassnig, Martin; Mausbach, Brent T; Bowie, Christopher R; Wolyniec, Paula; Thornquist, Mary H; Luke, James R; McGrath, John A; Pulver, Ann E; Patterson, Thomas L; Harvey, Philip D

    2014-01-01

    Objectives People with bipolar disorder or schizophrenia are at greater risk for obesity and other cardio-metabolic risks, and several prior studies have linked these risks to poorer cognitive ability. In a large ethnically homogenous outpatient sample, we examined associations among variables related to obesity, treated hypertension and/or diabetes, and cognitive abilities in these two patient populations. Methods In a study cohort of outpatients with either bipolar disorder (n = 341) or schizophrenia (n = 417), we investigated the association of self-reported body mass index and current use of medications for hypertension or diabetes with performance on a comprehensive neurocognitive battery. We examined sociodemographic and clinical factors as potential covariates. Results Patients with bipolar disorder were less likely to be overweight or obese than patients with schizophrenia, and also less likely to be prescribed medication for hypertension or diabetes. However, obesity and treated hypertension were associated with worse global cognitive ability in bipolar disorder (as well as with poorer performance on individual tests of processing speed, reasoning/problem-solving, and sustained attention), with no such relationships observed in schizophrenia. Obesity was not associated with symptom severity in either group. Conclusions Although less prevalent in bipolar disorder compared to schizophrenia, obesity was associated with substantially worse cognitive performance in bipolar disorder. This association was independent of symptom severity and not present in schizophrenia. Better understanding of the mechanisms and management of obesity may aid in efforts to preserve cognitive health in bipolar disorder. PMID:24725166

  12. 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

  13. Prmt7 Deficiency Causes Reduced Skeletal Muscle Oxidative Metabolism and Age-Related Obesity.

    PubMed

    Jeong, Hyeon-Ju; Lee, Hye-Jin; Vuong, Tuan Anh; Choi, Kyu-Sil; Choi, Dahee; Koo, Sung-Hoi; Cho, Sung Chun; Cho, Hana; Kang, Jong-Sun

    2016-07-01

    Maintenance of skeletal muscle function is critical for metabolic health and the disruption of which exacerbates many chronic diseases such as obesity and diabetes. Skeletal muscle responds to exercise or metabolic demands by a fiber-type switch regulated by signaling-transcription networks that remains to be fully defined. Here, we report that protein arginine methyltransferase 7 (Prmt7) is a key regulator for skeletal muscle oxidative metabolism. Prmt7 is expressed at the highest levels in skeletal muscle and decreased in skeletal muscles with age or obesity. Prmt7(-/-) muscles exhibit decreased oxidative metabolism with decreased expression of genes involved in muscle oxidative metabolism, including PGC-1α. Consistently, Prmt7(-/-) mice exhibited significantly reduced endurance exercise capacities. Furthermore, Prmt7(-/-) mice exhibit decreased energy expenditure, which might contribute to the exacerbated age-related obesity of Prmt7(-/-) mice. Similarly to Prmt7(-/-) muscles, Prmt7 depletion in myoblasts also reduces PGC-1α expression and PGC-1α-promoter driven reporter activities. Prmt7 regulates PGC-1α expression through interaction with and activation of p38 mitogen-activated protein kinase (p38MAPK), which in turn activates ATF2, an upstream transcriptional activator for PGC-1α. Taken together, Prmt7 is a novel regulator for muscle oxidative metabolism via activation of p38MAPK/ATF2/PGC-1α. PMID:27207521

  14. 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

  15. The complexities of obesity, diabetes, and the development and progression of pancreatic cancer

    PubMed Central

    Bao, Bin; Wang, Zhiwei; Li, Yiwei; Kong, Dejuan; Ali, Shadan; Banerjee, Sanjeev; Ahmad, Aamir; Sarkar, Fazlul H.

    2011-01-01

    Pancreatic cancer (PC) is one of the most lethal malignant diseases with the worst prognosis. It is ranked as the fourth leading cause of cancer-related deaths in the United States. Many risk factors have been associated with PC. Interestingly, large numbers of epidemiological studies suggest that obesity and diabetes, especially type-2 diabetes, are positively associated with increased risk of PC. Similarly, these chronic diseases (obesity, diabetes and cancer) are also a major public health concern. In the U.S. population, 50 percent are overweight, 30 percent are medically obese and 10 percent have diabetes mellitus (DM). Therefore, obesity and DM have been considered as potential risk factors for cancers; however, the focus of this article is restricted to PC. Although the mechanisms responsible for the development of these chronic diseases leading to the development of PC are not fully understood, the biological importance of the activation of insulin, insulin like growth factor-1 (IGF-1) and its receptor (IGF-1R) signaling pathways in insulin resistance mechanism and subsequent induction of compensatory hyperinsulinemia has been proposed. Therefore, targeting insulin/IGF-1 signaling with anti-diabetic drugs for lowering blood insulin levels and reversal of insulin-resistance could be useful strategy for the prevention and/or treatment of PC. A large number of studies have demonstrated that the administration of anti-diabetic drugs such as metformin and thiazolidinediones (TZD) class of PPAR-γ agonists decreases the risk of cancers, suggesting that these agents might be useful anti-tumor agents for the treatment of PC. In this review article, we will discuss the potential roles of metformin and TZD anti-diabetic drugs as anti-tumor agents in the context of PC, and will further discuss the complexities and the possible roles of microRNAs (miRNAs) in the pathogenesis of obesity, diabetes and PC. PMID:21129444

  16. The complexities of obesity and diabetes with the development and progression of pancreatic cancer.

    PubMed

    Bao, Bin; Wang, Zhiwei; Li, Yiwei; Kong, Dejuan; Ali, Shadan; Banerjee, Sanjeev; Ahmad, Aamir; Sarkar, Fazlul H

    2011-04-01

    Pancreatic cancer (PC) is one of the most lethal malignant diseases with the worst prognosis. It is ranked as the fourth leading cause of cancer-related deaths in the United States. Many risk factors have been associated with PC. Interestingly, large numbers of epidemiological studies suggest that obesity and diabetes, especially type-2 diabetes, are positively associated with increased risk of PC. Similarly, these chronic diseases (obesity, diabetes, and cancer) are also a major public health concern. In the U.S. population, 50 percent are overweight, 30 percent are medically obese, and 10 percent have diabetes mellitus (DM). Therefore, obesity and DM have been considered as potential risk factors for cancers; however, the focus of this article is restricted to PC. Although the mechanisms responsible for the development of these chronic diseases leading to the development of PC are not fully understood, the biological importance of the activation of insulin, insulin like growth factor-1 (IGF-1) and its receptor (IGF-1R) signaling pathways in insulin resistance mechanism and subsequent induction of compensatory hyperinsulinemia has been proposed. Therefore, targeting insulin/IGF-1 signaling with anti-diabetic drugs for lowering blood insulin levels and reversal of insulin resistance could be useful strategy for the prevention and/or treatment of PC. A large number of studies have demonstrated that the administration of anti-diabetic drugs such as metformin and thiazolidinediones (TZD) class of PPAR-γ agonists decreases the risk of cancers, suggesting that these agents might be useful anti-tumor agents for the treatment of PC. In this review article, we will discuss the potential roles of metformin and TZD anti-diabetic drugs as anti-tumor agents in the context of PC and will further discuss the complexities and the possible roles of microRNAs (miRNAs) in the pathogenesis of obesity, diabetes, and PC. PMID:21129444

  17. 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

  18. 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

  19. 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…

  20. 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

  1. 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

  2. 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

  3. 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

  4. Defective Natriuretic Peptide Receptor Signaling in Skeletal Muscle Links Obesity to Type 2 Diabetes.

    PubMed

    Coué, Marine; Badin, Pierre-Marie; Vila, Isabelle K; Laurens, Claire; Louche, Katie; Marquès, Marie-Adeline; Bourlier, Virginie; Mouisel, Etienne; Tavernier, Geneviève; Rustan, Arild C; Galgani, Jose E; Joanisse, Denis R; Smith, Steven R; Langin, Dominique; Moro, Cedric

    2015-12-01

    Circulating natriuretic peptide (NP) levels are reduced in obesity and predict the risk of type 2 diabetes (T2D). Since skeletal muscle was recently shown as a key target tissue of NP, we aimed to investigate muscle NP receptor (NPR) expression in the context of obesity and T2D. Muscle NPRA correlated positively with whole-body insulin sensitivity in humans and was strikingly downregulated in obese subjects and recovered in response to diet-induced weight loss. In addition, muscle NP clearance receptor (NPRC) increased in individuals with impaired glucose tolerance and T2D. Similar results were found in obese diabetic mice. Although no acute effect of brain NP (BNP) on insulin sensitivity was observed in lean mice, chronic BNP infusion improved blood glucose control and insulin sensitivity in skeletal muscle of obese and diabetic mice. This occurred in parallel with a reduced lipotoxic pressure in skeletal muscle due to an upregulation of lipid oxidative capacity. In addition, chronic NP treatment in human primary myotubes increased lipid oxidation in a PGC1α-dependent manner and reduced palmitate-induced lipotoxicity. Collectively, our data show that activation of NPRA signaling in skeletal muscle is important for the maintenance of long-term insulin sensitivity and has the potential to treat obesity-related metabolic disorders. PMID:26253614

  5. Identification of diabetes- and obesity-associated proteomic changes in human spermatozoa by difference gel electrophoresis.

    PubMed

    Kriegel, Thomas M; Heidenreich, Falk; Kettner, Karina; Pursche, Theresia; Hoflack, Bernard; Grunewald, Sonja; Poenicke, Kerstin; Glander, Hans-Juergen; Paasch, Uwe

    2009-11-01

    Difference gel electrophoresis (DIGE) of fluorescently labelled human sperm proteins was used to identify diabetes- and obesity-associated changes of the sperm proteome. Semen samples from type 1 diabetics, non-diabetic obese individuals and a reference group of clinically healthy fertile donors were evaluated in a comparative study. The adaptation of a general protein extraction procedure to the solubilization of proteins from isolated progressively motile human spermatozoa resulted in the detection of approximately 2700 fluorescent protein spots in the DIGE images. Comparison of the patients' sperm proteomes with those of the reference group allowed the identification of 20 spots containing proteins that were present in the sperm lysates at significantly increased or decreased concentrations. In detail, eight of these spots were apparently related to type 1 diabetes while 12 spots were apparently related to obesity. Tryptic digestion of the spot proteins and mass spectrometric analysis of the corresponding peptides identified seven sperm proteins apparently associated with type 1 diabetes and nine sperm proteins apparently associated with obesity, three of which existing in multiple molecular forms. The established proteomic approach is expected to function as a non-invasive experimental tool in the diagnosis of male infertility and in monitoring any fertility-restoring therapy. PMID:20021714

  6. Alternanthera sessilis Red Ethyl Acetate Fraction Exhibits Antidiabetic Potential on Obese Type 2 Diabetic Rats

    PubMed Central

    Tan, Kok Keong; Kim, Kah Hwi

    2013-01-01

    The antidiabetic potential of Alternanthera sessilis Red was investigated using the obese type 2 diabetic rats induced by high fat diet and streptozotocin. Three fractions (hexane, ethyl acetate, and water) were obtained from the crude ethanol extract of Alternanthera sessilis Red. Alternanthera sessilis Red ethyl acetate fraction (ASEAF) was found to possess the most potent antihyperglycemic effect through oral glucose tolerance test. The ASEAF was subsequently given to the diabetic rats for two weeks. It was found that two-week administration of ASEAF reduces the fasting blood glucose level, triglyceride level, and free fatty acid level of the rats. ASEAF-treated diabetic rats showed higher pancreatic insulin content and pancreatic total superoxide dismutase activity compared to the untreated diabetic rats. Also, the insulin sensitivity indexes suggested that ASEAF ameliorates the insulin resistant state of the diabetic rats. In conclusion, ASEAF could be developed into a potential antidiabetic agent for the management of type 2 diabetes. PMID:23606892

  7. 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

  8. Rapamycin Normalizes Serum Leptin by Alleviating Obesity and Reducing Leptin Synthesis in Aged Rats.

    PubMed

    Scarpace, Philip J; Matheny, Michael; Strehler, Kevin Y E; Toklu, Hale Zerrin; Kirichenko, Nataliya; Carter, Christy S; Morgan, Drake; Tümer, Nihal

    2016-07-01

    This investigation examines whether a low intermittent dose of rapamycin will avoid the hyperlipidemia and diabetes-like syndrome associated with rapamycin while still decreasing body weight and adiposity in aged obese rats. Furthermore, we examined if the rapamycin-mediated decrease in serum leptin was a reflection of decreased adiposity, diminished leptin synthesis, or both. To these ends, rapamycin (1mg/kg) was administered three times a week to 3 and 24-month old rats. Body weight, food intake, body composition, mTORC1 signaling, markers of metabolism, as well as serum leptin levels and leptin synthesis in adipose tissue were examined and compared to that following a central infusion of rapamycin. Our data suggest that the dosing schedule of rapamycin acts on peripheral targets to inhibit mTORC1 signaling, preferentially reducing adiposity and sparing lean mass in an aged model of obesity resulting in favorable outcomes on blood triglycerides, increasing lean/fat ratio, and normalizing elevated serum leptin with age. The initial mechanism underlying the rapamycin responses appears to have a peripheral action and not central. The peripheral rapamycin responses may communicate an excessive nutrients signal to the hypothalamus that triggers an anorexic response to reduce food consumption. This coupled with potential peripheral mechanism serves to decrease adiposity and synthesis of leptin. PMID:25617379

  9. Exercise training starting at weaning age preserves cardiac pacemaker function in adulthood of diet-induced obese rats.

    PubMed

    Carvalho de Lima, Daniel; Guimarães, Juliana Bohnen; Rodovalho, Gisele Vieira; Silveira, Simonton Andrade; Haibara, Andrea Siqueira; Coimbra, Cândido Celso

    2014-08-01

    Peripheral sympathetic overdrive in young obese subjects contributes to further aggravation of insulin resistance, diabetes, and hypertension, thus inducing worsening clinical conditions in adulthood. Exercise training has been considered a strategy to repair obesity autonomic dysfunction, thereby reducing the cardiometabolic risk. Therefore, the aim of this study was to assess the effect of early exercise training, starting immediately after weaning, on cardiac autonomic control in diet-induced obese rats. Male Wistar rats (weaning) were divided into four groups: (i) a control group (n = 6); (ii) an exercise-trained control group (n = 6); (iii) a diet-induced obesity group (n = 6); and (iv) an exercise-trained diet-induced obesity group (n = 6). The development of obesity was induced by 9 weeks of palatable diet intake, and the training program was implemented in a motor-driven treadmill (5 times per week) during the same period. After this period, animals were submitted to vein and artery catheter implantation to assess cardiac autonomic balance by methylatropine (3 mg/kg) and propranolol (4 mg/kg) administration. Exercise training increased running performance in both groups (p < 0.05). Exercise training also prevented the increased resting heart rate in obese rats, which seemed to be related to cardiac pacemaker activity preservation (p < 0.05). Additionally, the training program preserved the pressure and bradycardia responses to autonomic blockade in obese rats (p < 0.05). An exercise program beginning at weaning age prevents cardiovascular dysfunction in obese rats, indicating that exercise training may be used as a nonpharmacological therapeutic strategy for the treatment of cardiometabolic diseases. PMID:24806307

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

    PubMed

    Nakajima, Kei

    2016-03-25

    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

  11. 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

  12. Improvement in binge eating in non-diabetic obese individuals after 3 months of treatment with liraglutide - A pilot study.

    PubMed

    Robert, Sarah Anne; Rohana, Abdul Ghani; Shah, Shamsul Azhar; Chinna, Karuthan; Wan Mohamud, Wan Nazaimoon; Kamaruddin, Nor Azmi

    2015-01-01

    We examined the effects of liraglutide, a glucagon-like peptide-1 analogue on appetite and plasma ghrelin in non-diabetic obese participants with subclinical binge eating (BE). Forty-four obese BE participants (mean age: 34±9 years, BMI: 35.9±4.2kg/m(2)) were randomly assigned to intervention or control groups for 12 weeks. All participants received standard advice for diet and exercise. Binge eating score, ghrelin levels and other anthropometric variables were evaluated at baseline and at the end of the study. Participants who received liraglutide showed significant improvement in binge eating, accompanied by reduction in body weight, BMI, waist circumference, systolic blood pressure, fasting glucose and total cholesterol. Ghrelin levels were significantly increased which may potentially diminish the weight loss effects of liraglutide beyond the intervention. PMID:25870084

  13. Aging exacerbates obesity-induced cerebromicrovascular rarefaction, neurovascular uncoupling, and cognitive decline in mice.

    PubMed

    Tucsek, Zsuzsanna; Toth, Peter; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Warrington, Junie P; Giles, Cory B; Wren, Jonathan D; Koller, Akos; Ballabh, Praveen; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2014-11-01

    Epidemiological studies show that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular impairment, we compared young (7 months) and aged (24 months) high-fat diet-fed obese C57BL/6 mice. We found that aging exacerbates the obesity-induced decline in microvascular density both in the hippocampus and in the cortex. The extent of hippocampal microvascular rarefaction and the extent of impairment of hippocampal-dependent cognitive function positively correlate. Aging exacerbates obesity-induced loss of pericyte coverage on cerebral microvessels and alters hippocampal angiogenic gene expression signature, which likely contributes to microvascular rarefaction. Aging also exacerbates obesity-induced oxidative stress and induction of NADPH oxidase and impairs cerebral blood flow responses to whisker stimulation. Collectively, obesity exerts deleterious cerebrovascular effects in aged mice, promoting cerebromicrovascular rarefaction and neurovascular uncoupling. The morphological and functional impairment of the cerebral microvasculature in association with increased blood-brain barrier disruption and neuroinflammation (Tucsek Z, Toth P, Sosnowsk D, et al. Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer's disease. J Gerontol Biol Med Sci. 2013. In press, PMID: 24269929) likely contribute to obesity-induced cognitive decline in aging. PMID:24895269

  14. 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. PMID:1882180

  15. 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

  16. Diabetes and obesity risks in African American young adult freshmen attending a historically black college/university.

    PubMed

    Owens, Chequita Smith

    2008-11-01

    Convincing African American and other young adults that obesity increases their risk for diabetes and its complications is challenging for health educators and clinicians. At a historically Black university (HBCU) this question was examined, Do overweight and obese African American freshmen have higher risks for diabetes through low physical activity or toning and poor nutritional habits? Survey data found 40% of the 101 respondents sampled there were obese (defined as body mass index of 30 or more kg/m2), which is a higher proportion of obesity than found in other college health surveys. Scores reflecting higher risks of diabetes mellitus were significantly related to higher BMI values and low aerobic physical activity. Students had low levels of physical activity and toning than reported in general college populations. To reduce diabetes-disparity risks and obesity-related behaviors, African American younger adult freshmen may benefit from effective intervention strategies targeting them. PMID:19029739

  17. 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…

  18. Metabolomics - the complementary field in systems biology: a review on obesity and type 2 diabetes.

    PubMed

    Abu Bakar, Mohamad Hafizi; Sarmidi, Mohamad Roji; Cheng, Kian-Kai; Ali Khan, Abid; Suan, Chua Lee; Zaman Huri, Hasniza; Yaakob, Harisun

    2015-07-01

    Metabolomic studies on obesity and type 2 diabetes mellitus have led to a number of mechanistic insights into biomarker discovery and comprehension of disease progression at metabolic levels. This article reviews a series of metabolomic studies carried out in previous and recent years on obesity and type 2 diabetes, which have shown potential metabolic biomarkers for further evaluation of the diseases. Literature including journals and books from Web of Science, Pubmed and related databases reporting on the metabolomics in these particular disorders are reviewed. We herein discuss the potential of reported metabolic biomarkers for a novel understanding of disease processes. These biomarkers include fatty acids, TCA cycle intermediates, carbohydrates, amino acids, choline and bile acids. The biological activities and aetiological pathways of metabolites of interest in driving these intricate processes are explained. The data from various publications supported metabolomics as an effective strategy in the identification of novel biomarkers for obesity and type 2 diabetes. Accelerating interest in the perspective of metabolomics to complement other fields in systems biology towards the in-depth understanding of the molecular mechanisms underlying the diseases is also well appreciated. In conclusion, metabolomics can be used as one of the alternative approaches in biomarker discovery and the novel understanding of pathophysiological mechanisms in obesity and type 2 diabetes. It can be foreseen that there will be an increasing research interest to combine metabolomics with other omics platforms towards the establishment of detailed mechanistic evidence associated with the disease processes. PMID:25919044

  19. [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

  20. 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 ...

  1. 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...

  2. Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling

    PubMed Central

    Yadav, Hariom; Quijano, Celia; Kamaraju, Anil K.; Gavrilova, Oksana; Malek, Rana; Chen, Weiping; Zerfas, Patricia; Zhigang, Duan; Wright, Elizabeth C.; Stuelten, Christina; Sun, Peter; Lonning, Scott; Skarulis, Monica; Sumner, Anne E.; Finkel, Toren; Rane, Sushil G.

    2011-01-01

    SUMMARY Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an important role of the TGF-β/Smad3 signaling pathway in regulating glucose and energy homeostasis. Smad3 deficient mice are protected from diet-induced obesity and diabetes. Interestingly, the metabolic protection is accompanied by Smad3−/− white adipose tissue acquiring the bioenergetic and gene expression profile of brown fat/skeletal muscle. Smad3−/− adipocytes demonstrate a marked increase in mitochondrial biogenesis, with a corresponding increase in basal respiration, and Smad3 acts as a repressor of PGC-1α expression. We observe significant correlation between TGF-β1 levels and adiposity in rodents and humans. Further, systemic blockade of TGF-β1 signaling protects mice from obesity, diabetes and hepatic steatosis. Together, these results demonstrate that TGF-β signaling regulates glucose tolerance and energy homeostasis and suggest that modulation of TGF-β1 activity might be an effective treatment strategy for obesity and diabetes. PMID:21723505

  3. 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...

