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Sample records for age obesity diabetes

  1. Obesity and diabetes.

    PubMed

    Riobó Serván, Pilar

    2013-09-01

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

  2. 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.

  3. Methylglyoxal, obesity, and diabetes.

    PubMed

    Matafome, Paulo; Sena, Cristina; Seiça, Raquel

    2013-06-01

    Methylglyoxal (MG) is a highly reactive compound derived mainly from glucose and fructose metabolism. This metabolite has been implicated in diabetic complications as it is a strong AGE precursor. Furthermore, recent studies suggested a role for MG in insulin resistance and beta-cell dysfunction. Although several drugs have been developed in the recent years to scavenge MG and inhibit AGE formation, we are still far from having an effective strategy to prevent MG-induced mechanisms. This review summarizes the mechanisms of MG formation, detoxification, and action. Furthermore, we review the current knowledge about its implication on the pathophysiology and complications of obesity and diabetes.

  4. 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

    2015-10-06

    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.

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

    PubMed Central

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

    2015-01-01

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

  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. Altered basal and stimulated accumbens dopamine release in obese OLETF rats as a function of age and diabetic status

    PubMed Central

    Anderzhanova, Elmira; Covasa, Mihai; Hajnal, Andras

    2011-01-01

    The Otsuka Long Evans Tokushima Fatty (OLETF) rat lacking the CCK-1 receptor is hyperphagic, prefers palatable and high caloric meals, and gradually develops obesity and type-2 diabetes. To determine dopamine levels in this strain, we used in-vivo quantitative (no-net flux) microdialyis at three different ages representing non-diabetic (8 weeks), pre-diabetic (18 weeks), and diabetic (56 weeks) stages in OLETF and age-matched lean LETO controls. Results showed significantly elevated basal dopamine levels in the caudomedial nucleus accumbens of OLETF rats compared to LETO at younger ages (8 weeks: 20.10 ± 5.61 nM vs. 15.85 ± 5.63 nM; 18 weeks: 7.37 ± 3.71 nM vs. 4.75 ± 1.25 nM, Mean ± SD). In contrast, at 56 weeks of age, a profound decline in extracellular dopamine concentrations was seen in both strains with a tendency for a greater effect in OLETF rats (1.78 ± 0.40 nM vs. 2.39 ± 0.42 nM). Further, extracellular fraction, an index for reuptake, was higher in 56-week old OLETF compared to LETO (0.648 ± 0.049 vs. 0.526 ± 0.057). Potassium-stimulated dopamine efflux revealed an increased capacity of vesicular pool in OLETF rats compared to LETO across all age groups with an accentuated strain difference at 56 weeks. These findings demonstrate altered striatal dopamine functions (i.e. increased stimulated release and uptake) in obese OLETF rat. This could be due to the lack of functional CCK-1 receptors, or metabolic and hormonal factors associated with the development of obesity and insulin resistance, or both. PMID:17553848

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

    PubMed

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

    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.

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

    PubMed Central

    Salmon, Adam B.

    2016-01-01

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

  10. Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes.

    PubMed

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

    2017-04-01

    Human age-related diseases, including obesity and type 2 diabetes (T2DM), have long been associated to mitochondrial dysfunction; however, the role for adipose tissue mitochondria in these conditions remains unknown. We have tackled the impact of aging and T2DM on adipocyte mitochondria from obese patients by quantitating not only the corresponding abundance changes of proteins, but also the redox alterations undergone by Cys residues thereof. For that, we have resorted to a high-throughput proteomic approach based on isobaric labeling, liquid chromatography and mass spectrometry. The alterations undergone by the mitochondrial proteome revealed aging- and T2DM-specific hallmarks. Thus, while a global decrease of oxidative phosphorylation (OXPHOS) subunits was found in aging, the diabetic patients exhibited a reduction of specific OXPHOS complexes as well as an up-regulation of the anti-oxidant response. Under both conditions, evidence is shown for the first time of a link between increased thiol protein oxidation and decreased protein abundance in adipose tissue mitochondria. This association was stronger in T2DM, where OXPHOS mitochondrial- vs. nuclear-encoded protein modules were found altered, suggesting impaired mitochondrial protein translocation and complex assembly. The marked down-regulation of OXPHOS oxidized proteins and the alteration of oxidized Cys residues related to protein import through the redox-active MIA (Mitochondrial Intermembrane space Assembly) pathway support that defects in protein translocation to the mitochondria may be an important underlying mechanism for mitochondrial dysfunction in T2DM and physiological aging. The present draft of redox targets together with the quantification of protein and oxidative changes may help to better understand the role of oxidative stress in both a physiological process like aging and a pathological condition like T2DM.