  4. 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

  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. 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.

  7. The association between obesity and acute myocardial infarction is age- and gender-dependent in a Japanese population.

    PubMed

    Oda, Eiji; Goto, Masayuki; Matsushita, Hirooki; Takarada, Ken; Tomita, Makoto; Saito, Atsushi; Fuse, Koichi; Fujita, Satoru; Ikeda, Yoshio; Kitazawa, Hitoshi; Takahashi, Minoru; Sato, Masahito; Okabe, Masaaki; Aizawa, Yoshifusa

    2013-09-01

    Controversies concerning the association between obesity and acute myocardial infarction (AMI) are still ongoing in Japan. We investigated the association between obesity defined by body mass index of 25 kg/m(2) or higher and AMI by a case-control study using data from 1199 AMI cases and 4056 apparently healthy controls. The analysis was performed in age- and sex-matched samples of 621 case-control pairs younger than 80 years and in crude samples aged 40-79 years divided into 10-year age groups. Prevalence of obesity, diabetes, current smoking, hypertension, and hypercholesterolemia were compared between cases and controls, and a multivariable odds ratio (OR) of AMI was calculated for each risk factor in various age groups. The OR (95 % confidence interval (CI)) of AMI for obesity was 1.63 (1.23-2.17), P = 0.0008 in men younger than 80 years; 2.65 (1.41-5.00), P = 0.0025 in women younger than 80 years; 2.23 (1.46-3.41), P = 0.0002 in men aged 59 years or younger; 1.34 (0.90-2.01), P = 0.1510 in men aged 60-79 years; and 2.98 (1.56-5.71), P = 0.0010 in women aged 60-79 years using paired samples. The OR (95 % CI) of AMI for obesity was 4.92 (2.53-9.58), P < 0.0001 in men aged 40-49 years; 1.54 (1.07-2.21), P = 0.0197 in men aged 50-59 years; 1.07 (0.69-1.66), P = 0.7717 in men aged 60-69 years; 2.24 (1.20-4.20), P = 0.0118 in men aged 70-79 years; 2.48 (1.12-5.48), P = 0.0245 in women aged 60-69 years; and 3.05 (1.46-6.37), P = 0.0029 in women aged 70-79 years using crude samples. The association between obesity and AMI was age- and gender-dependent in a Japanese population. PMID:22975714

  8. Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus.

    PubMed

    Moberly, Steven P; Mather, Kieren J; Berwick, Zachary C; Owen, Meredith K; Goodwill, Adam G; Casalini, Eli D; Hutchins, Gary D; Green, Mark A; Ng, Yen; Considine, Robert V; Perry, Kevin M; Chisholm, Robin L; Tune, Johnathan D

    2013-07-01

    Glucagon-like peptide 1 (GLP-1) has insulin-like effects on myocardial glucose uptake which may contribute to its beneficial effects in the setting of myocardial ischemia. Whether these effects are different in the setting of obesity or type 2 diabetes (T2DM) requires investigation. We examined the cardiometabolic actions of GLP-1 (7-36) in lean and obese/T2DM humans, and in lean and obese Ossabaw swine. GLP-1 significantly augmented myocardial glucose uptake under resting conditions in lean humans, but this effect was impaired in T2DM. This observation was confirmed and extended in swine, where GLP-1 effects to augment myocardial glucose uptake during exercise were seen in lean but not in obese swine. GLP-1 did not increase myocardial oxygen consumption or blood flow in humans or in swine. Impaired myocardial responsiveness to GLP-1 in obesity was not associated with any apparent alterations in myocardial or coronary GLP1-R expression. No evidence for GLP-1-mediated activation of cAMP/PKA or AMPK signaling in lean or obese hearts was observed. GLP-1 treatment augmented p38-MAPK activity in lean, but not obese cardiac tissue. Taken together, these data provide novel evidence indicating that the cardiometabolic effects of GLP-1 are attenuated in obesity and T2DM, via mechanisms that may involve impaired p38-MAPK signaling. PMID:23764734

  9. 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

  10. 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

  11. 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…

  12. 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...

  13. 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…

  14. 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

  15. [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

  16. 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

  17. 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

  18. Effect of Pleurotus tuber-regium polysaccharides supplementation on the progression of diabetes complications in obese-diabetic rats.

    PubMed

    Huang, Hui-Yu; Korivi, Mallikarjuna; Yang, Hui-Ting; Huang, Chi-Chang; Chaing, Ying-Ying; Tsai, Ying-Chieh

    2014-08-31

    In this study, the effect of mushroom extracellular polysaccharides on fatty acid composition and liver peroxisome proliferator-activated receptor-alpha (PPAR-α) expression in obese-diabetic rats was investigated, and distinguished the association among anti-obesity, hypoglycemic and hypolipidemic properties. Extracellular polysaccharides from three different strains of Pleurotus tuber-regium were extracted and labeled as HP (high-percentage), MP (medium-percentage) and LP (low-percentage). Obese- diabetes (OD) was induced by chronic high-fat diet plus streptozotocin (STZ) injections. Simultaneously to the diet, polysaccharides were orally administered to OD groups (20 mg/kg body weight/8-week), and categorized into OD+HP, OD+MP and OD+LP groups (n = 10/group), respectively. High-fat diet plus STZ-induced hyperglycemia was prominently attenuated by polysaccharides. Increased fatty acid component n-6/n-3 ratio in liver and plasma of obese-diabetic rats was attenuated, while, reduced MUFA/ PUFA and MUFA/SFA ratios were restored (P < 0.01) with polysaccharides treatment. Furthermore, elevated serum total cholesterol, triglycerides and low-density lipoprotein (LDL) concentrations were controlled, and parallel restoration of decreased high-density lipoprotein (HDL) levels were found with polysaccharides supplementation. This hypolipidemic property might be associated with up-regulated liver PPAR-α mRNA expression and protein levels (P < 0.01). These findings concluded that stable fatty acid components and activated PPAR-α by polysaccharides may contribute to its hypoglycemic and hypolipidemic properties. Therefore, P. tuber-regium could be considered as nutritional supplement to treat diabetic complications. PMID:25246061

  19. In utero exposure to maternal obesity and diabetes: animal models that identify and characterize implications for future health.

    PubMed

    Nathanielsz, Peter W; Poston, Lucilla; Taylor, Paul D

    2007-06-01

    The developed and developing worlds are experiencing an epidemic of obesity and associated predisposition to diabetes. This epidemic places a major drain on health care resources. It is now clear that maternal obesity and gestational diabetes have major adverse effects on the developing fetus that lead to increased neonatal morbidity and mortality, as discussed elsewhere in this issue. Obesity in pregnancy and gestational diabetes represent a special problem, not only as a result of their immediate adverse effects on maternal health and pregnancy outcome, but also because of growing evidence for their persistent and deleterious effects on the developing child. PMID:17572267

  20. In utero exposure to maternal obesity and diabetes: animal models that identify and characterize implications for future health.

    PubMed

    Nathanielsz, Peter W; Poston, Lucilla; Taylor, Paul D

    2007-12-01

    The developed and developing worlds are experiencing an epidemic of obesity and associated predisposition to diabetes. This epidemic places a major drain on health care resources. It is now clear that maternal obesity and gestational diabetes have major adverse effects on the developing fetus that lead to increased neonatal morbidity and mortality, as discussed elsewhere in this issue. Obesity in pregnancy and gestational diabetes represent a special problem, not only as a result of their immediate adverse effects on maternal health and pregnancy outcome, but also because of growing evidence for their persistent and deleterious effects on the developing child. PMID:18063102

  1. 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

  2. A systematic review of Gymnema sylvestre in obesity and diabetes management.

    PubMed

    Pothuraju, Ramesh; Sharma, Raj Kumar; Chagalamarri, Jayasimha; Jangra, Surender; Kumar Kavadi, Praveen

    2014-03-30

    The prevalence of obesity is associated with many health-related problems. Currently, more than 300 million people are considered to be obese. According to the World Health Organization (WHO), by 2030, 87 and 439 million people will be affected in India and the world, respectively. Today, herbal medicines are gaining interest in the treatment of obesity and diabetes, because of their minimal side effects. Gymnemic acid - an active component isolated from Gymnema sylvestre - has anti-obesity and antidiabetic properties, decreases body weight and also inhibits glucose absorption. Several components extracted from Gymnema prevent the accumulation of triglycerides in muscle and liver, and also decrease fatty acid accumulation in the circulation. In this paper, an attempt has been made to review the effects of various extracts from Gymnema sylvestre in the regulation of carbohydrate and lipid metabolism in both animal and clinical studies. PMID:24166097

  3. Evidence for independent genetic influences on obesity in middle age.

    PubMed

    Fabsitz, R R; Carmelli, D; Hewitt, J K

    1992-09-01

    The National Heart, Lung, and Blood Institute (NHLBI) Twin Study provided longitudinal data on a cohort of 514 pairs of adult male twin pairs who were examined at approximate ages of 48, 57, and 63 years. Because the sample was selected from military veterans, height and weight data were also available from their induction physical examinations when they were approximately 20 years of age. From the total NHLBI Twin Study cohort, 124 monozygotic and 119 dizygotic male twin pairs had complete data available for both members of the pair at induction and three examinations spanning 43 years of adult life. Using these data, the contributions of genetics and shared and non-shared environmental factors to BMI over the 43 year period were estimated by model fitting procedures. Model fitting included both a factor decomposition of these effects as well as a developmental path model. Results from the decomposition procedure indicate significant genetic effects at each examination cycle. Fitting a developmental path model, two independent genetic contributions to the variability of BMI were found: one at, or prior to, the induction examination about age 20, and a second between ages 20 and 48. Significant non-shared environmental contributions at each examination were also indicated, but shared environmental effects were not significant. We conclude that cumulative genetic effects explain most of the tracking in obesity over time; non-shared environmental effects, although significant at each age, are relatively short-lived and make only a minor contribution to tracking. PMID:1328090

  4. The diabetes and obesity epidemic among the Pima Indians.

    PubMed

    Krosnick, A

    2000-08-01

    The Pima Indians are the fattest population group in the fattest country on earth, and they have the highest prevalence of diabetes in the world. Despite unprecedented research by the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases (NIH) and good care by the Indian Health Service (IHS), the problems have grown worse since first recognized in 1963. The causes are multiple: environmental, genetic, cultural, and psychosocial. The real villian, however, is the disease, diabetes. The solution is prevention in Pima children. PMID:10959174

  5. 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

  6. Obesity.

    PubMed

    Callaway, C W

    1987-01-01

    Obesity is not a single disease, but a variety of conditions resulting from different mechanisms and associated with various types and degrees of risks. To determine who should lose weight, how much weight should be lost, and how to undertake weight loss, the following types of information are needed: personal-demographic data, developmental patterns, family history, energy balance, body composition/fat distribution, psychological/behavioral measures, endocrine/metabolic measures, complications and associated conditions. Weight reduction should be undertaken by women with morbid obesity, with complications secondary to the obesity, with a strong family history of conditions associated with obesity, or with increased abdomen:hip ratios. In contrast, women who have excess weight localized in the hips and thighs and no personal or family history of associated conditions may not benefit from dietary restriction. Low calorie diets result in adaptive changes, "designed" to prolong survival in the face of famine. These include changes in water balance, metabolic rate, and appetite. Metabolic rate declines, allowing the individual to burn fewer and fewer calories. Each time a woman diets she tends to lose weight less rapidly than the time before. "Restrained eating" predisposes binge eating. Indeed, bulimia rarely occurs in the absence of prior caloric restrictions. Current medical definitions of obesity do not consider these nuances. Existing definitions "over-diagnose" obesity in women, in general, and in older women and nonwhite women, in particular. For example, by existing standards, more than 60 percent of black women more than 45 years of age are considered obese. In contrast, the health risks of similar degrees of obesity are substantially greater for men than for women. Part of the problems lies in the fact that many women have pear-shaped fat distribution,a pattern which is not associated with increased health risks.Current cultural definitions of obesity for

  7. Systems genetics of susceptibility to obesity-induced diabetes in mice

    PubMed Central

    van Nas, Atila; Castellani, Lawrence W.; Zhao, Yi; Zhou, Zhiqiang; Wen, Pingzi; Yu, Suzanne; Qi, Hongxiu; Rosales, Melenie; Schadt, Eric E.; Broman, Karl W.; Péterfy, Miklós; Lusis, Aldons J.

    2012-01-01

    Inbred strains of mice are strikingly different in susceptibility to obesity-driven diabetes. For instance, deficiency in leptin receptor (db/db) leads to hyperphagia and obesity in both C57BL/6 and DBA/2 mice, but only on the DBA/2 background do the mice develop beta-cell loss leading to severe diabetes, while C57BL/6 mice are relatively resistant. To further investigate the genetic factors predisposing to diabetes, we have studied leptin receptor-deficient offspring of an F2 cross between C57BL/6J (db/+) males and DBA/2J females. The results show that the genetics of diabetes susceptibility are enormously complex and a number of quantitative trait loci (QTL) contributing to diabetes-related traits were identified, notably on chromosomes 4, 6, 7, 9, 10, 11, 12, and 19. The Chr. 4 locus is likely due to a disruption of the Zfp69 gene in C57BL/6J mice. To identify candidate genes and to model coexpression networks, we performed global expression array analysis in livers of the F2 mice. Expression QTL (eQTL) were identified and used to prioritize candidate genes at clinical trait QTL. In several cases, clusters of eQTLs colocalized with clinical trait QTLs, suggesting a common genetic basis. We constructed coexpression networks for both 5 and 12 wk old mice and identified several modules significantly associated with clinical traits. One module in 12 wk old mice was associated with several measures of hepatic fat content as well as with other lipid- and diabetes-related traits. These results add to the understanding of the complex genetic interactions contributing to obesity-induced diabetes. PMID:22010005

  8. Pharmacotherapy considerations in diabetes and obesity: setting patients up for success.

    PubMed

    Cornell, Susan; D'Souza, Jennifer

    2014-03-01

    The causal relationship between obesity and type 2 diabetes mellitus has been acknowledged over the past few decades and is frequently expressed by the term diabesity. It is predicted that the number of people with diabetes mellitus (DM) and prediabetes will continue to rise, with obesity placing people at increased risk for diabetic complications and comorbidities. Therefore, an individualized, patient-centered care approach is needed to optimally treat and manage the obese patient with DM. With 11 classes of medications available to lower blood glucose levels, 2 new agents for weight loss, and various surgical procedures, the clinician and the patient have numerous options from which to choose. In an effort to promote optimal disease management, clinicians should work with their obese patients to select appropriate pharmacotherapy combinations that will enable the patients to successfully manage DM. The current clinical recommendations and guidelines emphasize the need to consider the weight effects of the various DM agents as monotherapy and in combination. Additionally, with the approval of 2 new weight loss medications, the clinician must be aware of the place of the medications in therapy and their appropriate use in combination with DM pharmacotherapy. PMID:24685973

  9. Hippocampal calcium dysregulation at the nexus of diabetes and brain aging

    PubMed Central

    Thibault, Olivier; Anderson, Katie L.; DeMoll, Chris; Brewer, Lawrence D.; Landfield, Philip W.; Porter, Nada M.

    2013-01-01

    Accumulating evidence is associating disorders of lipid and glucose metabolism, including the overlapping conditions of insulin resistance/metabolic syndrome, obesity and diabetes, with moderate cognitive impairment in normal aging and elevated risk of Alzheimer’s disease. It appears that a common feature of these conditions is deficient insulin signaling, likely affecting the brain as well as canonical peripheral target tissues. A number of studies have documented that insulin directly affects brain processes and that reduced insulin signaling results in impaired learning and memory. Several studies have also shown that deficient insulin signaling induces Ca2+ dysregulation in neurons. Because brain aging is associated with substantial Ca2+ dyshomeostasis, it has been proposed that deficient insulin signaling exacerbates or accelerates aging-related Ca2+ dyshomeostasis. However, there have been few studies examining insulin interactions with Ca2+ regulation in aging animals. We have been testing predictions of the Ca2+ dysregulation/diabetes/brain aging hypothesis and have found that insulin and insulin sensitizers (thiazolidinediones) target several hippocampal Ca2+-related processes affected by aging, including larger Ca2+ transients and Ca2+-dependent afterhyperpolarizations, and counteract the effects of aging on those processes. Thus, while additional testing is needed, the results to date are consistent with the view that effects of deficient insulin signaling on brain aging are mediated in part by neuronal Ca2+ dyshomeostasis. PMID:23872402

  10. 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

  11. 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

  12. Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity.

    PubMed

    Derbenev, Andrei V; Zsombok, Andrea

    2016-05-01

    Diabetes mellitus and obesity, which is a major risk factor in the development of type 2 diabetes mellitus, have reached epidemic proportions worldwide including the USA. The current statistics and forecasts, both short- and long-term, are alarming and predict severe problems in the near future. Therefore, there is a race for developing new compounds, discovering new receptors, or finding alternative solutions to prevent and/or treat the symptoms and complications related to obesity and diabetes mellitus. It is well demonstrated that members of the transient receptor potential (TRP) superfamily play a crucial role in a variety of biological functions both in health and disease. In the recent years, transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) were shown to have beneficial effects on whole body metabolism including glucose homeostasis. TRPV1 and TRPA1 have been associated with control of weight, pancreatic function, hormone secretion, thermogenesis, and neuronal function, which suggest a potential therapeutic value of these channels. This review summarizes recent findings regarding TRPV1 and TRPA1 in association with whole body metabolism with emphasis on obese and diabetic conditions. PMID:26403087

  13. Aerobic exercise in obese diabetic patients with chronic kidney disease: a randomized and controlled pilot study

    PubMed Central

    2009-01-01

    Background Patients with obesity, diabetes, and chronic kidney disease (CKD) are generally physically inactive, have a high mortality rate, and may benefit from an exercise program. Methods We performed a 24-week randomized controlled feasibility study comparing aerobic exercise plus optimal medical management to medical management alone in patients with type 2 diabetes, obesity (body mass index [BMI] > 30 kg/m2), and stage 2-4 CKD (estimated glomerular filtration rate [eGFR] 15-90 mL/min/1.73 m2 with persistent proteinuria). Subjects randomized to exercise underwent thrice weekly aerobic training for 6 followed by 18 weeks of supervised home exercise. The primary outcome variable was change in proteinuria. Results Seven subjects randomized to exercise and 4 control subjects completed the study. Exercise training resulted in an increase in exercise duration during treadmill testing, which was accompanied by slight but insignificant decreases in resting systolic blood pressure and 24-hour proteinuria. Exercise did not alter GFR, hemoglobin, glycated hemoglobin, serum lipids, or C-reactive protein (CRP). Caloric intake and body weight and composition also did not change with exercise training. Conclusion Exercise training in obese diabetic patients with CKD is feasible and may have clinical benefits. A large-scale randomized controlled trial to determine the effects of exercise on renal functions, cardiovascular fitness, inflammation, and oxidative stress in diabetic patients with CKD is planned. PMID:20003224

  14. [Effects of various food products on blood sugar level in patients with diabetes mellitus and obesity].

    PubMed

    Kurbanov, S K; Khasaev, A Sh; Gapparov, M M

    1991-01-01

    The blood sugar level was evaluated in patients with insulin-independent diabetes mellitus and obesity, and in normal volunteers, during 3 h with a 30-min interval before and after food loading containing 50 g of carbohydrates. It has been found that 17 food products studied produce varying effects on the blood glucose level regardless of the content of starch and sugars in them. Pure glucose, boiled rice, potatoe, white bread, boiled bean, pastry, honey and sugar produce the highest glycemic effect. Milk, ice cream, boiled lens and noodles produce a moderate effect on the blood sugar level both in normal subjects and in patients with diabetes mellitus and obesity. The increase of the glucose blood level after intake of food products was significantly higher in patients with diabetes mellitus as compared to those with obesity and normal volunteers. Milk products, lens, macaroni and millet are most promising for patients with diabetes mellitus due to their moderate influence on the blood glucose content. PMID:2042318

  15. Virtual Reality and Interactive Gaming Technology for Obese and Diabetic Children: Is Military Medical Technology Applicable?

    PubMed Central

    Talbot, Major Thomas “Brett”

    2011-01-01

    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. PMID:21527087

  16. 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. PMID:21527087

  17. 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

  18. 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

  19. PRAS40 prevents development of diabetic cardiomyopathy and improves hepatic insulin sensitivity in obesity

    PubMed Central

    Völkers, Mirko; Doroudgar, Shirin; Nguyen, Nathalie; Konstandin, Mathias H; Quijada, Pearl; Din, Shabana; Ornelas, Luis; Thuerauf, Donna J; Gude, Natalie; Friedrich, Kilian; Herzig, Stephan; Glembotski, Christopher C; Sussman, Mark A

    2014-01-01

    Diabetes is a multi-organ disease and diabetic cardiomyopathy can result in heart failure, which is a leading cause of morbidity and mortality in diabetic patients. In the liver, insulin resistance contributes to hyperglycaemia and hyperlipidaemia, which further worsens the metabolic profile. Defects in mTOR signalling are believed to contribute to metabolic dysfunctions in diabetic liver and hearts, but evidence is missing that mTOR activation is causal to the development of diabetic cardiomyopathy. This study shows that specific mTORC1 inhibition by PRAS40 prevents the development of diabetic cardiomyopathy. This phenotype was associated with improved metabolic function, blunted hypertrophic growth and preserved cardiac function. In addition PRAS40 treatment improves hepatic insulin sensitivity and reduces systemic hyperglycaemia in obese mice. Thus, unlike rapamycin, mTORC1 inhibition with PRAS40 improves metabolic profile in diabetic mice. These findings may open novel avenues for therapeutic strategies using PRAS40 directed against diabetic-related diseases. PMID:24408966

  20. Ezetimibe improves hepatic steatosis in relation to autophagy in obese and diabetic rats

    PubMed Central

    Chang, Eugene; Kim, Lisa; Park, Se Eun; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Park, Cheol-Young

    2015-01-01

    AIM: To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes. METHODS: Male age-matched lean control LETO and obese and diabetic OLETF rats were administered either PBS or ezetimibe (10 mg/kg per day) via stomach gavage for 20 wk. Changes in weight gain and energy intake were regularly monitored. Blood and liver tissue were harvested after overnight fasting at the end of study. Histological assessment was performed in liver tissue. The concentrations of glucose, insulin, triglycerides (TG), free fatty acids (FFA), and total cholesterol (TC) in blood and TG, FFA, and TG in liver tissue were measured. mRNA and protein abundance involved in autophagy was analyzed in the liver. To investigate the effect of ezetimibe on autophagy and reduction in hepatic fat accumulation, human Huh7 hepatocytes were incubated with ezetimibe (10 μmol/L) together with or without palmitic acid (PA, 0.5 mmol/L, 24 h). Transmission electron microscopy (TEM) was employed to demonstrate effect of ezetimibe on autophagy formation. Autophagic flux was measured with bafilomycin A1, an inhibitor of autophagy and following immunoblotting for autophagy-related protein expression. RESULTS: In the OLETF rats that received ezetimibe (10 mg/kg per day), liver weight were significantly decreased by 20% compared to OLETF control rats without changes in food intake and body weight (P < 0.05). Lipid parameters including TG, FFA, and TC in liver tissue of ezetimibe-administrated OLETF rats were dramatically decreased at least by 30% compared to OLETF controls (P < 0.01). The serum glucose, insulin, HOMA-IR, and lipid profiles were also improved by ezetimibe (P < 0.05). In addition, autophagy-related mRNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3 (LC3) were significantly increased in the liver in rats that received ezetimibe (P < 0.05). Likewise, for hepatocytes

  1. 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

  2. Everything in Moderation--Dietary Diversity and Quality, Central Obesity and Risk of Diabetes.

    PubMed

    Otto, Marcia C de Oliveira; 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 better

  3. Rates of Complications and Mortality in Older Diabetes Patients: The Diabetes and Aging Study

    PubMed Central

    Huang, Elbert S.; Laiteerapong, Neda; Liu, Jennifer Y.; John, Priya M.; Moffet, Howard H.; Karter, Andrew J.

    2014-01-01

    Importance In the coming decades, the population of older adults with diabetes is expected to grow substantially. Understanding the clinical course of diabetes in this population is critical for establishing evidence-based clinical practice recommendations, research priorities, allocating resources, and setting health policies. Objective Contrast rates of diabetes complications and mortality across age and diabetes duration categories. Design, Setting, Participants This cohort study (2004–2010) included 72,310 older (≥60 years of age) patients with type 2 diabetes enrolled in a large, integrated healthcare delivery system. Incidence densities (events per 1000 person-years (pys)) were calculated for each age category (60s, 70s, 80+ years) and duration of diabetes (shorter: 0–9 years vs. longer: 10+ years). Main Outcome Measures Incident acute hyperglycemic events, acute hypoglycemic events (hypoglycemia), microvascular complications [end-stage renal disease (ESRD), peripheral vascular disease, lower extremity amputation, advanced eye disease], cardiovascular complications [coronary artery disease (CAD), cerebrovascular disease (CVD), congestive heart failure (CHF)], and all-cause mortality. Results Among older adults with diabetes of short duration, cardiovascular complications followed by hypoglycemia were the most common non-fatal complications. For example, among 70–79 year olds with short duration of diabetes, CAD and hypoglycemia rates were higher (11.5 and 5.0/1000 pys respectively), compared to ESRD (2.6/1000), amputation (1.3/1000), and acute hyperglycemic events (0.8/1000). We observed a similar pattern among subjects in the same age group with long diabetes duration where CAD and hypoglycemia had some of the highest incidence rates (19.0 and 15.9 /1000 pys respectively), compared to ESRD (7.6/1000), amputation (4.3/1000), and acute hyperglycemic events (1.8/1000). For a given age group, rates of each outcome, particularly hypoglycemia and

  4. 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

  5. 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

  6. 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

  7. 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

  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. 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

  11. 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…

  12. 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

  13. Betatrophin expression is promoted in obese hyperinsulinemic type 2 but not type 1 diabetic mice.

    PubMed

    Li, EnXu; Nakata, Masanori; Shinozaki, Atsumi; Yang, Yifei; Zhang, Boyang; Yada, Toshihiko

    2016-07-30

    Regeneration of pancreatic β-cell mass benefits both type 1 and type 2 diabetic patients. A recent study identified betatrophin as a β-cell proliferation factor. However, the expressional regulation of betatrophin remains less defined. In this study, we aimed to clarify the regulation of betatrophin expression in obese type 2 vs. type 1 diabetes model animals. We experimented type 2 diabetes models, diet-induced-obesity (DIO) mice and db/db mice, and type 1 diabetes models, C57B6 mice receiving streptozotocin (STZ) or 70% pancreatectomy to destroy or remove β-cells. Serum betatrophin levels and betatrophin mRNA expressions in the liver, white adipose tissue (WAT) and brown adipose tissue (BAT) were measured. In DIO mice and db/db mice, serum betatrophin and betatrophin mRNA expressions in the liver, WAT and BAT were elevated in parallel with increases in body weight and plasma insulin. These elevated betatrophin mRNA expressions were not altered by treatment with SGLT2 inhibitor that ameliorated hyperglycemia. In pancreatectomized mice, betatrophin expression in WAT decreased in parallel with reductions in weight and insulin. In STZ-treated mice, betatrophin expressions in the liver, WAT and BAT were reduced. However, when the mouse liver slices were cultured with STZ, betatrophin expression was significantly reduced, indicating a direct action of STZ on the liver. These results indicate that the expression of betatrophin is upregulated in the liver, WAT and BAT in obese hyperinsulinemic type 2 diabetes but decreased in WAT in hypoinsulinemic type 1 diabetes, suggesting its positive correlation with body weight and plasma insulin but not blood glucose. PMID:27097546

  14. Cell-mediated immunity to pancreatic islet cells in the non-obese diabetic (NOD) mouse: in vitro characterization and time course study.

    PubMed Central

    Timsit, J; Debray-Sachs, M; Boitard, C; Bach, J F

    1988-01-01

    The non-obese diabetic (NOD) mouse is an animal model of insulin-dependent diabetes mellitus (IDDM), in which 80% of the females become diabetic after the age of 12 weeks. Using an in vitro assay we investigated the capacity of spleen lymphocytes from NOD mice to inhibit the insulin secretion of normal islet cells after stimulation by theophylline plus arginine. Spleen cells from diabetic NOD mice inhibited the insulin release of DBA/2 islet cells. Depletion experiments using monoclonal antibodies demonstrated that inhibitory cells belonged to the Lyt2 positive T lymphocyte subset. The phenomenon was not restricted by the MHC class I K region, shared by NOD and DBA/2 mice, since lymphocytes from diabetic NOD mice also inhibited the insulin secretion of normal Wistar rat islet cells. Inhibitory T cells were detected in overtly diabetic mice but also in non-diabetic females aged 5-11 weeks indicating that they are not secondary to metabolic disturbances and might contribute to their onset. Conversely they were not found in male NOD mice although some of these mice show insulitis. The presence of these inhibitory T cells might thus represent an early and sensitive marker of anti-islet cell-mediated autoimmunity. PMID:3052943

  15. Effect of obesity on the reliability of age-at-death indicators of the pelvis.

    PubMed

    Wescott, Daniel J; Drew, Jessica L

    2015-04-01

    During medicolegal investigations, forensic anthropologists commonly use morphological changes in the auricular surface of the ilium and the symphyseal face of the pubis to estimate age. However, obesity may impact the reliability of age estimations based on pelvic joints. Over the past several decades, the prevalence of obesity has dramatically increased in the United States (US). Since the rate of progression through age-related stages of weight-bearing joints may be influenced by excessive body mass, it is important that anthropologists understand how obesity affects age-related morphological changes in the skeleton. This study investigates the effects of obesity on the validity of the estimated age-at-death based on the Buckberry-Chamberlin and Suchey-Brooks methods by comparing US adults considered normal BMI (BMI 18.5-24.9) and obese (BMI ≥ 30). The obese group exhibits overall greater bias (overestimation of age) and inaccuracy, less precision, and lower correlations between estimated and known age than the normal BMI group using both methods, although differences in the pubic symphysis are not statistically significant. For the auricular surface the age of transition from one phase to the next is lower and the standard deviations are greater for the obese as compared to normal weight individuals. This study helps to elucidate how obesity affects the rate of age-related skeletal change of the human pelvis, and shows that the pubic symphysis may be a more reliable indicator of age in obese individuals and that greater standard deviations are needed for obese individuals when estimating age-at-death from the pelvis. PMID:25447813

  16. Prevalence of obesity, central obesity and the associated factors in urban population aged 20-70 years, in the north of Iran: a population-based study and regression approach.

    PubMed

    Hajian-Tilaki, K O; Heidari, B

    2007-01-01

    , history of parental obesity and parity > or =5 were associated with increased risk of obesity (OR = 2.2, P < 0.001 and OR = 2.43, P < 0.0001 and OR = 3.73, P < 0.0001 respectively). The results of this study indicate an increased rate of obesity and overweigh in the north population of Iran. With respect to these findings, low level of activity and education, parity, family history of obesity, marriage at earlier age and ageing are responsible for both obesity and central obesity in the north of Iran. Therefore, a community-based multiple strategies are required to combat with increasing rate of obesity and its subsequent complications such as diabetes, coronary artery disease, hypertension and osteoarthritis. PMID:17212790

  17. 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. PMID:26854707

  18. Clinical importance of assessment of type 2 diabetes mellitus with visceral obesity. A Japanese perspective.

    PubMed

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

    2012-03-01

    Type 2 diabetes mellitus (T2DM) is a complex heterogeneous group of metabolic disorders including hyperglycemia and impaired insulin action and/or insulin secretion. Obesity T2DM has become a serious problem in Japan as in Western countries, with over-eating and physical inactivity. Obese Asians have mild degree of adiposity, compared with Western subjects. Unlike total body fat, body fat distribution, especially excess accumulation of visceral fat, correlates with various diabetogenic, atherogenic, prothrombotic and proinflammatory metabolic abnormalities, which increase the risk of atherosclerotic cardiovascular disease (ACVD). Obese patients with T2DM have poor glycemic control with disordered eating behaviors, and complications of hypertension and dyslipidemia, leading to ACVD. The major therapies in obese T2DM, hyperinsulinemia and low insulin sensitivity, available for weight loss, especially visceral fat reduction, include caloric restriction, physical activity and behavior modification. On the other hand, the major therapies in non-obese T2DM with insufficient insulin secretion, are insulin-secretory agents and injectable insulin. For clinically meaningful prevention/reduction in the rate of future ACVD in T2DM, it may be important to stratify T2DM subjects into those with and without visceral obesity and design specific management protocols for each group. PMID:22309596

  19. 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

  20. 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

  1. 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. PMID:26774185

  2. 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

  3. Nutraceutical effects of fucoxanthin for obesity and diabetes therapy: a review.

    PubMed

    Maeda, Hayato

    2015-01-01

    Obesity, which results from an imbalance between energy intake and energy expenditure, has become a major health risk factor worldwide, causing numerous and various diseases such as diabetes, hypertension, and cardiovascular diseases. Fucoxanthin, a specific carotenoid in brown algae, has garnered much attention for its anti-obesity and anti-diabetic effects attributable to a unique mechanism. Fucoxanthin induces uncoupling protein 1 (UCP1) expression in white adipose tissue (WAT). That inner membrane mitochondrial protein, UCP1, can dissipate energy through oxidation of fatty acids and heat production. Furthermore, fucoxanthin improves insulin resistance and ameliorates blood glucose levels through down-regulation of adipocytokines related to insulin resistance in WAT and up-regulation of glucose transporter 4 (GLUT4) in skeletal muscle. Algae fucoxanthin is a beneficial compound for the prevention of the metabolic syndrome. PMID:25748372

  4. 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

  5. The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

    PubMed Central

    Lewitt, Moira S.; Dent, Mairi S.; Hall, Kerstin

    2014-01-01

    The insulin-like growth factor (IGF) system, acting in concert with other hormone axes, is important in normal metabolism. In obesity, the hyperinsulinaemia that accompanies peripheral insulin resistance leads to reduced growth hormone (GH) secretion, while total IGF-I levels are relatively unchanged due to increased hepatic GH sensitivity. IGF-binding protein (IGFBP)-1 levels are suppressed in relation to the increase in insulin levels in obesity and low levels predict the development of type 2 diabetes several years later. Visceral adiposity and hepatic steatosis, along with a chronic inflammation, contribute to the IGF system phenotype in individuals with metabolic syndrome and type 2 diabetes mellitus, including changes in the normal inverse relationship between IGFBP-1 and insulin, with IGFBP-1 concentrations that are inappropriately normal or elevated. The IGF system is implicated in the vascular and other complications of these disorders and is therefore a potential therapeutic target. PMID:26237614

  6. 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. PMID:23781992

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Patterns of Obesity Development before the Diagnosis of Type 2 Diabetes: The Whitehall II Cohort Study

    PubMed Central

    Vistisen, Dorte; Witte, Daniel R.; Tabák, Adam G.; Herder, Christian; Brunner, Eric J.; Kivimäki, Mika; Færch, Kristine

    2014-01-01

    Background Patients with type 2 diabetes vary greatly with respect to degree of obesity at time of diagnosis. To address the heterogeneity of type 2 diabetes, we characterised patterns of change in body mass index (BMI) and other cardiometabolic risk factors before type 2 diabetes diagnosis. Methods and Findings We studied 6,705 participants from the Whitehall II study, an observational prospective cohort study of civil servants based in London. White men and women, initially free of diabetes, were followed with 5-yearly clinical examinations from 1991–2009 for a median of 14.1 years (interquartile range [IQR]: 8.7–16.2 years). Type 2 diabetes developed in 645 (1,209 person-examinations) and 6,060 remained free of diabetes during follow-up (14,060 person-examinations). Latent class trajectory analysis of incident diabetes cases was used to identify patterns of pre-disease BMI. Associated trajectories of cardiometabolic risk factors were studied using adjusted mixed-effects models. Three patterns of BMI changes were identified. Most participants belonged to the “stable overweight” group (n = 604, 94%) with a relatively constant BMI level within the overweight category throughout follow-up. They experienced slightly worsening of beta cell function and insulin sensitivity from 5 years prior to diagnosis. A small group of “progressive weight gainers” (n = 15) exhibited a pattern of consistent weight gain before diagnosis. Linear increases in blood pressure and an exponential increase in insulin resistance a few years before diagnosis accompanied the weight gain. The “persistently obese” (n = 26) were severely obese throughout the whole 18 years before diabetes diagnosis. They experienced an initial beta cell compensation followed by loss of beta cell function, whereas insulin sensitivity was relatively stable. Since the generalizability of these findings is limited, the results need confirmation in other study populations. Conclusions Three

  13. 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. PMID:26464517

  14. Metabolic Mechanisms in Obesity and Type 2 Diabetes: Insights from Bariatric/Metabolic Surgery.

    PubMed

    Cătoi, Adriana Florinela; Pârvu, Alina; Mureşan, Adriana; Busetto, Luca

    2015-01-01

    Obesity and the related diabetes epidemics represent a real concern worldwide. Bariatric/metabolic surgery emerged in last years as a valuable therapeutic option for obesity and related diseases, including type 2 diabetes mellitus (T2DM). The complicated network of mechanisms involved in obesity and T2DM have not completely defined yet. There is still a debate on which would be the first metabolic defect leading to metabolic deterioration: insulin resistance or hyperinsulinemia? Insight into the metabolic effects of bariatric/metabolic surgery has revealed that, beyond weight loss and food restriction, other mechanisms can be activated by the rearrangements of the gastrointestinal tract, such as the incretinic/anti-incretinic system, changes in bile acid composition and flow, and modifications of gut microbiota; all of them possibly involved in the remission of T2DM. The complete elucidation of these mechanisms will lead to a better understanding of the pathogenesis of this disease. Our aim was to review some of the metabolic mechanisms involved in the development of T2DM in obese patients as well as in the remission of this condition in patients submitted to bariatric/metabolic surgery. PMID:26584027

  15. Deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice

    PubMed Central

    Liu, Jian; Divoux, Adeline; Sun, Jiusong; Zhang, Jie; Clément, Karine; Glickman, Jonathan N.; Sukhova, Galina K.; Wolters, Paul J.; Du, Juan; Gorgun, Cem Z.; Doria, Alessandro; Libby, Peter; Blumberg, Richard S.; Kahn, Barbara B.; Hotamisligil, Gokhan S.; Shi, Guo-Ping

    2009-01-01

    Although mast cell functions classically relate to allergic responses1–3, recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm, and cancer4–8. This study presents evidence that mast cells contribute importantly to diet-induced obesity and diabetes. White adipose tissues (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Genetically determined mast cell deficiency and pharmacological stabilization of mast cells in mice reduce body weight gain and levels of inflammatory cytokines, chemokines, and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer of cytokine-deficient mast cells established that these cells contribute to mice adipose tissue cysteine protease cathepsin expression, apoptosis, and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance by production of IL6 and IFN-γ. Mast cell stabilizing agents in clinical use reduced obesity and diabetes in mice, suggesting the potential of developing novel therapies for these common human metabolic disorders. PMID:19633655

  16. 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. PMID:26979523

  17. 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.

  18. Elevated IgG levels against specific bacterial antigens in obese patients with diabetes and in mice with diet-induced obesity and glucose intolerance.