  11. Pediatric obesity & type 2 diabetes.

    PubMed

    Dea, Tara L

    2011-01-01

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

  12. [Obesity and diabetes mellitus].

    PubMed

    Tron'ko, N D; Zak, K P

    2013-12-01

    New literature data and the results of own researches concerning the role of excessive body weight and the development of type 2 diabetes mellitus in humans are presented in the analytical review. Inaccordance with current insights, obesity and type 2 diabetes are considered diseases of inflammatory nature, characterized by systemic chronic low-grade inflammation, where different kinds of cytokines are cardinally involved. Unfavourable life style, i.e. excessive, high-energy, and irrational nutrition--an excessive consumption of animal fats and foods containing the high amount of glucose and starch with an insufficient use of high fiber vegetables, fish and vitamin D, and also sedentary, inactive life style leads to adipocyte hypertrophy and migration of M1 macrophages into the adipose tissue (AT). As a result, there is a low-grade inflammation accompanied by an increased production of proinflammatory cytokines (IL-1, IL-6, TNF-α, etc.), adipokines (leptin, resistin, visfatin etc.) and chemokines (CCL2, CCL5, CCL26 and CX3C). Under the influence of these cytokines, on the one hand, IR "is emerged", and on the other--there is apoptosis of the β-cells, that should be followed by the occurrence of clinically diagnosed type 2 diabetes. However, there is also the opposite system in humans, protecting the organism from the development of type 2 diabetes, and including an increase in the formation of M2 macrophages and the increased formation of secretion of antidiabetic cytokines (IL-4, IL-10, IL-13, etc.) and adiponectin.

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

    PubMed

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

    2013-07-01

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

  14. The Use of a Chronic Disease and Risk Factor Surveillance System to Determine the Age, Period and Cohort Effects on the Prevalence of Obesity and Diabetes in South Australian Adults - 2003–2013

    PubMed Central

    Taylor, Anne W.; Shi, Zumin; Montgomerie, Alicia; Dal Grande, Eleonora; Campostrini, Stefano

    2015-01-01

    Background Age, period and cohort (APC) analyses, using representative, population-based descriptive data, provide additional understanding behind increased prevalence rates. Methods Data on obesity and diabetes from the South Australian (SA) monthly chronic disease and risk factor surveillance system from July 2002 to December 2013 (n = 59,025) were used. Age was the self-reported age of the respondent at the time of the interview. Period was the year of the interview and cohort was age subtracted from the survey year. Cohort years were 1905 to 1995. All variables were treated as continuous. The age-sex standardised prevalence for obesity and diabetes was calculated using the Australia 2011 census. The APC models were constructed with ‘‘apcfit’’ in Stata. Results The age-sex standardised prevalence of obesity and diabetes increased in 2002-2013 from 18.6% to 24.1% and from 6.2% to 7.9%. The peak age for obesity was approximately 70 years with a steady increasing rate from 20 to 70 years of age. The peak age for diabetes was approximately 80 years. There were strong cohort effects and no period effects for both obesity and diabetes. The magnitude of the cohort effect is much more pronounced for obesity than for diabetes. Conclusion The APC analyses showed a higher than expected peak age for both obesity and diabetes, strong cohort effects with an acceleration of risk after 1960s for obesity and after 1940s for diabetes, and no period effects. By simultaneously considering the effects of age, period and cohort we have provided additional evidence for effective public health interventions. PMID:25923664

  15. 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.

  16. [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.

  17. Effect of genetic background on the therapeutic effects of dehydroepiandrosterone (DHEA) in diabetes-obesity mutants and in aged normal mice.

    PubMed

    Coleman, D L; Schwizer, R W; Leiter, E H

    1984-01-01

    Dehydroepiandrosterone (DHEA) was fed at 0.1-0.4% in the diet to genetically diabetic (db/db) or obese (ob/ob) C57BL/KsJ (BL/Ks) or C57BL/6J (BL/6) mice. Treatment of BL/Ks-db/db or ob/ob mice with 0.4% DHEA prevented hyperglycemia, islet atrophy, and severe diabetes associated with this inbred background, but did not affect weight gain and food consumption. Homozygous obese (ob) or diabetes (db) mice on the BL/6 background were more sensitive to DHEA, and the mild, transient hyperglycemia associated with ob or db gene expression on the BL/6 inbred background could be prevented by 0.1% DHEA. Both body weight and food consumption were decreased in BL/6 mutants maintained on 0.1% DHEA whereas this effect was not seen in BL/Ks mutants fed up to 0.4% DHEA. Early therapy with 0.4% DHEA, initiated at 2 wk of age, prevented the development of most diabetes symptoms and decreased the rate of weight gain in pups of all genotypes. In addition to therapeutic effects on both obese mutants, DHEA effected significant changes in an aging study using normal BL/6 female mice. Four weeks of DHEA treatment initiated at 2 yr of age improved glucose tolerance and at the same time reduced plasma insulin to a "younger" level. This suggests that DHEA may act in insulin-resistant mutant mice and in aging normal mice to increase the sensitivity to insulin.