    PubMed

    Mohammed, Nadeem; Tang, Lihua; Jahangiri, Anisa; de Villiers, Willem; Eckhardt, Erik

    2012-09-01

    High fat diets increase the risk for insulin resistance by promoting inflammation. The cause of inflammation is unclear, but germfree mouse studies have implicated commensal gut bacteria. We tested whether diet-induced obesity, diabetes, and inflammation are associated with anti-bacterial IgG. Blood from lean and obese healthy volunteers or obese patients with diabetes were analyzed by ELISA for IgG against extracts of potentially pathogenic and pro-biotic strains of Escherichia coli (LF-82 and Nissle), Bacteroides thetaiotaomicron, and Lactobacillus acidophilus, and for circulating tumor necrosis factor α (TNFα). C57Bl/6 mice were fed low- or high-fat diets (10% or 60% kcal from fat) for 10 weeks and tested for anti-bacterial IgG, bodyweight, fasting glucose, and inflammation. Obese diabetic patients had significantly more IgG against extracts of E. coli LF-82 compared with lean controls, whereas IgG against extracts of the other bacteria was unchanged. Circulating TNFα was elevated and correlated with IgG against the LF-82 extract. Mice fed high-fat diets had increased fasting glucose levels, elevated TNFα and neutrophils, and significantly more IgG against the LF-82 extracts. Diabetes in obesity is characterized by increased IgG against specific bacterial antigens. Specific commensal bacteria may mediate inflammatory effects of high-fat diets. PMID:22424821

  19. The role of gut microbiota in the development of type 1, obesity and type 2 diabetes mellitus

    PubMed Central

    Tai, Ningwen; Wong, F. Susan; Wen, Li

    2015-01-01

    Diabetes is a group of metabolic disorders characterized by persistent hyperglycemia and has become a major public health concern. Autoimmune type 1 diabetes (T1D) and insulin resistant type 2 diabetes (T2D) are the two main types. A combination of genetic and environmental factors contributes to the development of these diseases. Gut microbiota have emerged recently as an essential player in the development of T1D, obesity and T2D. Altered gut microbiota have been strongly linked to disease in both rodent models and humans. Both classic 16S rRNA sequencing and shot-gun metagenomic pyrosequencing analysis have been successfully applied to explore the gut microbiota composition and functionality. This review focuses on the association between gut microbiota and diabetes and discusses the potential mechanisms by which gut microbiota regulate disease development in type 1 diabetes, obesity and type 2 diabetes. PMID:25619480

  20. 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

  1. 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

  2. Charting weight four times daily as an effective behavioural approach to obesity in patients with type 2 diabetes.

    PubMed

    Yamada, Tomohide; Kiuchi, Yuka; Nemoto, Mitsuru; Yamashita, Shigeo

    2014-03-01

    Although many obese people successfully lose weight by dieting and/or behavioural therapy, most of them subsequently regain the lost weight. Thus, new therapeutic strategies are required to maintain weight loss. We report a woman with type 2 diabetes and moderate obesity who succeeded in achieving good glycaemic control and long-term weight loss with weaning from insulin therapy, while charting her weight four times daily. This charting method might be useful for long-term maintenance of weight reduction in obese diabetic patients. Obese patients can monitor their irregular weight fluctuations produced by overeating and correct both their food intake and their lifestyle. Further studies, including randomized control trials, will be needed to confirm the efficacy of this approach in patients with type 2 diabetes. PMID:24227536

  3. Oral insulin (human, murine, or porcine) does not prevent diabetes in the non-obese diabetic mouse.

    PubMed

    Pham, Minh N; Gibson, Claire; Rydén, Anna K E; Perdue, Nikole; Boursalian, Tamar E; Pagni, Philippe P; Coppieters, Ken; Skonberg, Christian; Porsgaard, Trine; von Herrath, Matthias; Vela, Jose Luis

    2016-03-01

    Studies have shown oral insulin prevents type 1 diabetes (T1D) in mouse models, however human trials were inconclusive. We tested the ability of different insulins to prevent T1D in non-obese diabetic mice. Mice received oral insulin or PBS twice weekly and disease was monitored. Contrary to previous studies, no insulin tested showed significant ability to prevent T1D, nor did testing of linked suppression in a delayed type hypersensitivity model have reproducible effect. To investigate delivery of antigen within the GI tract, blue dye was fed to mice. Dye traveled 5-8 cm from stomach to small intestine within 10s, suggesting orally administered antigen may not get digested in the stomach in mice. Insulin incubated with jejunum extracts was instantly digested. Thus, in humans large doses of insulin may be required to achieve tolerance as antigen may be more vulnerable to digestion in the stomach even before reaching the small intestine. PMID:26821303

  4. Correlative studies on the effects of obesity, diabetes and hypertension on gene expression in omental adipose tissue of obese women

    PubMed Central

    Fain, J N

    2011-01-01

    Objective: A major consequence of obesity is the enormous expansion of and enhanced inflammatory response seen in visceral adipose tissue. I hypothesized that the expression of inflammatory markers in visceral omental fat would correlate with the extent of visceral adiposity as measured by waist circumference or body mass index and that diabetes and hypertension, defined as subjects taking anti-hypertensive drugs, would be associated with changes in mRNA expression in visceral fat. Design and methods: The expression of 106 mRNAs by RT-PCR was examined in observational studies using extracts of omental fat of obese women undergoing bariatric surgery as well as the circulating levels of some adipokines. We also compared the mRNA levels of 65 proteins in omental fat removed during gastric bypass surgery of women with and without hypertension and those with type 2 diabetes. Results: Out of 106 mRNAs the expression of 10 mRNAs in omental fat of women not taking anti-hypertensive drugs correlated with waist circumference while 7 different mRNAs had significant correlations with circulating glucose. The correlations of waist circumference with mRNA expression were abolished, except for interleukin (IL)-1 receptor antagonist (IL-1RA), in women taking anti-hypertensive drugs. The correlations of blood glucose with omental fat mRNA expression were abolished, except for that of Akt1 and Akt2, in women taking anti-hypertensive drugs. However, the expression of 4 different mRNAs in omental fat was affected by circulating glucose in subjects taking anti-hypertensive drugs. The circulating levels of IL-1 RA, but not fatty acid binding protein 4, adipsin and phospholipase A2, correlated with both waist circumference and mRNA expression in omental fat. Conclusion: In female bariatric surgery patients, the mRNA expression of some proteins in omental fat was affected by the degree of obesity, whereas hypertension and diabetes affected a separate set of mRNAs. PMID:23154658

  5. 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

  6. Clinical analysis of endometrial cancer patients with obesity, diabetes, and hypertension

    PubMed Central

    Yin, Xiang-Hua; Jia, Hong-Yan; Xue, Xiao-Rui; Yang, Shi-Zhang; Wang, Zhong-Qin

    2014-01-01

    The purpose of our study was to study the postoperation outcome and incidence of deep vein thrombosis (DVT) in endometrial cancer (EC) patients with or without hypertension, diabetes, and obesity. This analysis included 219 patients with endometrial carcinoma who were treated between 2002 and 2012 at the Department of Obstetrics and Gynecology, Yangzhou University Hospital. Patients were divided into five groups based on the comorbidities. Group 1 EC & Diabetes, Group 2 EC & Hypertension, Group 3 EC & Obesity, Group 4 EC Combined two, Group 5 no combined. Then the five groups were analyzed in postoperation outcomes and DVT incidence using one-way analysis of variance or Pearson χ2 tests. we found that there was no significant difference in pelvic lymph node metastasis (P=0.102), aortic lymph node metastasis (P=0.221), and operative time (P=0.503). But there was significant difference in blood loss (P<0.01), hospital stay (P<0.01). No significant difference (P>0.05) in treatment outcome between surgical operation, surgical operation+ radiotherapy and radiotherapy. Deep vein thrombosis and pulmonary embolism have some significantly (P<0.01) (P<0.01), respectively. Compared to patients who simply suffer from endometrial cancer, diabetes make patients easy bleeding in surgery and increase hospitalization time in corresponding. VTE is a common complication of EC surgery with comorbidities, such as diabetes and hypertension, and it’s a remarkable proportion of events occurring late after surgery. PMID:24753771

  7. 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 ...

  8. Exenatide improves excessive daytime sleepiness and wakefulness in obese patients with type 2 diabetes without obstructive sleep apnoea.

    PubMed

    Idris, Iskandar; Abdulla, Haitham; Tilbrook, Sean; Dean, Roy; Ali, Nabeel

    2013-02-01

    We investigate the effects of exenatide on excessive daytime sleepiness (EDS), driving performance and depression score in patients with type 2 diabetes with EDS. Eight obese patients with diabetes but without obstructive sleep apnoea (OSA) participated in a placebo-controlled single-blind study during which multiple wakefulness and sleep latency test, Epworth score, driving performance, depression score, fasting glucose and glycated haemoglobin (HbA1c) levels were assessed at baseline, end of placebo and treatment phase at baseline and after 22 weeks of treatment. Mean (±standard error of the mean) age, body mass index (kg m(2) ) and HbA1c [mmol mol(-1) (%)] of patients at baseline were 50 ± 4.9 years, 37.6 ± 1.1 and 65 ± 19 (8.06 ± 0.41), respectively. When compared to placebo, exenatide treatment was associated with a decrease in both subjective and objective sleepiness, based on the Epworth score reduction and the sleep latency increase assessed by multiple objective sleepiness and sustained attention (OSLER) tests, respectively. Mean sleep latency time (adjusted for change in HbA1c and weight) were 32.1 ± 1.7, 29.1 ± 1.7 and 37.7 ± 1.7, respectively (P = 0.002). Modelling for covariates suggested that improvement in mean sleep latency time is predicted by changes in weight (P = 0.003), but not by changes in HbA1c (P = 0.054). Epworth sleepiness score was reduced significantly (values for placebo versus exenatide: 11.3 ± 1.2 versus 5.7 ± 1.3; P = 0.003). No significant change was noted in the depression score and driving performance. Exenatide is associated with a significant reduction in objective sleepiness in obese patients with type 2 diabetes without OSA, independent of HbA1c levels. These findings could form a basis for further studies to investigate the pathophysiological mechanisms of sleepiness in obese patients with type 2 diabetes. PMID:22716195

  9. Feasibility of Adolescents to Conduct Community-Based Participatory Research on Obesity and Diabetes in Rural Appalachia

    PubMed Central

    Bardwell, Genevieve; Morton, Cathy; Chester, Ann; Pancoska, Petr; Buch, Shama; Cecchetti, Alfred; Vecchio, Marcella; Paulsen, Stephanie; Groark, Stephen; Branch, Robert A.

    2015-01-01

    Community-Based Participatory Research (CBPR) has been advocated to translate advances in health care sciences to the community. We describe a novel approach applied to obesity management and diabetes prevention. This takes advantage of a network of science clubs organized by the Health Sciences and Technology Academy (HSTA) for extracurricular activity of disadvantaged high school students in rural Appalachia. Physician scientists and educators provided an intensive summer course on CBPR, ethics, and study design on obesity management and diabetes prevention. Ethical certification for CBPR investigation was obtained for 210 students and 18 mentors for a study on the prevalence of obesity and Type II diabetes within their community. Over a 6-month period, 989 had a collection of complete analyzable data, of which 103 had diabetes. The proportion with obesity (BMI ≥ 30) was over 50%. The frequency of diabetes was related to increasing BMI. When BMI ≥ 40, the frequency approached 50%, and exhibited a clear familial distribution. We conclude that trained adolescents can effectively conduct CBPR, and obesity and diabetes are more prevalent than previously reported in this community. This experience provides encouragement to conduct future studies to influence weight management from high-risk populations in this medically disadvantaged community. PMID:20443917

  10. 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. PMID:25284929

  11. Protective Effect of Gymnema sylvestre Ethanol Extract on High Fat Diet-induced Obese Diabetic Wistar Rats

    PubMed Central

    Kumar, V.; Bhandari, Uma; Tripathi, C. D.; Khanna, Geetika

    2014-01-01

    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. PMID:25284929

  12. 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

  13. The role of AGEs and AGE inhibitors in diabetic cardiovascular disease.

    PubMed

    Thomas, M C; Baynes, J W; Thorpe, S R; Cooper, M E

    2005-06-01

    Prolonged hyperglycemia, dyslipidemia and oxidative stress in diabetes result in the production and accumulation of AGEs. It is now clear that AGEs contribute to the development and progression of cardiovascular disease in diabetes, as well as other complications. AGEs are thought to act through receptor-independent and dependent mechanisms to promote vascular damage, fibrosis and inflammation associated with accelerated atherogenesis. As a result, novel therapeutic agents to reduce the accumulation of AGEs in diabetes have gained interest as potential cardioprotective approaches. A variety of agents have been developed which are examined in detail in this review. These include aminoguanidine, ALT-946, pyridoxamine, benfotiamine, OPB-9195, alagebrium chloride, N-phenacylthiazolium bromide and LR-90. In addition, it has been demonstrated that a number of established therapies have the ability to reduce the accumulation of AGEs in diabetes including ACE inhibitors, angiotensin receptor antagonists, metformin, peroxisome proliferators receptor agonists, metal chelators and some antioxidants. The fact that many of these inhibitors of AGEs are effective in experimental models, despite their disparate mechanisms of action, supports the keystone role of AGEs in diabetic vascular damage. Nonetheless, the clinical utility of AGE inhibition remains to be firmly established. Optimal metabolic and blood pressure control, that is achieved early and sustained indefinitely, remains the best recourse for inhibition of AGEs until more specific interventions become a clinical reality. PMID:16026265

  14. 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

  15. Association of Metabolites with Obesity and Type 2 Diabetes Based on FTO Genotype

    PubMed Central

    Kim, Yun Kyoung; Park, Suyeon; Kim, Jeong-Min; Yun, Jun Ho; Yu, Ho-Yeong; Kim, Bong-Jo

    2016-01-01

    The single nucleotide polymorphism rs9939609 of the gene FTO, which encodes fat mass and obesity–associated protein, is strongly associated with obesity and type 2 diabetes (T2D) in multiple populations; however, the underlying mechanism of this association is unclear. The present study aimed to investigate FTO genotype–dependent metabolic changes in obesity and T2D. To elucidate metabolic dysregulation associated with disease risk genotype, genomic and metabolomic datasets were recruited from 2,577 participants of the Korean Association REsource (KARE) cohort, including 40 homozygous carriers of the FTO risk allele (AA), 570 heterozygous carriers (AT), and 1,967 participants carrying no risk allele (TT). A total of 134 serum metabolites were quantified using a targeted metabolomics approach. Through comparison of various statistical methods, seven metabolites were identified that are significantly altered in obesity and T2D based on the FTO risk allele (adjusted p < 0.05). These identified metabolites are relevant to phosphatidylcholine metabolic pathway, and previously reported to be metabolic markers of obesity and T2D. In conclusion, using metabolomics with the information from genome-wide association studies revealed significantly altered metabolites depending on the FTO genotype in complex disorders. This study may contribute to a better understanding of the biological mechanisms linking obesity and T2D. PMID:27249024

  16. 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

  17. Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes

    PubMed Central

    Kimple, Michelle E; Neuman, Joshua C; Linnemann, Amelia K; Casey, Patrick J

    2014-01-01

    The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology. PMID:24946790

  18. Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes.

    PubMed

    Kimple, Michelle E; Neuman, Joshua C; Linnemann, Amelia K; Casey, Patrick J

    2014-01-01

    The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology. PMID:24946790

  19. Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity.

    PubMed

    Oh, Chang Myung; Park, Sangkyu; Kim, Hail

    2016-04-01

    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

  20. Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients

    PubMed Central

    Magalhaes, Isabelle; Pingris, Karine; Poitou, Christine; Bessoles, Stéphanie; Venteclef, Nicolas; Kiaf, Badr; Beaudoin, Lucie; Da Silva, Jennifer; Allatif, Omran; Rossjohn, Jamie; Kjer-Nielsen, Lars; McCluskey, James; Ledoux, Séverine; Genser, Laurent; Torcivia, Adriana; Soudais, Claire; Lantz, Olivier; Boitard, Christian; Aron-Wisnewsky, Judith; Larger, Etienne; Clément, Karine; Lehuen, Agnès

    2015-01-01

    Obesity and type 2 diabetes (T2D) are associated with low-grade inflammation, activation of immune cells, and alterations of the gut microbiota. Mucosal-associated invariant T (MAIT) cells, which are innate-like T cells that recognize bacterial ligands, are present in blood and enriched in mucosal and inflamed tissues. Here, we analyzed MAIT cells in the blood and adipose tissues of patients with T2D and/or severe obesity. We determined that circulating MAIT cell frequency was dramatically decreased in both patient groups, and this population was even undetectable in some obese patients. Moreover, in both patient groups, circulating MAIT cells displayed an activated phenotype that was associated with elevated Th1 and Th17 cytokine production. In obese patients, MAIT cells were more abundant in adipose tissue than in the blood and exhibited a striking IL-17 profile. Bariatric surgery in obese patients not only improved their metabolic parameters but also increased circulating MAIT cell frequency at 3 months after surgery. Similarly, cytokine production by blood MAIT cells was strongly decreased after surgery. This study reveals profound MAIT cell abnormalities in patients harboring metabolic disorders, suggesting their potential role in these pathologies. PMID:25751065

  1. 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

  2. Detection of vasostatin-1-specific CD8(+) T cells in non-obese diabetic mice that contribute to diabetes pathogenesis.

    PubMed

    Nikoopour, E; Krougly, O; Lee-Chan, E; Mansour Haeryfar, S M; Singh, B

    2016-09-01

    Chromogranin A (ChgA) is an antigenic target of pathogenic CD4(+) T cells in a non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). Vasostatin-1 is a naturally processed fragment of ChgA. We have now identified a novel H2-K(d) -restricted epitope of vasostatin-1, ChgA 36-44, which elicits CD8(+) T cell responses in NOD mice. By using ChgA 36-44/K(d) tetramers we have determined the frequency of vasostatin-1-specific CD8(+) T cells in pancreatic islets and draining lymph nodes of NOD mice. We also demonstrate that vasostatin-1-specific CD4(+) and CD8(+) T cells constitute a significant fraction of islet-infiltrating T cells in diabetic NOD mice. Adoptive transfer of T cells from ChgA 36-44 peptide-primed NOD mice into NOD/severe combined immunodeficiency (SCID) mice led to T1D development. These findings indicate that vasostatin-1-specific CD8(+) T cells contribute to the pathogenesis of type 1 diabetes in NOD mice. PMID:27185276

  3. Risk of Developing Diabetes and Cardiovascular Disease in Metabolically Unhealthy Normal-Weight and Metabolically Healthy Obese Individuals

    PubMed Central

    Aung, KoKo; Hinojosa, Marco A.; Haffner, Steven M.

    2014-01-01

    Context: The risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) associated with obesity appears to be influenced by the coexistence of other metabolic abnormalities. Objective: We examined the risk of developing CVD and DM in metabolically healthy obese (MHO) and metabolically unhealthy normal weight (MUH-NW) individuals. Design and Setting: We analyzed prospective data of the San Antonio Heart Study, a population-based study among Mexican Americans and non-Hispanic whites (median follow-up, 7.4 y). Participants: Incident DM and CVD were assessed in 2814 and 3700 participants aged 25 to 64 years, respectively. Main Measures: MHO was defined as obesity (body mass index ≥ 30 kg/m2) with no more than one metabolic abnormality, and MUH-NW was defined as body mass index <25 kg/m2 with two or more abnormalities. Results: In logistic regression models, BMI was associated with incident DM after controlling for demographics, family history of DM, and fasting glucose (odds ratio × 1 SD, 1.7 [95% CI, 1.5–2.0]). Both MUH-NW and MHO individuals had an increased DM risk (2.5 [1.1–5.6] and 3.9 [2.0–7.4], respectively). Similarly, BMI was related to incident CVD after adjusting for demographics and Framingham risk score (1.3 [1.1–1.6]). Incident CVD was also increased in MUH-NW and MHO individuals (2.9 [1.3–6.4] and 3.9 [1.9–7.8], respectively). Results were consistent across gender and ethnic categories. Conclusion: The risk of developing DM and CVD is increased in MUH-NW and MHO individuals. Screening for obesity and other metabolic abnormalities should be routinely performed in clinical practice to institute appropriate preventive measures. PMID:24257907

  4. Bromodomain Coactivators in Cancer, Obesity, Type 2 Diabetes, and Inflammation

    PubMed Central

    Denis, Gerald V.

    2011-01-01

    Double bromodomain proteins bind to acetylated lysines in histones, bringing associated histone modification and nucleosome remodeling activity to chromatin. The ability of bromodomain regulators to alter chromatin status and control gene expression has long been appreciated to be important in the development of certain human cancers. However, bromodomain proteins have now been found also to be critical, non-redundant players in diverse, non-malignant phenotypes, directing transcriptional programs that control adipogenesis, energy metabolism and inflammation. The fact that such different processes are functionally linked by the same molecular machinery suggests a common epigenetic basis to understand and interpret the origins of several important co-morbidities, such as asthma or cancer that occurs in obesity, and complex inflammatory diseases like cardiovascular disease, systemic lupus erythematosus, rheumatoid arthritis and insulin resistance that may be built on a common pro-inflammatory foundation. PMID:21189220

  5. Genetic variants associated with lean and obese type 2 diabetes in a Han Chinese population

    PubMed Central

    Kong, Xiaomu; Xing, Xiaoyan; Hong, Jing; Zhang, Xuelian; Yang, Wenying

    2016-01-01

    Abstract Type 2 diabetes (T2D) is highly phenotypically heterogeneous. Genetics of the heterogeneity of lean and obese T2D is not clear. The aim of the present study was to identify the associations of T2D-related genetic variants with the risks for lean and obese T2D among the Chinese Han population. A case–control study consisting of 5338 T2D patients and 4663 normal glycemic controls of Chinese Han recruited in the Chinese National Diabetes and Metabolic Disorders Study was conducted. T2D cases were identified according to the 1999 World Health Organization criteria. Lean T2D was defined as T2D patient with a body mass index (BMI) <23 kg/m2, whereas obese T2D was defined as T2D patient with a BMI ≥28 kg/m2. Twenty-five genome-wide association studies previously validated T2D-related single-nucleotide polymorphisms (SNPs) were genotyped. A genotype risk score (GRS) based on the 25 SNPs was created. After adjusting for multiple covariates, SNPs in or near CDKAL1, CDKN2BAS, KCNQ1, TCF7L2, CDC123/CAMK1D, HHEX, and TCF2 were associated with the risk for lean T2D, and SNPs in or near KCNQ1 and FTO were associated with the risk for obese T2D. The results showed that the GRS for 25 T2D-related SNPs was more strongly associated with the risk for lean T2D (Ptrend = 2.66 × 10−12) than for obese T2D (Ptrend = 2.91 × 10−5) in our study population. Notably, the T2D GRS contributed to lower obesity-related measurements and greater β-cell dysfunction, including lower insulin levels in oral glucose tolerance test, decreased insulinogenic index, and Homeostasis Model Assessment for β-cell Function. In conclusion, our findings identified T2D-related genetic loci that contribute to the risk of lean and obese T2D individually and additively in a Chinese Han population. Moreover, the study highlights the contribution of known T2D genomic loci to the heterogeneity of lean and obese T2D in Chinese Hans. PMID:27281091

  6. Sex-Specific Prevalence of Diabetes and Cardiovascular Risk Factors in the Middle-Aged Population of China: A Subgroup Analysis of the 2007–2008 China National Diabetes and Metabolic Disorders Study

    PubMed Central

    Yang, Zhaojun; Xing, Xiaoyan; Zhao, Wenhui; Wang, Na; Xie, Lingding; Yang, Wenying

    2015-01-01

    The sex difference in the prevalence rates of diabetes and cardiovascular diseases (CVDs) among the middle-aged population in China remain largely unknown. Therefore, we analyzed differences in the prevalence of diabetes, self-reported CVDs, and some CVD risk factors among men and women in the middle-aged population (30–49 years) and in individuals aged 50 years and older using data from the China National Diabetes and Metabolic Disorders Study of 2007–2008. Middle-aged men appeared to have significantly a higher prevalence of diabetes and self-reported CVDs than middle-aged women (8.07% vs 5.06% for diabetes, P < 0.001; 0.64% vs 0.22% for CVDs, P < 0.001). Men also showed higher rates of central obesity, hypertension, and dyslipidemia than women (all P < 0.01). Compared with women, men were more likely to drink alcohol and smoke cigarettes but less likely to be under diet control. The sex-specific differences in prediabetes, CVD, and CVD risk factors between men and women were diminished or even reversed in the population aged 50 years and older. No sex-specific differences were found in the prevalences of a family history of diabetes, coronary heart disease, and hypertension (P > 0.05) in middle-aged population. Specific strategies to reduce modifiable risk factors for the prevention and control of diabetes and CVD may be warranted in this population. PMID:26406982

  7. 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…

  8. 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

  9. 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.

  10. Age- and Gender-Related Differences in LDL-Cholesterol Management in Outpatients with Type 2 Diabetes Mellitus

    PubMed Central

    Russo, Giuseppina; Pintaudi, Basilio; Giorda, Carlo; Lucisano, Giuseppe; Nicolucci, Antonio; Cristofaro, Maria Rosaria; Suraci, Concetta; Mulas, Maria Franca; Napoli, Angela; Rossi, Maria Chiara; Manicardi, Valeria

    2015-01-01

    Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD) risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein-cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem to reach LDL-C targets less frequently than men. Aim. To explore age- and gender-related differences in LDL-C management in a large sample of outpatients with T2DM. Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers in Italy were included. Women were older and more obese, with longer diabetes duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men (P < 0.0001). Lipid profile was monitored in ~75% of subjects, women being monitored less frequently than men, irrespective of age. More women did not reach the LDL-C target as compared to men, particularly in the subgroup treated with lipid-lowering medications. The between-genders gap in reaching LDL-C targets increased with age and diabetes duration, favouring men in all groups. Conclusions. LDL-C management is worst in women with T2DM, who are monitored and reach targets less frequently than T2DM men. Similarly to men, they do not receive medications despite high LDL-C. These gender discrepancies increase with age and diabetes duration, exposing older women to higher CHD risk. PMID:25873960

  11. Age- and Gender-Related Differences in LDL-Cholesterol Management in Outpatients with Type 2 Diabetes Mellitus.

    PubMed

    Russo, Giuseppina; Pintaudi, Basilio; Giorda, Carlo; Lucisano, Giuseppe; Nicolucci, Antonio; Cristofaro, Maria Rosaria; Suraci, Concetta; Mulas, Maria Franca; Napoli, Angela; Rossi, Maria Chiara; Manicardi, Valeria

    2015-01-01

    Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD) risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein-cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem to reach LDL-C targets less frequently than men. Aim. To explore age- and gender-related differences in LDL-C management in a large sample of outpatients with T2DM. Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers in Italy were included. Women were older and more obese, with longer diabetes duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men (P < 0.0001). Lipid profile was monitored in ~75% of subjects, women being monitored less frequently than men, irrespective of age. More women did not reach the LDL-C target as compared to men, particularly in the subgroup treated with lipid-lowering medications. The between-genders gap in reaching LDL-C targets increased with age and diabetes duration, favouring men in all groups. Conclusions. LDL-C management is worst in women with T2DM, who are monitored and reach targets less frequently than T2DM men. Similarly to men, they do not receive medications despite high LDL-C. These gender discrepancies increase with age and diabetes duration, exposing older women to higher CHD risk. PMID:25873960

  12. 5-HT obesity medication efficacy via POMC activation is maintained during aging.

    PubMed

    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; Heisler, Lora K

    2014-10-01

    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

  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. 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

  15. Peptides and Their Potential Role in the Treatment of Diabetes and Obesity

    PubMed Central

    Greenwood, Hannah C.; Bloom, Stephen R.; Murphy, Kevin G.

    2011-01-01

    It is estimated that 347 million people worldwide have diabetes and that over 1.5 billion adults worldwide are overweight. Predictions suggest these rates are increasing. Diabetes is a common complication in overweight and obese subjects, and in 2004, an estimated 3.4 million people died from consequences of high blood sugar. Thus, there is great interest in revealing the physiological systems that regulate body weight and blood sugar. Several peptidergic systems within the central nervous system and the periphery regulate energy homeostasis. A number of these systems have been investigated as potential treatments for obesity and the metabolic syndrome. However, manipulation of peptidergic systems poses many problems. This review discusses the peptidergic systems currently attracting research interest for their clinical potential to treat obesity. We consider first neuropeptides in the brain, including the orexigenic neuropeptide Y and melanin-concentrating hormone, and anorectic factors such as the melanocortins, ciliary neurotrophic factor, and neuromedin U. We subsequently discuss the utility of targeting peripheral gut peptides, including pancreatic polypeptide, peptide YY, amylin, and the gastric hormone ghrelin. Also, we analyze the evidence that these factors or drugs based on them may be therapeutically useful, while considering the disadvantages of using such peptides in a clinical context. PMID:22262073

  16. Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects.

    PubMed

    Emerenziani, Gian Pietro; Gallotta, Maria Chiara; Migliaccio, Silvia; Greco, Emanuela A; Marocco, Chiara; di Lazzaro, Luca; Fornari, Rachele; Lenzi, Andrea; Baldari, Carlo; Guidetti, Laura

    2016-01-01

    Aim of the study was to examine cardiorespiratory parameters at individual ventilatory threshold (IVT) and peak exercise capacity ([Formula: see text]) in outpatient diabetic and sarcopenic obese subjects. Seventeen obese subjects (BMI: 36.6 ± 4.1 kg·m(-1)) and sixteen SO subjects (BMI: 37.0 ± 7.3 kg·m(-1)) were compared with sixteen T2DM subjects (BMI: 37.7 ± 5.6 kg·m(-1)). All groups performed an incremental exercise test on a treadmill according to their physical ability. [Formula: see text], %HRmax, and maximal metabolic equivalent (METmax) were evaluated at maximal effort. Moreover, [Formula: see text], %[Formula: see text], %HRmax, %HRR, ΔHR, and METivt were assessed at IVT. No significant differences were found in any physiological parameters at maximal effort ([Formula: see text], %HRmax, and METmax) in all groups. On the contrary, [Formula: see text], %[Formula: see text], %HRmax, %HRR, ΔHR, and METivt were significantly lower in T2DM subjects as compared to OB and SO subjects at IVT (p < 0.05). Our results show that while at maximal effort there are no differences among groups, at IVT the physiological parameters are lower in T2DM subjects than in OB and SO subjects. Therefore, due to the differences observed in the groups, we suggest usng the IVT as a useful parameter to prescribe aerobic exercise in obese with sarcopenia or diabetes mellitus conditions. PMID:26884760

  17. 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

  18. Culturally adapting the prevention of diabetes and obesity in South Asians (PODOSA) trial.

    PubMed

    Wallia, S; Bhopal, R S; Douglas, A; Bhopal, R; Sharma, A; Hutchison, A; Murray, G; Gill, J; Sattar, N; Lawton, J; Tuomilehto, J; Mcknight, J; Forbes, J; Lean, M; Sheikh, A

    2014-12-01

    Type 2 diabetes is extremely common in South Asians, e.g. in men from Pakistani and Indian populations it is about three times as likely as in the general population in England, despite similarities in body mass index. Lifestyle interventions reduce the incidence of diabetes. Trials in Europe and North America have not, however, reported on the impact on South Asian populations separately or provided the details of their cross-cultural adaptation processes. Prevention of diabetes and obesity in South Asians (PODOSA) is a randomized, controlled trial in Scotland of an adapted, lifestyle intervention aimed at reducing weight and increasing physical activity to reduce type 2 diabetes in Indians and Pakistanis. The trial was adapted from the Finnish Diabetes Prevention Study. We describe, reflect on and discuss the following key issues: The core adaptations to the trial design, particularly the delivery of the intervention in homes by dietitians rather than in clinics. The use of both a multilingual panel and professional translators to help translate and/or develop materials. The processes and challenges of phonetic translation. How intervention resources were adapted, modified, newly developed and translated into Urdu and Gurmukhi (written Punjabi). The insights gained in PODOSA (including time pressures on investigators, imperfections in the adaptation process, the power of verbal rather than written information, the utilization of English and the mother-tongue languages simultaneously by participants and the costs) might help the research community, given the challenge of health promotion in multi-ethnic, urban societies. PMID:23574693

  19. 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

  20. 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

  1. Variance-component analysis of obesity in type 2 diabetes confirms loci on chromosomes 1q and 11q.

    PubMed

    van Tilburg, Jonathan H O; Sandkuijl, Lodewijk A; Strengman, Eric; Pearson, Peter L; van Haeften, Timon W; Wijmenga, Cisca

    2003-11-01

    To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome-wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of approximately 75% covering all 22 autosomes. Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores > or =1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine-mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. Our study to determine linkage for BMI confirms the presence of quantitative trait loci influencing obesity in subjects with type 2 diabetes on chromosomes 1q31-q42 and 11q14-q24. PMID:14627748

  2. [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

  3. 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. PMID:25538312

  4. 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

  5. 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

  6. Antiobesity effects of Kaempferia parviflora in spontaneously obese type II diabetic mice.

    PubMed

    Akase, Tomoko; Shimada, Tsutomu; Terabayashi, Susumu; Ikeya, Yukinobu; Sanada, Hiromi; Aburada, Masaki

    2011-01-01

    Kaempferia parviflora Wall. Ex Baker (KP) has been used as a folk medicine in Laos and Thailand to lower blood glucose levels, improve blood flow, and increase vitality. This study investigated the preventive effects of KP on obesity and its downstream symptoms (various metabolic disorders) using Tsumura, Suzuki, Obese Diabetes (TSOD) mice, a multifactorial genetic disease animal model in which metabolic diseases develop spontaneously, similar to metabolic syndrome in humans, and Tsumura, Suzuki, Non-Obesity (TSNO) mice as the corresponding control mice. When feed that was mixed with KP (1 or 3%) was given ad libitum to TSOD and TSNO mice for 8 weeks, body weight increase, visceral fat accumulation, lipid metabolism abnormalities, hyperinsulinemia, glucose intolerance, insulin resistance, hypertension, and peripheral neuropathy were suppressed in TSOD mice, but no marked differences were observed in TSNO mice. Because KP had preventive effects on metabolic diseases, including antiobesity effects, only in obese animals, we propose that KP will be extremely valuable as a medicine or component of food in alternative health care. PMID:20814753

  7. Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats.

    PubMed

    Scarpace, P J; Matheny, M; Zhang, Y; Tümer, N; Frase, C D; Shek, E W; Hong, B; Prima, V; Zolotukhin, S

    2002-03-01

    The purpose of this study was to determine if long-term leptin treatment desensitizes leptin signal transduction and the subsequent downstream anorexic and thermogenic responses in normal and leptin-resistant age-related obese rats. To this end, we administered, i.c.v., recombinant adeno-associated virus encoding rat leptin cDNA (rAAV-leptin) or control virus into young and aged-obese rats and after 9 or 46 days, examined food intake, oxygen consumption, body weight, serum leptin, STAT3 phosphorylation, hypothalamic NPY and POMC mRNAs, and UCP1 expression and protein level in brown adipose tissue (BAT). In young rats, rAAV-leptin depleted body fat and both anorexic and thermogenic mechanisms contributed to this effect. Moreover, leptin signal transduction was not desensitized, and there were persistent physiological responses. Similarly, in the aged-obese rats, there was unabated leptin signal transduction, however, both the anorexic and thermogenic responses completely attenuated sometime after day 9. This attenuation, downstream of the leptin receptor, may be contributing to the leptin-resistance and age-related weight gain in these aged-obese rats. Finally, in young rats, although the initial responses to rAAV-leptin were dominated by anorexic responses, by 46 days, the predominant response was thermogenic rather than anorexic, suggesting that energy expenditure may be an important component of long-term weight maintenance. PMID:11955525

  8. 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

  9. Alzheimer’s Disease And Type 2 Diabetes: Exploring The Association To Obesity And Tyrosine Hydroxylase

    PubMed Central

    Priyadarshini, Medha; Kamal, Mohammad A.; Greig, Nigel H.; Reale, Marcella; Abuzenadah, Adel M.; Chaudhary, Adeel G.A.; Damanhouri, Ghazi A.

    2016-01-01

    Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two debilitating health disorders afflicting millions worldwide. Recent research has revealed similarities between AD and T2DM. Both these protein conformational disorders are associated with obesity, insulin resistance, inflammation and endoplasmic reticulum stress, en-route initiation and/or stage aggravation. In this mini review we have tried to summarize studies describing obesity, insulin resistance and glucocorticoid imbalance as common patho-mechanisms in T2DM and AD. A reduction in tyrosine hydroxylase (TH) in the brain has been found to occur in Parkinson’s disease (PD). AD, T2DM and PD share common risk factors like depression. Thus, whether TH is involved in the ‘state of cognitive depression’ that is the hallmark of AD and often accompanies PD and T2DM is also explored. PMID:22583431

  10. 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

  11. Correlation of liver enzymes with diabetes and pre-diabetes in middle-aged rural population in China.

    PubMed

    Xie, Jun-hui; Liu, Qian; Yang, Yan; Liu, Zhe-long; Hu, Shu-hong; Zhou, Xin-rong; Yuan, Gang; Zhang, Mu-xun; Tao, Jing; Yu, Xue-feng

    2016-02-01

    The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus (T2DM) and pre-diabetes (pre-DM) in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test (OGTT) was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases (ALT and GGT), HbA1C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), impaired fasting glucose combined with impaired glucose tolerance (IFG+IGT) and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio (WHR), blood pressure, fasting blood glucose (FBG), high density lipoprotein-cholesterol (HDL-C), and liver enzymes (ALT and GGT). Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance (IR) in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders. PMID:26838740

  12. 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. PMID:27116186

  13. 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

  14. Endogenous ω-3 polyunsaturated fatty acid production confers resistance to obesity, dyslipidemia, and diabetes in mice.

    PubMed

    Li, Jie; Li, Fanghong R; Wei, Dong; Jia, Wei; Kang, Jing X; Stefanovic-Racic, Maja; Dai, Yifan; Zhao, Allan Z

    2014-08-01

    Despite the well-documented health benefits of ω-3 polyunsaturated fatty acids (PUFAs), their use in clinical management of hyperglycemia and obesity has shown little success. To better define the mechanisms of ω-3 PUFAs in regulating energy balance and insulin sensitivity, we deployed a transgenic mouse model capable of endogenously producing ω-3 PUFAs while reducing ω-6 PUFAs owing to the expression of a Caenorhabditis elegans fat-1 gene encoding an ω-3 fatty acid desaturase. When challenged with high-fat diets, fat-1 mice strongly resisted obesity, diabetes, hypercholesterolemia, and hepatic steatosis. Endogenous elevation of ω-3 PUFAs and reduction of ω-6 PUFAs did not alter the amount of food intake but led to increased energy expenditure in the fat-1 mice. The requirements for the levels of ω-3 PUFAs as well as the ω-6/ω-3 ratios in controlling blood glucose and obesity are much more stringent than those in lipid metabolism. These metabolic phenotypes were accompanied by attenuation of the inflammatory state because tissue levels of prostaglandin E2, leukotriene B4, monocyte chemoattractant protein-1, and TNF-α were significantly decreased. TNF-α-induced nuclear factor-κB signaling was almost completely abolished. Consistent with the reduction in chronic inflammation and a significant increase in peroxisome proliferator-activated receptor-γ activity in the fat-1 liver tissue, hepatic insulin signaling was sharply elevated. The activities of prolipogenic regulators, such as liver X receptor, stearoyl-CoA desaturase-1, and sterol regulatory element binding protein-1 were sharply decreased, whereas the activity of peroxisome proliferator-activated receptor-α, a nuclear receptor that facilitates lipid β-oxidation, was markedly increased. Thus, endogenous conversion of ω-6 to ω-3 PUFAs via fat-1 strongly protects against obesity, diabetes, inflammation, and dyslipidemia and may represent a novel therapeutic modality to treat these prevalent

  15. 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

  16. Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models

    PubMed Central

    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

  17. 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

  18. 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.

  19. 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.

  20. Vitamin D Insufficiency Is Associated with Abdominal Obesity in Urban Asian Indians Without Diabetes in North India

    PubMed Central

    Bhatt, Surya Prakash; Sharma, Mukti; Guleria, Randeep; Pandey, Ravindra Mohan; Luthra, Kalpana

    2014-01-01

    Abstract Objective: We evaluated the associations of serum 25-hydroxyvitamin D [25(OH) D] levels with clinical, biochemical, and anthropometric profiles and total abdominal adipose tissue (TAAT), subcutaneous abdominal adipose tissue (SCAT), and intraabdominal adipose tissue (IAAT) depots in Asian Indians without diabetes residing in north India. Subjects and Methods: In this cross-sectional study (n=137; 74 males and 63 females; 18–60 years of age), anthropometric (body mass index, waist and hip circumferences, and skinfold thickness at four sites) and biochemical (fasting plasma glucose, lipid profile, and fasting insulin levels) assessments were done. Measurement of percentage body fat was done by dual energy x-ray absorptiometry, and areas of TAAT, SCAT and IAAT were measured at the L2–L3 intervertebral level by single-slice magnetic resonance imaging. Levels of 25(OH) D were measured by radioimmunoassay. Correlation analysis was used to assess relationships among clinical, biochemical, and anthropometric profiles, areas of TAAT, SCAT, and IAAT, and 25(OH) D levels. Results: The mean concentration of 25(OH) D was 40.5±8.6 ng/mL. Overall, 6.6% had vitamin D deficiency (<10 ng/mL), 87.6% had insufficiency (<30 ng/mL), and 5.8% had a sufficient level (>30 ng/mL). Levels of 25(OH) D did not correlate with demographic, biochemical, and anthropometric profiles or with abdominal fat depots (TAAT, SCAT, and IAAT). In the correlation regression model, 25(OH) D was associated with TAAT in obese subjects. Conclusions: In obese urban Asian Indians without diabetes, higher values of total abdominal fat at the L2–L3 intervertebral level were associated with low 25(OH) D levels. PMID:24528222

  1. Inhibitory activities of Ulva lactuca polysaccharides on digestive enzymes related to diabetes and obesity.

    PubMed

    BelHadj, Sahla; Hentati, Olfa; Elfeki, Abdelfattah; Hamden, Khaled

    2013-05-01

    The aim of this study was to evaluate the effect of alga Ulva lactuca polysaccharides (ULPS) on key enzymes related to diabetes and obesity. This marine natural product, ULPS, exerted potential inhibition on key enzymes related to starch digestion and absorption in both plasma and small intestine mainly α-amylase by 53% and 34% and maltase by 97 and 164% respectively, leading to a significant decrease in blood glucose rate by 297%. Moreover, ULPS potentially inhibited key enzymes of lipid metabolism and absorption as lipase activity in both plasma and small intestine by 235 and 287% respectively, which led to a notable decrease of blood LDL-cholesterol and triglycerides levels, and in the counterpart an increase in HDL-cholesterol level in surviving diabetic rats. Additively, ULPS significantly protected the liver-kidney functions, by decreasing of aspartate transaminase (AST), alanine transaminase (ALT) and gamma-glytamyl transpeptidase (GGT) activities and creatinine, urea and albumin rates in plasma. PMID:23638862

  2. [GLP-1 receptor agonists versus SGLT-2 inhibitors in obese type 2 diabetes patients].

    PubMed

    Marques, Ana Rita Forte; Jaafar, Jaafar; de Kalbermatten, Bénédicte; Philippe, Jacques

    2015-06-01

    Who never had a type 2 obese diabetic patient, treated by several oral antidiabetic drugs and insulin, with consequent weight gain associated with the therapeutic escalation and uncontrolled diabetes? The arrival of GLP-1 agonists and SGLT-2 inhibitors allows to reevaluate the management of these patients, with their favorable effects on glycemic control, weight and the risk of hypoglycemia and their complementary mechanisms to conventional treatments. The vicious cycle of weight gain and increased need of insulin is limited. The choice between these two molecules must be based on several factors (glycemic target, weight, comorbidities, route of administration, side effects, etc.), and the balanced enthusiasm of these new treatments with the insufficient data regarding their long-term safety and their impact on micro- and macrovascular complications. PMID:26211282

  3. 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

  4. 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

  5. Histophysiology of the obesity-diabetes syndrome in sand rats.

    PubMed

    Hahn von Dorsche, H; Schäfer, H; Titlbach, M

    1994-01-01

    Insulin, glucagon, somatostatin, and PP cells were found by immunotopochemical and electron-optical techniques in the islets of Langerhans of the sand rat, proving that the islets in this species also contain the four basic cell types known to be found in the islets in mammals in general. The ratio of A cells to B cells was 1:4 (19.1% A cells to 80.9% B cells). The pancreas of the sand rat contained assemblages of various numbers of neurons in the intralobal and interlobular connective tissue. They did not seem related in any regular fashion to specific blood vessels or branches of the pancreatic ducts. No bundles of nerve fibers were found by either light or electron microscopy. Nonmyelinated nerve fibers were detected by electron microscopy in the stroma of the islets. In the sand rat the neuroinsular complexes are formed by the penetration of single nerve cells into the pancreatic islets. In the NH or long-term group the islets exhibited signs of stimulation. The number of islets was higher than normal (polynesia), with the islets themselves enlarged (macronesia). Double islets in the secretory ducts of the exocrine pancreas were frequent. The increase in islet size was due to hyperplasia of the B cells. The numbers of beta-granules in the B cells varied considerably. Glycogen was demonstrated in some islets. The fusion of beta-granules was shown in electron microscopic pictures. The electron-opaque centers of these granules were brighter than the others and appeared to have partly dissolved. The organelles of the B cells (ER, Golgi apparatus, and mitochondria) were well developed, this also being a sign of cell stimulation. No changes were observed in the B and PP cells. Stimulation of the islet cells was even more pronounced in the diabetic group. Due to hyperplasia, the islets in this group were significantly larger not only than those in the control group, but also than those in the NH group. The pancreata of this group of sand rats contained numerous small

  6. Aging and Physical Function in Type 2 Diabetes: 8 Years of an Intensive Lifestyle Intervention

    PubMed Central

    Bray, George A.; Chen, Shyh-Huei; Clark, Jeanne M.; Evans, Mary; Hill, James O.; Jakicic, John M.; Johnson, Karen C.; Neiberg, Rebecca; Ip, Edward H.