  18. Obesity, Diabetes and Cancer: A Mechanistic Perspective

    PubMed Central

    Cifarelli, V; Hursting, SD

    2016-01-01

    Nearly 35% of adults and 20% of children in the United States are obese, defined as having a body mass index (BMI) ≥ 30 kg/m2. Obesity is an established risk factor for many cancers, and obesity-associated metabolic perturbations often manifest in Type 2 diabetes mellitus and/or the metabolic syndrome. As part of the growth-promoting, proinflammatory microenvironment of the obese and/or diabetic state, crosstalk between macrophages, adipocytes, and epithelial cells occurs via metabolically-regulated hormones, cytokines, and other mediators to enhance cancer risk and/or progression. This review synthesizes the evidence on key biological mechanisms underlying the associations between obesity, diabetes and cancer, with particular emphasis on enhancements in growth factor signaling, inflammation, and vascular integrity processes. These interrelated pathways represent mechanistic targets for disrupting the obesity-diabetes-cancer link, and several diabetes drugs, such as metformin and rosiglitazone, are being intensely studied for repurposing as cancer chemopreventive agents.

  19. Obesity in the ageing man.

    PubMed

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

    2013-10-01

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

  20. 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

  1. Mechanism linking diabetes mellitus and obesity

    PubMed Central

    Al-Goblan, Abdullah S; Al-Alfi, Mohammed A; Khan, Muhammad Z

    2014-01-01

    Body mass index has a strong relationship to diabetes and insulin resistance. In obese individuals, the amount of nonesterified fatty acids, glycerol, hormones, cytokines, proinflammatory markers, and other substances that are involved in the development of insulin resistance, is increased. The pathogenesis in the development of diabetes is based on the fact that the β-islet cells of the pancreas are impaired, causing a lack of control of blood glucose. The development of diabetes becomes more inevitable if the failure of β-islet cells of the pancreas is accompanied by insulin resistance. Weight gain and body mass are central to the formation and rising incidence of type 1 and type 2 diabetes. This literature review will demonstrate the facts that link obesity with insulin resistance and pancreatic β-cell dysfunction. In conclusion, new approaches in managing and preventing diabetes in obese individuals must be studied and investigated based on the facts. PMID:25506234

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

    PubMed

    Abuyassin, B; Laher, I

    2015-09-08

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

  3. Obesity, diabetes, and risk of Parkinson's disease.

    PubMed

    Palacios, Natalia; Gao, Xiang; McCullough, Marjorie L; Jacobs, Eric J; Patel, Alpa V; Mayo, Tinisha; Schwarzschild, Michael A; Ascherio, Alberto

    2011-10-01

    The aim of this work was to investigate whether obesity and diabetes are related to risk of Parkinson's disease. We prospectively followed 147,096 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2005. Participants provided information on anthropometric variables and medical history at baseline and on waist circumference in 1997. Incident cases of Parkinson's disease (n = 656) were confirmed by treating neurologists and medical record review. Relative risks were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Neither body mass index nor waist circumference significantly predicted Parkinson's disease risk. Relative risk comparing individuals with a baseline body mass index of ≥ 30 to those with a body mass index <23 was 1.00 (95% confidence interval: 0.75, 1.34; P trend: 0.79), and that comparing individuals with a waist circumference in the top category (≥ 40.3 inches in men and ≥ 35 inches in women) to those in the bottom category (<34.5 inches in men and <28 inches in women) was 1.35 (95% confidence interval: 0.95, 1.93; P trend: 0.08). History of diabetes was not significantly associated with Parkinson's disease risk (combined relative risks = 0.88; 95% confidence interval: 0.62, 1.25; P heterogeneity = 0.96). In addition, neither body mass index at age 18 nor changes in weight between age 18 and baseline were significantly associated with Parkinson's disease risk. The results did not differ significantly by gender. Our results do not provide evidence for a relationship between body mass index, weight change, waist circumference, or baseline diabetes and risk of Parkinson's disease.