    2015-01-01

    Background. Compared with adults without type 2 diabetes mellitus, those with the disease experience more limitations in their physical functioning (PF). Look AHEAD is a large multicenter trial that examined the effects of an intensive lifestyle intervention (ILI) for weight loss on cardiovascular outcomes compared with diabetes support and education (DSE). Although the current study compared treatment differences between ILI and DSE on PF, the primary goal was to examine whether this effect was moderated by age and history of cardiovascular disease at enrollment. Methods. Overweight or obese adults with type 2 diabetes mellitus (n = 5,145) were randomly assigned to either ILI or DSE. The mean (±SD) age and % females in ILI was 58.9 years (±6.9) and 59.8%; it was 58.6 years (6.8) and 59.5% in DSE. Analysis in 4,998 participants assessed the differential rates of decline in PF across a period of 8 years for the ILI and DSE groups. Results. ILI resulted in improved PF compared with DSE after 1 year (p < .0001) and was maintained across time. Within the ILI, older adults experienced greater improvements than younger adults (p < .0001). By year 2, persons in ILI with preexisting cardiovascular disease were no different in PF than in DSE participants with preexisting cardiovascular disease. Conclusion. With the exception of persons who had a history of cardiovascular disease, ILI slowed the decline in PF with type 2 diabetes mellitus despite weight regain, an effect that was stronger for older than younger participants and could translate into reductions in falls and disability. PMID:24986062

  7. 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

  8. 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

  9. Obesity

    MedlinePlus

    Obesity means having too much body fat. It is different from being overweight, which means weighing too ... what's considered healthy for his or her height. Obesity occurs over time when you eat more calories ...

  10. 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. Subsequent adjustment for lifestyle factors modestly attenuated these associations. Of the 3 devices, ownership of a television had the strongest association with obesity (OR 1.39, 95% CI 1.29–1.49) and diabetes (OR 1.33, 95% CI 1.23–1.44). When stratified by country income level, the odds of obesity and diabetes when owning all 3 devices was greatest in low income countries (obesity: OR 3.15, 95% CI 2.33–4.25; diabetes: OR 1.97, 95% CI 1.53–2.53) and decreased through country income levels such that we did not detect an association in high income countries. Interpretation: The ownership of household devices increased the likelihood of obesity and diabetes, and this was mediated in part by effects on physical

  11. Exercise training improves hemodynamic recovery to isometric exercise in obese men with type 2 diabetes but not in obese women

    PubMed Central

    Kanaley, Jill A.; Goulopoulou, Styliani; Franklin, Ruth; Baynard, Tracy; Carhart, Robert L; Weinstock, Ruth S; Fernhall, Bo

    2012-01-01

    Objectives Women with type 2 diabetes (T2D) show greater rates of mortality due to ischemic heart disease than men with T2D. We aimed to examine cardiovascular and autonomic function responses to isometric handgrip (IHG) exercise between men and women with T2D, before and after an exercise training program. Materials/Methods Hemodynamic responses were measured in 22 men and women with T2D during and following a 3-minute IHG test, and before and after 16 wks of aerobic exercise training. Results Women had a smaller decrease in mean arterial pressure (MAP) and systolic blood pressure (BP) during recovery from IHG (ΔMAPREC) than men pre- and post-training (P<0.05). Men showed a greater reduction in diastolic BP during recovery from IHG (P<0.05), and exercise training improved this response in men but not in women (men, pre-training: −13.9±1.8, post-training: −20.5±5.3 mmHg vs. women, pre-training: −10.7±1.7, post-training: −4.1±4.9 mmHg; P<0.05). Men had a greater reduction in sympathetic modulation of vasomotor tone (P<0.05), as estimated by blood pressure variability, following IHG. This response was accentuated after training, while this training effect was not seen in women. Post-training ΔMAPREC was correlated with recovery of low frequency component of the BP spectrum (ΔLFSBPrec, r=0.52, P<0.05). Conclusions Differences in BP recovery immediately following IHG may be attributed to gender differences in cardiovascular autonomic modulation. An improvement in these responses occurs following aerobic exercise training in obese men, but not in obese women with T2D which reflects a better adaptive autonomic response to exercise training. PMID:22902004

  12. Maternal Glucose and Fatty Acid Kinetics and Infant Birth Weight in Obese Women With Type 2 Diabetes.

    PubMed

    Cade, W Todd; Tinius, Rachel A; Reeds, Dominic N; Patterson, Bruce W; Cahill, Alison G

    2016-04-01

    The objectives of this study were 1) to describe maternal glucose and lipid kinetics and 2) to examine the relationships with infant birth weight in obese women with pregestational type 2 diabetes during late pregnancy. Using stable isotope tracer methodology and mass spectrometry, maternal glucose and lipid kinetic rates during the basal condition were compared in three groups: lean women without diabetes (Lean, n = 25), obese women without diabetes (OB, n = 26), and obese women with pregestational type 2 diabetes (OB+DM, n = 28; total n = 79). Glucose and lipid kinetics during hyperinsulinemia were also measured in a subset of participants (n = 56). Relationships between maternal glucose and lipid kinetics during both conditions and infant birth weight were examined. Maternal endogenous glucose production (EGP) rate was higher in OB+DM than OB and Lean during hyperinsulinemia. Maternal insulin value at 50% palmitate Ra suppression (IC50) for palmitate suppression with insulinemia was higher in OB+DM than OB and Lean. Maternal EGP per unit insulin and plasma free fatty acid concentration during hyperinsulinemia most strongly predicted infant birth weight. Our findings suggest maternal fatty acid and glucose kinetics are altered during late pregnancy and might suggest a mechanism for higher birth weight in obese women with pregestational diabetes. PMID:26861786

  13. Short-lived diabetes in the young-adult ZDF rat does not exacerbate neuronal Ca(2+) biomarkers of aging.

    PubMed

    Maimaiti, Shaniya; DeMoll, Chris; Anderson, Katie L; Griggs, Ryan B; Taylor, Bradley K; Porter, Nada M; Thibault, Olivier

    2015-09-24

    Results from clinical studies provide evidence that cognitive changes relatively late in life may be traced to antecedent conditions including diabetes, obesity, a sedentary lifestyle, and an atherogenic diet. As such, several traits of Type 2 diabetes (T2DM) could be considered pathogenic factors of aging, contributing to age-dependent cognitive decline and our susceptibility to Alzheimer's disease. It appears that both the duration of metabolic condition and the age of the individual, together can contribute to the potential impact on peripheral as well as brain health. Because of robust evidence that in animal models of aging, Ca(2+) dysregulation alters neuronal health, synaptic plasticity, and learning and memory processes, we tested the hypothesis that peripheral metabolic dysregulation could exacerbate Ca(2+) dysfunction in hippocampal CA1 neurons. Using intracellular/ extracellular electrophysiological and Ca(2+) imaging techniques, we show that Ca(2+)levels at rest or during synaptic stimulation, the Ca(2+)-dependent afterhyperpolarization, baseline field potentials, and short-term synaptic plasticity were not significantly altered in young-adult male Zucker diabetic fatty rats compare to their lean counterparts. Our observations suggest that early phases of T2DM characterized by high levels of glucose and insulin may be too transient to alter hippocampal CA1 physiology in this animal model of diabetes. These results are supported by clinical data showing that longer T2DM duration can have greater negative impact on cognitive functions. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25451110

  14. An acute bout of whole body passive hyperthermia increases plasma leptin, but does not alter glucose or insulin responses in obese type 2 diabetics and healthy adults.

    PubMed

    Rivas, Eric; Newmire, Dan E; Crandall, Craig G; Hooper, Philip L; Ben-Ezra, Vic

    2016-07-01

    Acute and chronic hyperthermic treatments in diabetic animal models repeatedly improve insulin sensitivity and glycemic control. Therefore, the purpose of this study was to test the hypothesis that an acute 1h bout of hyperthermic treatment improves glucose, insulin, and leptin responses to an oral glucose challenge (OGTT) in obese type 2 diabetics and healthy humans. Nine obese (45±7.1% fat mass) type 2 diabetics (T2DM: 50.1±12y, 7.5±1.8% HbA1c) absent of insulin therapy and nine similar aged (41.1±13.7y) healthy non-obese controls (HC: 33.4±7.8% fat mass, P<0.01; 5.3±0.4% HbA1c, P<0.01) participated. Using a randomized design, subjects underwent either a whole body passive hyperthermia treatment via head-out hot water immersion (1h resting in 39.4±0.4°C water) that increased internal temperature above baseline by ∆1.6±0.4°C or a control resting condition. Twenty-four hours post treatments, a 75g OGTT was administered to evaluate changes in plasma glucose, insulin, C-peptide, and leptin concentrations. Hyperthermia itself did not alter area under the curve for plasma glucose, insulin, or C-peptide during the OGTT in either group. Fasting absolute and normalized (kg·fat mass) plasma leptin was significantly increased (P<0.01) only after the hyperthermic exposure by 17% in T2DM and 24% in HC groups (P<0.001) when compared to the control condition. These data indicate that an acute hyperthermic treatment does not improve glucose tolerance 24h post treatment in moderate metabolic controlled obese T2DM or HC individuals. PMID:27264884

  15. [DYNAMICS OF METABOLIC CHARACTERISTICS, MARKERS OF OXIDATIVE STRESS AND VASCULAR WALL DAMAGE DURING TREATMENT OF OBESE PRE-DIABETIC PATIENTS].

    PubMed

    Romanenko, L A; Polyatykina T S; Mavrycheva, N V; Budnikova, N V; Grinshtein, V B

    2016-01-01

    We studied lipid and carbohydrate metabolism, markers of oxidative stress (plasma malonic dialdehyde and dienoic conjugates) and vascular wall damage (CRP microalbuminuria, blood desquamated endotheliocytes) before and after 12 week treatment of obese pre-diabetic patients. The study showed positive dynamics of the above metabolic parameters with normalization of carbohydrate metabolism in 60% of the patients and angioprotective effect of prescribed therapy. The proposed treatment can be used to prevent diabetes mellitus. PMID:27522729

  16. Recruitment into diabetes prevention programs: what is the impact of errors in self-reported measures of obesity?

    PubMed Central

    2012-01-01

    Background Error in self-reported measures of obesity has been frequently described, but the effect of self-reported error on recruitment into diabetes prevention programs is not well established. The aim of this study was to examine the effect of using self-reported obesity data from the Finnish diabetes risk score (FINDRISC) on recruitment into the Greater Green Triangle Diabetes Prevention Project (GGT DPP). Methods The GGT DPP was a structured group-based lifestyle modification program delivered in primary health care settings in South-Eastern Australia. Between 2004–05, 850 FINDRISC forms were collected during recruitment for the GGT DPP. Eligible individuals, at moderate to high risk of developing diabetes, were invited to undertake baseline tests, including anthropometric measurements performed by specially trained nurses. In addition to errors in calculating total risk scores, accuracy of self-reported data (height, weight, waist circumference (WC) and Body Mass Index (BMI)) from FINDRISCs was compared with baseline data, with impact on participation eligibility presented. Results Overall, calculation errors impacted on eligibility in 18 cases (2.1%). Of n = 279 GGT DPP participants with measured data, errors (total score calculation, BMI or WC) in self-report were found in n = 90 (32.3%). These errors were equally likely to result in under- or over-reported risk. Under-reporting was more common in those reporting lower risk scores (Spearman-rho = −0.226, p-value < 0.001). However, underestimation resulted in only 6% of individuals at high risk of diabetes being incorrectly categorised as moderate or low risk of diabetes. Conclusions Overall FINDRISC was found to be an effective tool to screen and recruit participants at moderate to high risk of diabetes, accurately categorising levels of overweight and obesity using self-report data. The results could be generalisable to other diabetes prevention programs using screening tools which

  17. Effect change of obesity on diabetes depending on measurement: self-reported body mas index from 2012 Community Health Survey vs. directly measured from the Korea National Health and Nutrition Examination Survey

    PubMed Central

    Yoon, Kyuhyun; Min, Kyungduk; Chun, Heeran; Jang, Soong-Nang; Cho, Sung-il

    2015-01-01

    OBJECTIVES: Obesity is a well-recognized risk factor for type 2 diabetes mellitus (DM) among young and middle-aged adults in South Korea. To elaborate on the association between obesity and Diabetes mellitus (DM), subjective data from self-reporting survey or objective data from health examination is generally used. This study was conducted to validate the change of association from using these different measurements. METHODS: Community Health Survey data and Korea National Health and Nutrition Examination Survey data, as subjective and objective data respectively, were used. Population, resident in Seoul and over 45 aged, were selected for the study and the association between obesity and DM were defined by using multivariate logistic regression model. RESULTS: In subjective data, DM prevalence was 12.4% (male, 14.7; female, 10.6) and obesity prevalence was 26.0% (male, 29.2; female, 23.4). Whereas, in objective data, DM prevalence was 15.0% (male, 17.8; female, 12.9), and obese population was 32.4% (male, 34.4; female, 30.8). Based on the effect of obesity on DM prevalence from each data, using objective data increased the impact of obesity. Difference of relative risk of obesity between from subjective data and from objective was bigger in female than male and statistically significant. CONCLUSIONS: The differences of association pattern between subjective and objective data were found, due to higher obesity prevalence in objective data, and discrepancies of socio-economic status. These discrepancies could be inevitable Therefore we have to face them proactively, and understand the different aspect of various variables from different measurement. PMID:25666235

  18. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  19. Obesity and Cognitive Dysfunction in Heart Failure: The Role of Hypertension, Type 2 Diabetes, and Physical Fitness

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Background Cognitive impairment is common in heart failure (HF). Obesity is a known risk factor for cognitive dysfunction in HF, though the mechanisms remain unclear. Obesity increases risk for conditions like hypertension and type 2 diabetes mellitus (T2DM), as well as poor fitness levels and this may serve as one possible pathway accounting for association between obesity and cognitive dysfunction. Aims We used structural equation modeling (SEM) to test whether the combination of hypertension, T2DM, and reduced fitness mediate the association between obesity and cognitive dysfunction. Methods 200 HF patients completed neuropsychological testing and a physical fitness assessment. Hypertension and T2DM were ascertained via self-report and medical records. Body mass index (BMI) was calculated. Results 43% of the sample was obese. Hypertension (70%) and T2DM (36%) were common, and fitness levels were reduced. The SEM model with these factors as mediators between BMI and cognitive function demonstrated excellent fit (CFI = 0.98; RMSEA = .03). Higher BMI correlated with hypertension, T2DM, and poorer fitness. Each of these factors predicted worse cognition. Models that isolated medical comorbidities and physical fitness as the mediator were weaker than the full model. Conclusions Increased risk for medical comorbidities and reduced fitness levels helped to explain the negative effects of obesity on cognitive dysfunction in HF. Prospective studies should confirm this pattern and examine weight loss benefits cognitive function in HF. Keywords: Physical fitness; cognitive function; heart failure; obesity; hypertension; type 2 diabetes mellitus PMID:24829294

  20. SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus

    PubMed Central

    Hassing, H. Carlijne; Surendran, R. Preethi; Derudas, Bruno; Verrijken, An; Francque, Sven M.; Mooij, Hans L.; Bernelot Moens, Sophie J.; ’t Hart, Leen M.; Nijpels, Giel; Dekker, Jacqueline M.; Williams, Kevin Jon; Stroes, Erik S. G.; Van Gaal, Luc F.; Staels, Bart; Nieuwdorp, Max; Dallinga-Thie, Geesje M.

    2014-01-01

    Objective Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodelling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here we sought to investigate the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM. Design and Methods Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Results Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; p=0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (p<0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P<0.05) and retinyl esters (RE) levels (P<0.001). Conclusions These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM. PMID:24339435

  1. Ethnicity-specific obesity cut-points in the development of Type 2 diabetes – a prospective study including three ethnic groups in the United Kingdom

    PubMed Central

    Tillin, T; Sattar, N; Godsland, I F; Hughes, A D; Chaturvedi, N; Forouhi, N G

    2015-01-01

    Aims Conventional definitions of obesity, e.g. body mass index (BMI) ≥ 30 kg/m2 or waist circumference cut-points of 102 cm (men) and 88 cm (women), may underestimate metabolic risk in non-Europeans. We prospectively identified equivalent ethnicity-specific obesity cut-points for the estimation of diabetes risk in British South Asians, African-Caribbeans and Europeans. Methods We studied a population-based cohort from London, UK (1356 Europeans, 842 South Asians, 335 African-Caribbeans) who were aged 40–69 years at baseline (1988–1991), when they underwent anthropometry, fasting and post-load (75 g oral glucose tolerance test) blood tests. Incident Type 2 diabetes was identified from primary care records, participant recall and/or follow-up biochemistry. Ethnicity-specific obesity cut-points in association with diabetes incidence were estimated using negative binomial regression. Results Diabetes incidence rates (per 1000 person years) at a median follow-up of 19 years were 20.8 (95% CI: 18.4, 23.6) and 12.0 (8.3, 17.2) in South Asian men and women, 16.5 (12.7, 21.4) and 17.5 (13.0, 23.7) in African-Caribbean men and women, and 7.4 (6.3, 8.7), and 7.2 (5.3, 9.8) in European men and women. For incidence rates equivalent to those at a BMI of 30 kg/m2 in European men and women, age- and sex-adjusted cut-points were: South Asians, 25.2 (23.4, 26.6) kg/m2; and African-Caribbeans, 27.2 (25.2, 28.6) kg/m2. For South Asian and African-Caribbean men, respectively, waist circumference cut-points of 90.4 (85.0, 94.5) and 90.6 (85.0, 94.5) cm were equivalent to a value of 102 cm in European men. Waist circumference cut-points of 84.0 (74.0, 90.0) cm in South Asian women and 81.2 (71.4, 87.4) cm in African-Caribbean women were equivalent to a value of 88 cm in European women. Conclusions In prospective analyses, British South Asians and African-Caribbeans had equivalent diabetes incidence rates at substantially lower obesity levels than the conventional European cut

  2. Circulating serum irisin levels in obesity and type 2 diabetes mellitus.

    PubMed

    Shoukry, Amira; Shalaby, Sally M; El-Arabi Bdeer, Shereen; Mahmoud, Amira A; Mousa, Mayada M; Khalifa, Ashraf

    2016-07-01

    Irisin is an exercise-regulated myokine inducing browning of white adipose tissue and has gained interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes mellitus (T2DM). The aim of this study is to evaluate the circulating serum irisin levels in obesity and T2DM and also to elucidate possible relationships between serum irisin levels with anthropometric and metabolic parameters of obesity and T2DM. One hundred fifty newly diagnosed T2DM patients as well as 150 nondiabetic control subjects were enrolled in this study. Nondiabetic controls were then stratified according to their body mass index (BMI) into three subgroups; lean, overweight, and obese. Serum irisin levels were evaluated by enzyme-linked immunosorbent assay. Serum irisin levels were significantly decreased in T2DM patients compared with nondiabetic controls. Obese nondiabetic controls had significantly higher serum irisin levels compared with lean nondiabetic controls. In both nondiabetic controls and T2DM patients, serum irisin was significantly positively correlated with BMI (r = 0.985, P < 0.001 and r = 0.218, P = 0.007, respectively), fat mass (r = 0.959, P < 0.001 and r = 0.202, P = 0.013, respectively), fat-free mass (r = 0.606, P < 0.001 and r = 0.194, P = 0.017, respectively), fat-free mass index (r = 0.820, P < 0.001 and r = 0.179, P = 0.028, respectively), waist-to-hip ratio (r = 0.880, P < 0.001 and r = 0.194, P = 0.017, respectively), fasting insulin (r = 0.989, P < 0.001 and r = 0.207, P = 0.011, respectively), and HOMA-IR (r = 0.989, P < 0.001 and r = 0.185, P = 0.023, respectively), whereas; significantly negatively correlated with insulin sensitivity (r = -0.992, P < 0.001 and r = -0.187, P = 0.022, respectively). In this study, we demonstrated that circulating serum irisin levels were increased in obese nondiabetic subjects, while decreased in T2DM patients. Moreover, serum irisin levels were correlated

  3. Diabetes and obesity treatment based on dual incretin receptor activation: 'twincretins'.

    PubMed

    Skow, M A; Bergmann, N C; Knop, F K

    2016-09-01

    The gut incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted after meal ingestion and work in concert to promote postprandial insulin secretion and regulate glucagon secretion. GLP-1 also slows gastric emptying and suppresses appetite, whereas GIP seems to affect lipid metabolism. The introduction of selective GLP-1 receptor (GLP-1R) agonists for the treatment of type 2 diabetes and obesity has increased the scientific and clinical interest in incretins. Combining the body weight-lowering and glucose-lowering effects of GLP-1 with a more potent improvement of β cell function through additional GIP action could potentially offer a more effective treatment of diabetes and obesity, with fewer adverse effects than selective GLP-1R agonists; therefore, new drugs designed to co-activate both the GIP receptor (GIPR) and the GLP-1R simultaneously are under development. In the present review, we address advances in the field of GIPR and GLP-1R co-agonism and review in vitro studies, animal studies and human trials involving co-administration of the two incretins, as well as results from a recently developed GIPR/GLP-1R co-agonist, and highlight promising areas and challenges within the field of incretin dual agonists. PMID:27160961

  4. Nutrition Education in an Era of Global Obesity and Diabetes: Thinking Outside the Box.

    PubMed

    Eisenberg, David M; Burgess, Jonathan D

    2015-07-01

    In an era when rates of obesity, diabetes, and other lifestyle-related diseases challenge medical educators and governments worldwide, it is necessary to consider novel educational strategies, both didactic and experiential, whereby current and future health professionals can be better prepared to proactively advise and teach patients enhanced self-care skills (e.g., diet, movement, stress management, and enhanced behavioral change).In this Perspective, the authors summarize current circumstances involving rising rates of obesity and diabetes worldwide, the lack of nutrition- and lifestyle-related curricular requirements for professional medical certification, societal trends regarding modern food culture and food availability in health care settings, and the misalignment of financial incentives to promote health.The authors assess what elements of self-care should or should not be required within future curricula and certification exams. They consider how best to educate trainees about diet and how to "translate" nutrition, exercise, and behavioral science knowledge into practical advice. They explore several ideas for reforming nutrition education, including "teaching kitchens" as required laboratory classes for nutrition and lifestyle instruction, wearable technologies for tracking behaviors and physiological data relating to lifestyle choices, and the prospect of hospitals and other medical venues serving as exemplars of healthy, delicious food options. Finally, the authors argue that "salutogenesis"-the study of the creation and maintenance of health and well-being-should assume its rightful position alongside the study of "pathogenesis"-disease diagnosis and treatment-in medical education and practice. PMID:25785680

  5. MR-Based Assessment of Bone Marrow Fat in Osteoporosis, Diabetes, and Obesity

    PubMed Central

    Cordes, Christian; Baum, Thomas; Dieckmeyer, Michael; Ruschke, Stefan; Diefenbach, Maximilian N.; Hauner, Hans; Kirschke, Jan S.; Karampinos, Dimitrios C.

    2016-01-01

    Bone consists of the mineralized component (i.e., cortex and trabeculae) and the non-mineralized component (i.e., bone marrow). Most of the routine clinical bone imaging uses X-ray-based techniques and focuses on the mineralized component. However, bone marrow adiposity has been also shown to have a strong linkage with bone health. Specifically, multiple previous studies have demonstrated a negative association between bone marrow fat fraction (BMFF) and bone mineral density. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are ideal imaging techniques for non-invasively investigating the properties of bone marrow fat. In the present work, we first review the most important MRI and MRS methods for assessing properties of bone marrow fat, including methodologies for measuring BMFF and bone marrow fatty acid composition parameters. Previous MRI and MRS studies measuring BMFF and fat unsaturation in the context of osteoporosis are then reviewed. Finally, previous studies investigating the relationship between bone marrow fat, other fat depots, and bone health in patients with obesity and type 2 diabetes are presented. In summary, MRI and MRS are powerful non-invasive techniques for measuring properties of bone marrow fat in osteoporosis, obesity, and type 2 diabetes and can assist in future studies investigating the pathophysiology of bone changes in the above clinical scenarios. PMID:27445977

  6. Environmental Influences on Development of Type 2 Diabetes and Obesity: Challenges in Personalizing Prevention and Management

    PubMed Central

    Ershow, Abby G.

    2009-01-01

    Recent epidemic increases in the U.S. prevalence of obesity and diabetes are a consequence of widespread environmental changes affecting energy balance and its regulation. These environmental changes range from exposure to endocrine disrupting pollutants to shortened sleep duration to physical inactivity to excess caloric intake. Overall, we need a better understanding of the factors affecting individual susceptibility and resistance to adverse exposures and behaviors and of determinants of individual response to treatment. Obesity and diabetes prevention will require responding to two primary behavioral risk factors: excess energy intake and insufficient energy expenditure. Adverse food environments (external, nonphysiological influences on eating behaviors) contribute to excess caloric intake but can be countered through behavioral and economic approaches. Adverse built environments, which can be modified to foster more physical activity, are promising venues for community-level intervention. Techniques to help people to modulate energy intake and increase energy expenditure must address their personal situations: health literacy, psychological factors, and social relationships. Behaviorally oriented translational research can help in developing useful interventions and environmental modifications that are tailored to individual needs. PMID:20144320

  7. Recent Progress in Anti-Obesity and Anti-Diabetes Effect of Berries

    PubMed Central

    Tsuda, Takanori

    2016-01-01

    Berries are rich in polyphenols such as anthocyanins. Various favorable functions of berries cannot be explained by their anti-oxidant properties, and thus, berries are now receiving great interest as food ingredients with “beyond antioxidant” functions. In this review, we discuss the potential health benefits of anthocyanin-rich berries, with a focus on prevention and treatment of obesity and diabetes. To better understand the physiological functionality of berries, the exact molecular mechanism of their anti-obesity and anti-diabetes effect should be clarified. Additionally, the relationship of metabolites and degradation products with health benefits derived from anthocyanins needs to be elucidated. The preventive effects of berries and anthocyanin-containing foods on the metabolic syndrome are not always supported by findings of interventional studies in humans, and thus further studies are necessary. Use of standardized diets and conditions by all research groups may address this problem. Berries are tasty foods that are easy to consume, and thus, investigating their health benefits is critical for health promotion and disease prevention. PMID:27058561

  8. Bisphenol A, Obesity, and Type 2 Diabetes Mellitus: Genuine Concern or Unnecessary Preoccupation?

    PubMed Central

    Mirmira, Priyadarshini; Evans-Molina, Carmella

    2014-01-01

    Bisphenol A or BPA is a ubiquitious industrial chemical found in a variety of plastic containers intended for food storage and in the epoxy resin linings of metal food and beverage cans, where it is used to prevent corrosion, food contamination, and spoilage. BPA has been recently linked to a wide variety of medical disorders and is known to have estrogenic activity with genomic as well as non-genomic estrogen-receptor mediated effects. Given rapidly increasing prevalence rates of metabolic disorders like obesity and Type 2 diabetes, BPA has recently come under intense scrutiny in scientific and lay communities as a potential endocrine disrupting compound with diabetogenic effects. The purpose of this review is to critically examine available literature investigating the link between BPA and alterations in metabolic health. Here, we discuss typical levels of exposure to BPA in daily life and analyze both epidemiological human data and mechanistic preclinical studies that have tested associations between BPA and obesity and diabetes. Finally, we summarize the current policies and views of national and international regulatory agencies regarding the safety of BPA use. PMID:24686036

  9. Added sugars and risk factors for obesity, diabetes and heart disease.

    PubMed

    Rippe, J M; Angelopoulos, T J

    2016-03-01

    The effects of added sugars on various chronic conditions are highly controversial. Some investigators have argued that added sugars increase the risk of obesity, diabetes and cardiovascular disease. However, few randomized controlled trials are available to support these assertions. The literature is further complicated by animal studies, as well as studies which compare pure fructose to pure glucose (neither of which is consumed to any appreciable degree in the human diet) and studies where large doses of added sugars beyond normal levels of human consumption have been administered. Various scientific and public health organizations have offered disparate recommendations for upper limits of added sugar. In this article, we will review recent randomized controlled trials and prospective cohort studies. We conclude that the normal added sugars in the human diet (for example, sucrose, high-fructose corn syrup and isoglucose) when consumed within the normal range of normal human consumption or substituted isoenergetically for other carbohydrates, do not appear to cause a unique risk of obesity, diabetes or cardiovascular disease. PMID:27001643

  10. Recent Progress in Anti-Obesity and Anti-Diabetes Effect of Berries.

    PubMed

    Tsuda, Takanori

    2016-01-01

    Berries are rich in polyphenols such as anthocyanins. Various favorable functions of berries cannot be explained by their anti-oxidant properties, and thus, berries are now receiving great interest as food ingredients with "beyond antioxidant" functions. In this review, we discuss the potential health benefits of anthocyanin-rich berries, with a focus on prevention and treatment of obesity and diabetes. To better understand the physiological functionality of berries, the exact molecular mechanism of their anti-obesity and anti-diabetes effect should be clarified. Additionally, the relationship of metabolites and degradation products with health benefits derived from anthocyanins needs to be elucidated. The preventive effects of berries and anthocyanin-containing foods on the metabolic syndrome are not always supported by findings of interventional studies in humans, and thus further studies are necessary. Use of standardized diets and conditions by all research groups may address this problem. Berries are tasty foods that are easy to consume, and thus, investigating their health benefits is critical for health promotion and disease prevention. PMID:27058561

  11. Fructose Metabolism and Relation to Atherosclerosis, Type 2 Diabetes, and Obesity

    PubMed Central

    Kolderup, Astrid; Svihus, Birger

    2015-01-01

    A high intake of sugars has been linked to diet-induced health problems. The fructose content in sugars consumed may also affect health, although the extent to which fructose has a particularly significant negative impact on health remains controversial. The aim of this narrative review is to describe the body's fructose management and to discuss the role of fructose as a risk factor for atherosclerosis, type 2 diabetes, and obesity. Despite some positive effects of fructose, such as high relative sweetness, high thermogenic effect, and low glycaemic index, a high intake of fructose, particularly when combined with glucose, can, to a larger extent than a similar glucose intake, lead to metabolic changes in the liver. Increased de novo lipogenesis (DNL), and thus altered blood lipid profile, seems to be the most prominent change. More studies with realistic consumption levels of fructose are needed, but current literature does not indicate that a normal consumption of fructose (approximately 50–60 g/day) increases the risk of atherosclerosis, type 2 diabetes, or obesity more than consumption of other sugars. However, a high intake of fructose, particularly if combined with a high energy intake in the form of glucose/starch, may have negative health effects via DNL. PMID:26199742

  12. Intermittent administration of brain-derived neurotrophic factor ameliorates glucose metabolism in obese diabetic mice.

    PubMed

    Ono, M; Itakura, Y; Nonomura, T; Nakagawa, T; Nakayama, C; Taiji, M; Noguchi, H

    2000-01-01

    We have previously shown that brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, interacts with the endocrine system in obese diabetic mice, and systemic peripheral administration of BDNF regulates glucose metabolism in this model. Results from the present study show that the hypoglycemic effect induced by 2 weeks' daily administration of BDNF (20 mg/kg/d) to db/db mice lasts for several weeks after treatment cessation, irrespective of food reduction. On the other hand, the antidiabetic agent, metformin had no lasting effect. This duration of the BDNF hypoglycemic action prompted us to examine the efficacy of BDNF intermittent administration on glucose metabolism. BDNF administered once or twice per week (70 mg/kg/wk) to db/db mice for 3 weeks significantly reduced blood glucose concentrations and hemoglobin A(1c), (HbA(1c)) as compared with ad libitum-fed phosphate-buffered saline (PBS)-treated and pair-fed PBS-treated groups. This suggests that BDNF not only temporarily reduced blood glucose concentrations but also ameliorated systemic glucose balance in this obese diabetic mouse model during the experimental period. Our results indicate that BDNF could be a novel hypoglycemic agent with an exceptional ability to normalize glucose metabolism even with treatment as infrequently as once per week. PMID:10647076

  13. Phosphatidylinositol-3,4,5-Triphosphate and Cellular Signaling: Implications for Obesity and Diabetes

    PubMed Central

    Manna, Prasenjit; Jain, Sushil K.

    2015-01-01

    Phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) is one of the most important phosphoinositides and is capable of activating a wide range of proteins through its interaction with their specific binding domains. Localization and activation of these effector proteins regulate a number of cellular functions, including cell survival, proliferation, cytoskeletal rearrangement, intracellular vesicle trafficking, and cell metabolism. Phosphoinositides have been investigated as an important agonist-dependent second messenger in the regulation of diverse physiological events depending upon the phosphorylation status of their inositol group. Dysregulation in formation as well as metabolism of phosphoinositides is associated with various pathophysiological disorders such as inflammation, allergy, cardiovascular diseases, cancer, and metabolic diseases. Recent studies have demonstrated that the impaired metabolism of PtdIns(3,4,5)P3 is a prime mediator of insulin resistance associated with various metabolic diseases including obesity and diabetes. This review examines the current status of the role of PtdIns(3,4,5)P3 signaling in the regulation of various cellular functions and the implications of dysregulated PtdIns(3,4,5)P3 signaling in obesity, diabetes, and their associated complications. PMID:25721445

  14. A High Level of Intestinal Alkaline Phosphatase Is Protective Against Type 2 Diabetes Mellitus Irrespective of Obesity.

    PubMed

    Malo, Madhu S

    2015-12-01

    Mice deficient in intestinal alkaline phosphatase (IAP) develop type 2 diabetes mellitus (T2DM). We hypothesized that a high level of IAP might be protective against T2DM in humans. We determined IAP levels in the stools of 202 diabetic patients and 445 healthy non-diabetic control people. We found that compared to controls, T2DM patients have approx. 50% less IAP (mean +/- SEM: 67.4 +/- 3.2 vs 35.3 +/- 2.5 U/g stool, respectively; p < 0.000001) indicating a protective role of IAP against T2DM. Multiple logistic regression analyses showed an independent association between the IAP level and diabetes status. With each 25 U/g decrease in stool IAP, there is a 35% increased risk of diabetes. The study revealed that obese people with high IAP (approx. 65 U/g stool) do not develop T2DM. Approx. 65% of the healthy population have < 65.0 U/g stool IAP, and predictably, these people might have 'the incipient metabolic syndrome', including 'incipient diabetes', and might develop T2DM and other metabolic disorders in the near future. In conclusion, high IAP levels appear to be protective against diabetes irrespective of obesity, and a 'temporal IAP profile' might be a valuable tool for predicting 'the incipient metabolic syndrome', including 'incipient diabetes'. PMID:26844282

  15. Evolution of obesity prevalence in France: an age-period-cohort analysis

    PubMed Central

    Diouf, Ibrahima; Charles, Marie Aline; Ducimetière, Pierre; Basdevant, Arnaud; Eschwege, Evelyne; Heude, Barbara

    2010-01-01

    Background A rapid increase in the prevalence of obesity has been reported in France since 1990. We investigated the impact of birth cohort on the changes in obesity prevalence after taking into account age and survey period. Methods We analyzed data from four national surveys in 1997, 2000, 2003 and 2006. For each survey, self-reported data on weight and height were recorded on mailed questionnaires sent to a sample of 20 000 households, representative of the French population. Obesity was defined according to WHO criteria, BMI ≥ 30 kg/m2. We modeled the prevalence of obesity using logistic regression with age, cohort and period as explanatory variables. As these variables are linearly dependent, only nonlinear effects can be estimated uniquely and interpreted, after including specific chosen constraints in the models. Results There was a progressive increase in the prevalence of obesity between 1997 and 2006, attributable either to a period or to a cohort effect. There was a substantial departure from a linear trend for the cohort effect only, which appeared to be stronger in women: there was an acceleration in the prevalence of obesity with birth cohort for individuals born after the mid-1960s, in both sexes. Conclusions Our results are consistent with previous studies in other countries. Compared with older generations, men and women born in the late 1960s may have been subject to early exposures that increased their lifelong susceptibility to obesity. PMID:20375843

  16. Role of leptin G-2548A polymorphism in age- and gender-specific development of obesity.

    PubMed

    Shahid, Adeela; Rana, Sobia; Mahmood, Saqib; Saeed, Shahid

    2015-09-01

    Leptin is involved in the regulation of food intake and energy expenditure, and therefore, is central to adipositysensing pathway. We examined the relationship of the leptin G-2548A polymorphism with obesity and obesityrelated anthropometric and metabolic parameters in a total of 394 (239 obese and 155 non-obese) subjects between 5 and 45 years of age. Body weight, height, waist circumference (WC), hip circumference (HC) and blood pressure (BP) were measured. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Levels of fasting blood glucose (FBG), insulin, leptin and leptin receptor were determined, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The LEP G-2548A polymorphism showed association with obesity in children and adolescents (less than or equal to 18 years of age) but not in adults. However, analysis by gender stratification revealed association with obesity in girls only. In addition, G-2548A polymorphism showed association with BMI, WC, HC, fasting blood glucose and serum leptin levels. This suggests that G-2548A polymorphism may influence the susceptibility to metabolic disturbances and obesity at an early life. Further investigation with a larger sample size is required to validate the effect of LEP G-2548A polymorphism in obese Pakistani girls. PMID:26333398

  17. Linking obesity with type 2 diabetes: the role of T-bet

    PubMed Central

    Wali, Jibran A; Thomas, Helen E; Sutherland, Andrew PR

    2014-01-01

    Obesity is a major predisposing factor for the development of type 2 diabetes (T2D) and is an escalating public health issue around the world. The transition from obesity to T2D is preceded by the induction of a state of insulin resistance, which occurs in response to genetic factors and environmental influences, such as diet. Recent advances have implicated inflammatory immune cells and cytokines as critical pathogenic mediators of insulin resistance and T2D. In particular proinflammatory T helper (Th)1 cells and M1 macrophages are recruited to adipose tissue in response to high fat diet and directly promote the development of insulin resistance. The function of these two cell types is linked by the actions of the cytokine interferon (IFN)γ and one of its major transcriptional regulators T-bet. Recent studies in animal models of T2D demonstrate that T-bet is critical for the development of insulin resistance in response to high fat diet as T-bet-deficient animals are protected from the development of insulin resistance. These data indicate that T-bet and type 1 immunity may constitute novel sites of therapeutic intervention for the treatment of insulin resistance and T2D, in obese human patients. PMID:25092994

  18. Effect of sitagliptin on epicardial fat thickness in subjects with type 2 diabetes and obesity: a pilot study.

    PubMed

    Lima-Martínez, Marcos M; Paoli, Mariela; Rodney, Marianela; Balladares, Nathalie; Contreras, Miguel; D'Marco, Luis; Iacobellis, Gianluca

    2016-03-01

    The aim of the study was to assess the effect of sitagliptin addition on the epicardial adipose tissue (EAT) thickness in subjects with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. This was a 24-week interventional pilot study in 26 consecutive type 2 diabetic patients, 14 females and 12 males average age of 43.8 ± 9.0 years, with Hemoglobin A1c (HbA1c) ≥ 7% on metformin monotherapy. Subjects who met the inclusion criteria were added on sitagliptin and started on sitagliptin/metformin combination at the dosage of 50 mg/1000 mg twice daily. EAT and visceral and total body fat were measured, respectively, with echocardiography and bioelectrical impedance analysis at baseline and after 24 weeks of sitagliptin/metformin treatment in each subject. HbA1c and plasma lipids were also measured. EAT decreased significantly from 9.98 ± 2.63 to 8.10 ± 2.11 mm, p = 0.001, accounting for a percentage of reduction (∆%) of -15% after 24 weeks of sitagliptin addition, whereas total body fat percentage, visceral fat, and body mass index (BMI), decreased by 8, 12, and 7%, respectively (p = 0.001 for all). After 6 month, EAT ∆% was significantly correlated with ∆% of visceral fat (r = 0.456; p = 0.01), whereas no correlation with either BMI ∆% (r = 0.292; p = 0.147) or HbA1c ∆% was found. The addition of Sitagliptin produced a significant and rapid reduction of EAT, marker of organ-specific visceral fat, in overweight/obese individuals with type 2 diabetes inadequately controlled on metformin monotherapy. EAT as measured with ultrasound can serve as no invasive and accurate marker of visceral fat changes during pharmaceutical interventions targeting the fat. PMID:26233684

  19. Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes.

    PubMed

    Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

    2016-04-29

    Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function. PMID:26933035

  20. Prevalence of Diabetes, Obesity and Dyslipidaemia in Persons within High and Low Income Groups Living in North and South Trinidad

    PubMed Central

    Rahming, Valendrea; Raghunanan, Yudestri; Raghoonath, Chandani; Rahman, Adriel; Rajh, Dillon; Rambadan, Sherry; Ramdass, Nandini

    2016-01-01

    Introduction Diabetes Mellitus, obesity and dyslipidaemia are metabolic disorders characterized by similar risk factors, complications and outcomes including stroke, insulin resistance, MI and even death. Studies have indicated that impoverished and low income areas of developing countries are more prone to increasing obesity which when uncontrolled can lead to diabetes mellitus and dyslipidaemia. Aim The study was aimed to compare the prevalence of diabetes mellitus, obesity and dyslipidaemia in high and low income groups of North and South Trinidad, to determine factors that contribute to its prevalence and to observe any associations between the three aforementioned diseases. Materials and Methods The cross-sectional study was conducted on 200 participants who visited the two major hospitals at south and north Trinidad where the mean differences between fasting glucose, lipid profile, BMI, waist and hip ratio and blood pressure of both diabetic and non-diabetic participants were obtained via questionnaires and then analysed using SPSS. Results Residents of south Trinidad showed a higher proportion of persons with diabetes and dyslipidaemia at 68.6% and 52% when compared to 28.6% and 27% respectively for the north population. Those from north Trinidad showed a higher prevalence of obesity at 45.9% with higher income levels. About 17.3% participants smoked or were exposed to cigarettes in north compared to 9.8% of participants whom smoked or were exposed to cigarettes in south. North had 2% of alcohol consumed daily and 3.9% consumed alcohol daily in south. In north, 21.4% of participants were stressed when compared to 18.6% from south. Conclusion A significant correlation was established between cholesterol, LDL and triglycerides which lead to the conclusion that obesity is caused by dyslipidaemia. Also, our study concluded that stress and dyslipidaemia are income related. PMID:27437244

  1. Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects

    PubMed Central

    Emerenziani, Gian Pietro; Gallotta, Maria Chiara; Migliaccio, Silvia; Greco, Emanuela A.; Marocco, Chiara; di Lazzaro, Luca; Fornari, Rachele; Lenzi, Andrea; Baldari, Carlo; Guidetti, Laura

    2016-01-01

    Aim of the study was to examine cardiorespiratory parameters at individual ventilatory threshold (IVT) and peak exercise capacity (V˙O2peak) in outpatient diabetic and sarcopenic obese subjects. Seventeen obese subjects (BMI: 36.6 ± 4.1 kg·m−1) and sixteen SO subjects (BMI: 37.0 ± 7.3 kg·m−1) were compared with sixteen T2DM subjects (BMI: 37.7 ± 5.6 kg·m−1). All groups performed an incremental exercise test on a treadmill according to their physical ability. V˙O2peak, %HRmax, and maximal metabolic equivalent (METmax) were evaluated at maximal effort. Moreover, V˙O2ivt, %V˙O2peak, %HRmax, %HRR, ΔHR, and METivt were assessed at IVT. No significant differences were found in any physiological parameters at maximal effort (V˙O2peak, %HRmax, and METmax) in all groups. On the contrary, V˙O2ivt, %V˙O2peak, %HRmax, %HRR, ΔHR, and METivt were significantly lower in T2DM subjects as compared to OB and SO subjects at IVT (p < 0.05). Our results show that while at maximal effort there are no differences among groups, at IVT the physiological parameters are lower in T2DM subjects than in OB and SO subjects. Therefore, due to the differences observed in the groups, we suggest usng the IVT as a useful parameter to prescribe aerobic exercise in obese with sarcopenia or diabetes mellitus conditions. PMID:26884760

  2. The non-obese diabetic mouse sequence, annotation and variation resource: an aid for investigating type 1 diabetes

    PubMed Central

    Steward, Charles A.; Gonzalez, Jose M.; Trevanion, Steve; Sheppard, Dan; Kerry, Giselle; Gilbert, James G. R.; Wicker, Linda S.; Rogers, Jane; Harrow, Jennifer L.

    2013-01-01

    Model organisms are becoming increasingly important for the study of complex diseases such as type 1 diabetes (T1D). The non-obese diabetic (NOD) mouse is an experimental model for T1D having been bred to develop the disease spontaneously in a process that is similar to humans. Genetic analysis of the NOD mouse has identified around 50 disease loci, which have the nomenclature Idd for insulin-dependent diabetes, distributed across at least 11 different chromosomes. In total, 21 Idd regions across 6 chromosomes, that are major contributors to T1D susceptibility or resistance, were selected for finished sequencing and annotation at the Wellcome Trust Sanger Institute. Here we describe the generation of 40.4 mega base-pairs of finished sequence from 289 bacterial artificial chromosomes for the NOD mouse. Manual annotation has identified 738 genes in the diabetes sensitive NOD mouse and 765 genes in homologous regions of the diabetes resistant C57BL/6J reference mouse across 19 candidate Idd regions. This has allowed us to call variation consequences between homologous exonic sequences for all annotated regions in the two mouse strains. We demonstrate the importance of this resource further by illustrating the technical difficulties that regions of inter-strain structural variation between the NOD mouse and the C57BL/6J reference mouse can cause for current next generation sequencing and assembly techniques. Furthermore, we have established that the variation rate in the Idd regions is 2.3 times higher than the mean found for the whole genome assembly for the NOD/ShiLtJ genome, which we suggest reflects the fact that positive selection for functional variation in immune genes is beneficial in regard to host defence. In summary, we provide an important resource, which aids the analysis of potential causative genes involved in T1D susceptibility. Database URLs: http://www.sanger.ac.uk/resources/mouse/nod/; http://vega

  3. Wheezing, Sleeping, and Worrying: The Hidden Risks of Asthma and Obesity in School-Age Children

    ERIC Educational Resources Information Center

    Fiese, Barbara H.; Everhart, Robin S.; Wildenger, Leah

    2009-01-01

    The present study investigated the co-occurrence of asthma and obesity in a sample of 193 children (mean age = 7.76 years). Specifically, this study was interested in delineating the associated comorbidities of internalizing symptoms and sleep disruptions among younger (younger than 7 years) and older elementary age children with asthma who were…

  4. Obesity and Developmental Functioning among Children Aged 2-4 Years. National Poverty Center Working Paper Series #08-07

    ERIC Educational Resources Information Center

    Cawley, John; Spiess, C. Katharina

    2008-01-01

    In developed countries, obesity tends to be associated with worse labor market outcomes. One possible reason is that obesity leads to less human capital formation early in life. This paper investigates the association between obesity and the developmental functioning of children at younger ages (2-4 years) than ever previously examined. Data from…

  5. Characteristics of Physician Office Visits for Obesity by Adults Aged 20 and Over: United States, 2012.

    PubMed

    Talwalkar, Anjali; McCarty, Frances

    2016-03-01

    In 2011–2014, current asthma prevalence was higher among adults with obesity compared with adults in lower weight categories. This pattern was consistent across most demographic subgroups, except among men, for whom no statistically significant difference in current asthma prevalence by weight status was observed. Other epidemiologic studies of asthma prevalence have shown conflicting results about whether obesity is a risk factor for asthma among males. By race and Hispanic origin, current asthma prevalence was highest among adults with obesity for all groups. Patterns differed slightly among groups. For non-Hispanic black and Hispanic adults, prevalence for those with obesity was higher than for those in the normal weight and overweight categories. For non-Hispanic white adults, there was no signficant difference in asthma prevalence between the obese and overweight categories. For all age groups, current asthma prevalence was highest among adults with obesity, and there was no significant difference in asthma prevalence between those in the normal weight and overweight categories. There was an increasing trend in asthma prevalence as weight increased that was observed most clearly in the 60 and over age group. From 2001 to 2014, there was an increasing trend in current asthma prevalence among adults overall and among overweight adults. However, no significant trend was observed among adults in other weight categories. Findings from an American Thoracic Society workshop on obesity and asthma concluded that obesity is a major risk factor for asthma, and that obesity-related asthma is likely different from other types of asthma (e.g., allergic, occupational, exercise-induced, nocturnal, aspirin-sensitive, and severe asthma). PMID:27018815

  6. Lipogenic potential of liver from morbidly obese patients with and without non-insulin-dependent diabetes

    SciTech Connect

    Barakat, H.A.; McLendon, V.D.; Carpenter, J.W.; Marks, R.H.; Legett, N.; O'Brien, K.; Caro, J.F. )

    1991-03-01

    Intra-abdominal liver biopsies were obtained during surgery from fasted obese patients with non-insulin-dependent diabetes mellitus (NIDDM), obese normoglycemic controls, and lean controls. Lipid synthesis was studied in freshly isolated hepatocytes and liver homogenates from the three groups of subjects. Incorporation of 3H2O into the lipids of hepatocytes was determined in the absence and presence of insulin (0.1 mumol/L). The activities of five enzymes involved in fatty acid synthesis, and the incorporation of 14C-glycerol-3-phosphate into lipids were determined in liver homogenates. Basal lipid synthesis by hepatocytes was not different in the three groups of patients. Insulin stimulated lipogenesis by 8% +/- 30% in the lean controls, 33% +/- 8% in the obese controls and 17% +/- 6% in the NIDDM patients. No significant differences in the activities of the five enzymes that are involved in de novo fatty acid synthesis among the three groups of patients were observed. Similarly, incorporation of 14C-glycerol-3-phosphate by liver homogenates, in the presence of saturating or submaximal concentrations of fatty acids, did not differ among the three groups. These results show that under the experimental conditions of this study, including the fasted state of the patients, the basal capacity of liver of NIDDM patients to synthesize fatty acids or glycerides is the same as that of liver from obese and lean controls. Thus, it is likely that an increase in fatty acid flux into a liver with normal lipogenic potential may contribute to the increased synthesis of triglycerides by the liver of these patients in vivo.

  7. The Geography of Diabetes among the General Adults Aged 35 Years and Older in Bangladesh: Recent Evidence from a Cross-Sectional Survey

    PubMed Central

    Khan, Md. Mobarak Hossain; Gruebner, Oliver; Kraemer, Alexander

    2014-01-01

    Objective To report geographical variations of sex-specific diabetes by place of residence (large cities/city corporations, small towns/other urban areas, rural areas) and region of residence (divided into seven divisions) among general adults (35+ years of age) in Bangladesh. Methods The recent cross-sectional data, extracted from the nationally representative Bangladesh Demographic and Health Survey 2011, was used. A total of 3,720 men and 3,823 women aged 35+ years, who participated in the fasting blood sugar testing, were analysed. Any person with either fasting plasma glucose level (mmol/L) ≥7.0 or taking medication for diabetes was considered as a person with diabetes. Results The prevalence of diabetes was 10.6% in men and 11.3% in women. Bivariable analyses indicated significant variations of diabetes by both geographical variables. The prevalence was highest in city corporations (men 18.0%, women 22.3%), followed by small towns (men 13.6%, women 15.2%) and rural areas (men 9.3%, women 9.5%). Regional disparities in diabetes prevalence were also remarkable, with the highest prevalence in Chittagong division and lowest prevalence in Khulna division. Multivariable logistic regression analyses provided mixed patterns of geographical disparities (depending on the adjusted variables). Some other independent risk factors for diabetes were advancing age, higher level of education and wealth, having TV (a proxy indicator of physical activity), overweight/obesity and hypertension. Conclusions Over 10% of the general adults aged 35 years and older were having diabetes. Most of the persons with diabetes were unaware of this before testing fasting plasma glucose level. Although significant disparities in diabetes prevalence by geographical variables were observed, such disparities are very much influenced by the adjusted variables. Finally, we underscore the necessities of area-specific strategies including early diagnosis and health education programmes for changing

  8. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with Type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Overweight and obese individuals are encouraged to lose 5–10% of their body weight to improve cardiovascular disease (CVD) risk, but data supporting this recommendation are limited, particularly for individuals with type 2 diabetes. We conducted an observational analysis of participants in the Look ...

  9. 25-hydroxyvitamin D in obese youth across the spectrum of glucose tolerance from normal to prediabetes to type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and Beta-cell ...

  10. The Role of Underlying Type 2 Diabetes Mellitus and Obesity in Ozone-Induced Pulmonary Injury and Metabolic Impairment

    EPA Science Inventory

    RATIONALE: A growing body of evidence indicates an association between air pollution exposure and metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). We have recently demonstrated that an acute exposure to ozone in metabolically normal rat strains produces h...

  11. Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast High Throughput Data

    EPA Science Inventory

    Background: Diabetes and obesity are major threats to public health in the US and abroad. Understanding the role chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals ...

  12. Endurance exercise training programs intestinal lipid metabolism in a rat model of obesity and type 2 diabetes

    PubMed Central

    Hung, Yu‐Han; Linden, Melissa A.; Gordon, Alicia; Scott Rector, R.; Buhman, Kimberly K.

    2015-01-01

    Abstract Endurance exercise has been shown to improve metabolic outcomes in obesity and type 2 diabetes; however, the physiological and molecular mechanisms for these benefits are not completely understood. Although endurance exercise has been shown to decrease lipogenesis, promote fatty acid oxidation (FAO), and increase mitochondrial biosynthesis in adipose tissue, muscle, and liver, its effects on intestinal lipid metabolism remain unknown. The absorptive cells of the small intestine, enterocytes, mediate the highly efficient absorption and processing of nutrients, including dietary fat for delivery throughout the body. We investigated how endurance exercise altered intestinal lipid metabolism in obesity and type 2 diabetes using Otsuka Long‐Evans Tokushima Fatty (OLETF) rats. We assessed mRNA levels of genes associated with intestinal lipid metabolism in nonhyperphagic, sedentary Long‐Evans Tokushima Otsuka (LETO) rats (L‐Sed), hyperphagic, sedentary OLETF rats (O‐Sed), and endurance exercised OLETF rats (O‐EndEx). O‐Sed rats developed hyperphagia‐induced obesity (HIO) and type 2 diabetes compared with L‐Sed rats. O‐EndEx rats gained significantly less weight and fat pad mass, and had improved serum metabolic parameters without change in food consumption compared to O‐Sed rats. Endurance exercise resulted in dramatic up‐regulation of a number of genes in intestinal lipid metabolism and mitochondrial content compared with sedentary rats. Overall, this study provides evidence that endurance exercise programs intestinal lipid metabolism, likely contributing to its role in improving metabolic outcomes in obesity and type 2 diabetes. PMID:25602012

  13. Genetic Analysis of Substrain Divergence in Non-Obese Diabetic (NOD) Mice.

    PubMed

    Simecek, Petr; Churchill, Gary A; Yang, Hyuna; Rowe, Lucy B; Herberg, Lieselotte; Serreze, David V; Leiter, Edward H

    2015-05-01

    The non-obese diabetic (NOD) mouse is a polygenic model for type 1 diabetes that is characterized by insulitis, a leukocytic infiltration of the pancreatic islets. During ~35 years since the original inbred strain was developed in Japan, NOD substrains have been established at different laboratories around the world. Although environmental differences among NOD colonies capable of impacting diabetes incidence have been recognized, differences arising from genetic divergence have not been analyzed previously. We use both mouse diversity array and whole-exome capture sequencing platforms to identify genetic differences distinguishing five NOD substrains. We describe 64 single-nucleotide polymorphisms, and two short indels that differ in coding regions of the five NOD substrains. A 100-kb deletion on Chromosome 3 distinguishes NOD/ShiLtJ and NOD/ShiLtDvs from three other substrains, whereas a 111-kb deletion in the Icam2 gene on Chromosome 11 is unique to the NOD/ShiLtDvs genome. The extent of genetic divergence for NOD substrains is compared with similar studies for C57BL6 and BALB/c substrains. As mutations are fixed to homozygosity by continued inbreeding, significant differences in substrain phenotypes are to be expected. These results emphasize the importance of using embryo freezing methods to minimize genetic drift within substrains and of applying appropriate genetic nomenclature to permit substrain recognition when one is used. PMID:25740934

  14. Circulating and visceral adipose miR-100 is down-regulated in patients with obesity and Type 2 diabetes.

    PubMed

    Pek, Sharon Li Ting; Sum, Chee Fang; Lin, Michelle Xueqin; Cheng, Anton Kui Sing; Wong, Michael Tack Keong; Lim, Su Chi; Tavintharan, Subramaniam

    2016-05-15

    Obesity is a major public health problem conferring substantial excess risk for Type 2 diabetes (T2D). The role of microRNAs (miRNAs) in obesity and adipose tissue is not clearly defined. We hypothesize that circulating miRNA expression profiles vary according to differences in body mass index (BMI) and T2D and circulating miRNAs may reflect adipose tissue expression. Compared to healthy, lean individuals, circulating miR-100 was significantly lower in obese normoglycemic subjects and subjects with T2D. In visceral adipose tissue, expression of miR-100 was lower from obese subjects with T2D compared to obese subjects without T2D. miR-100 expression was significantly lower after adipogenic induction in human visceral, subcutaneous adipocytes and 3T3-L1 adipocytes. miR-100 reduced expression of mammalian target of rapamycin (mTOR) and Insulin Growth Factor Receptor (IGFR) directly. Differentiation of 3T3-L1 was accelerated by inhibition of miR-100 and reduced by miR-100 mimic transfection. Our data provide the first evidence of an association of circulating miR-100 with obesity and diabetes. Additionally, our in-vitro findings, and the miR-100 expression patterns in site-specific adipose tissue suggest miR-100 to modulate IGFR, mTOR and mediate adipogenesis. PMID:26973292

  15. Achieving Health for a Lifetime: A Community Engagement Assessment Focusing on School-Age Children to Decrease Obesity in Durham, North Carolina

    PubMed Central

    Corsino, Leonor; McDuffie, Jennifer R.; Kotch, Jonathan; Coeytaux, Remy; Fuemmeler, Bernard F.; Murphy, Gwen; Miranda, Marie Lynn; Poirier, Brenda; Morton, Janet; Reese, David; Baker, Sharon; Carter, Heidi; Freeman, Rebecca; Blue, Colleen; Yancy, William S.

    2013-01-01

    BACKGROUND Obesity is a prominent problem in the United States and in North Carolina. One way of combating it is with community-engaged interventions that foster collaboration between health-oriented organizations and community residents. PURPOSE Our purpose was to assemble a multifaceted group in Durham, North Carolina, to identify factors affecting obesity-related lifestyle behaviors; assess policies, resources, and the population's perception of the problem of obesity; and develop plans to improve health outcomes related to obesity. METHODS A team consisting of more than 2 dozen partners was assembled to form Achieving Health for a Lifetime (AHL) in order to study and address obesity in the community, initially focusing on elementary school-age children. The team developed a resource guide by collecting information by telephone interviews of provider organizations; geospatial resource maps were created using high-resolution geographic information systems, Duke's Data Support Repository, and county and city records; and focus groups were conducted using the nominal group technique. RESULTS The AHL team, in collaboration with 2 other teams focused on diabetes and cardiovascular disease, identified 32 resources for diabetes, 20 for obesity, and 13 for cardiovascular disease. Using Geographic Information Systems (GIS), the team identified an area of Durham that had only 1 supermarket, but 34 fast-food restaurants and 84 convenience stores. LIMITATIONS The focus on particular neighborhoods means that the information obtained might not pertain to all neighborhoods. CONCLUSION The AHL team was able to assemble a large community partnership in Durham that will allow the members of the community to continue to work toward making residents healthier. Communities facing similar challenges can learn from this experience. PMID:23530374

  16. The association of obesity with hearing thresholds in women aged 18-40 years.

    PubMed

    Üçler, Rıfkı; Turan, Mahfuz; Garça, Fatih; Acar, İsmail; Atmaca, Murat; Çankaya, Hakan

    2016-04-01

    An elevation in hearing thresholds and decrease in hearing sensitivity in adults, particularly due to aging, are quite common. Recent studies have shown that, apart from aging, various other factors also play a role in auditory changes. Studies on the association of hearing loss (HL) with obesity are limited in advanced age cases and present contradictions. In this study, the association between obesity and hearing thresholds in women aged 18-40 years has been assessed. Forty women diagnosed with obesity (mean age, 31.8 years) and 40 healthy non-obese female controls (mean age, 30.5 years) were included in this prospective study. Each subject was tested with low (250, 500, 1000 and 2000 Hz) and high (4000, 6000 and 8000 Hz) frequency audiometry. In the case and control groups, the average hearing thresholds at low frequencies were 16.03 ± 4.72 and 16.15 ± 2.72 (p = 0.885) for the right ear, respectively, and 16.15 ± 5.92 and 14.71 ± 3.18 (p = 0.180) for the left ear, respectively. The average hearing threshold levels at high frequencies were 20.70 ± 10.23 and 15.33 ± 3.87 (p = 0.003), respectively, for the right ear, and 22.91 ± 15.54 and 15.87 ± 4.35 (p = 0.007), respectively, for the left ear with statistical significance. This is the first report on the association of obesity with hearing threshold in women aged 18-40 years. We have demonstrated that obesity may affect hearing function, particularly that related to high frequencies. Hearing loss can be prevented by avoidance or control of obesity and its risk factors. Moreover, an auditory screening of obese cases at an early stage may provide early diagnosis of HL and may also contribute to their awareness in the fight against obesity. PMID:26429780

  17. Increased Circulating ANG II and TNF-α Represents Important Risk Factors in Obese Saudi Adults with Hypertension Irrespective of Diabetic Status and BMI

    PubMed Central

    Al-Daghri, Nasser M.; Bindahman, Lotfi S.; Al-Attas, Omar S.; Saleem, Tahia H.; Alokail, Majed S.; Alkharfy, Khalid M.; Draz, Hossam M.; Yakout, Sobhy; Mohamed, Amany O.; Harte, Alison L.; McTernan, Philip G.

    2012-01-01

    Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk. PMID:23251471

  18. Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction.

    PubMed

    Lopez, Elizabeth F; Kabarowski, Janusz H; Ingle, Kevin A; Kain, Vasundhara; Barnes, Stephen; Crossman, David K; Lindsey, Merry L; Halade, Ganesh V

    2015-02-15

    Polyunsaturated fatty acid (PUFA) intake has increased over the last 100 yr, contributing to the current obesogenic environment. Obesity and aging are prominent risk factors for myocardial infarction (MI). How obesity interacts with aging to alter the post-MI response, however, is unclear. We tested the hypothesis that obesity in aging mice would impair the resolution of post-MI inflammation. PUFA diet (PUFA aging group) feeding to 12-mo-old C57BL/6J mice for 5 mo showed higher fat mass compared with standard lab chow (LC)-fed young (LC young group; 3-5 mo old) or aging alone control mice (LC aging group). LC young, LC aging, and PUFA aging mice were subjected to coronary artery ligation to induce MI. Despite similar infarct areas post-MI, plasma proteomic profiling revealed higher VCAM-1 in the PUFA aging group compared with LC young and LC aging groups, leading to increased neutrophil infiltration in the PUFA aging group (P<0.05). Macrophage inflammatory protein-1γ and CD40 were also increased at day 1, and myeloperoxidase remained elevated at day 5, an observation consistent with delayed wound healing in the PUFA aging group. Lipidomic analysis showed higher levels of arachidonic acid and 12(S)-hydroxyeicosatetraenoic acid at day 1 post-MI in the PUFA aging group compared with the LC aging group (all P<0.05), thereby mediating neutrophil extravasation in the PUFA aging group. The inflammation-resolving enzymes 5-lipoxygenase, cyclooxygenase-2, and heme oxyegnase-1 were altered to delay wound healing post-MI in the PUFA aging group compared with LC young and LC aging groups. PUFA aging magnifies the post-MI inflammatory response and impairs the healing response by stimulating prolonged neutrophil trafficking and proinflammatory lipid mediators. PMID:25485899

  19. Obesity