  4. Prioritizing Environmental Chemicals for Obesity and Diabetes ...

    EPA Pesticide Factsheets

    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 for testing beyond those already implicated in the literature is a challenge. This review is intended to help researchers generate hypotheses about chemicals potentially contributing to diabetes and obesity-related health outcomes by summarizing relevant findings from the US Environmental Protection Agency (EPA) ToxCast high-throughput screening (HTS) program. Objectives: To develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high throughput screening data. Methods: Identify ToxCast assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and beta cell function, adipocyte dierentiation, and feeding behavior) and present chemical screening data against those assay targets to identify chemicals of potential interest. Discussion: 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 from research papers and reviews published in the peer-reviewed literature. Testing of hypotheses based on ToxCast data will a

  5. Plasma adipokine and inflammatory marker concentrations are altered in obese, as opposed to non-obese, type 2 diabetes patients.

    PubMed

    Hansen, Dominique; Dendale, Paul; Beelen, Milou; Jonkers, Richard A M; Mullens, Annelies; Corluy, Luk; Meeusen, Romain; van Loon, Luc J C

    2010-06-01

    Elevated plasma free fatty acid (FFA), inflammatory marker, and altered adipokine concentrations have been observed in obese type 2 diabetes patients. It remains unclear whether these altered plasma concentrations are related to the diabetic state or presence of obesity. In this cross-sectional observational study, we compare basal plasma FFA, inflammatory marker, and adipokine concentrations between obese and non-obese type 2 diabetes patients and healthy, non-obese controls. A total of 20 healthy, normoglycemic males (BMI <30 kg/m(2)), 20 non-obese (BMI <30 kg/m(2)) and 20 obese (BMI >35 kg/m(2)) type 2 diabetes patients were selected to participate in this study. Groups were matched for age and habitual physical activity level. Body composition, glycemic control, and exercise performance capacity were assessed. Basal blood samples were collected to determine plasma leptin, adiponectin, resistin, tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and FFA concentrations. Plasma FFA, inflammatory marker (hsCRP, IL-6, TNFalpha), adipokine (adiponectin, resistin, leptin), and triglyceride concentrations did not differ between non-obese diabetes patients and healthy, normoglycemic controls. Plasma FFA, IL-6, hsCRP, leptin, and triglyceride levels were significantly higher in the obese diabetes patients when compared with the healthy normoglycemic controls (P < 0.05). Furthermore, plasma hsCRP and leptin levels were significantly higher in the obese versus non-obese diabetes patients (P < 0.05). Significant correlations between plasma parameters and glycemic control were observed, but disappeared after adjusting for trunk adipose tissue mass. Elevated plasma leptin, hsCRP, IL-6, and FFA concentrations are associated with obesity and not necessarily with the type 2 diabetic state.

  6. Structural renal changes in obesity and diabetes.

    PubMed

    Amann, Kerstin; Benz, Kerstin

    2013-01-01

    Overweight, obesity, and associated diseases represent an emerging problem, not only in Western countries but also in the developing world. They are now characterized as epidemic diseases. Obesity is particularly serious because its incidence in children and adolescents increased dramatically: it is estimated that in the United States every eighth adolescent suffers from obesity, which in the long run may reduce life expectancy in the population. Apart from cardiovascular disease (ie, blood pressure, stroke, and coronary heart disease), kidney diseases also have been shown to be associated with obesity. Epidemiologic studies have indicated that obesity can be a risk factor of chronic kidney disease irrespective of the presence or absence of diabetes, arterial hypertension, and other comorbidities. More evidence is accumulated on the link between chronic kidney disease in obesity and abnormalities in adipokine secretion (hyperleptinemia, lack of adiponectin), activation of the renin-angiotensin system, chronic inflammation, endothelial dysfunction, lipid accumulation, impaired renal hemodynamics, and diminished nephron number related to body mass. In general, obesity is known to aggravate the course of many primary renal diseases such as glomerulonephritides, but also impairs renal function after kidney transplantation. Microalbuminuria, proteinuria, hyperfiltration, and impaired renal function are associated with obesity. Histologically, secondary focal segmental sclerosis has been shown to be caused particularly by obesity. Of practical purpose for clinical nephrology, loss of body weight either by lifestyle modification or bariatric surgery improves albuminuria and hyperfiltration in obese patients, making renal disease in obesity accessible for prevention programs. This review specifically addresses the pathogenesis and morphology of renal functional and particularly structural changes in obesity and associated renal disease such as diabetic nephropathy.

  7. Obesity and related consequences to ageing.

    PubMed

    Jura, Magdalena; Kozak, Leslie P

    2016-02-01

    Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

  8. Obesity in young men, and individual and combined risks of type 2 diabetes, cardiovascular morbidity and death before 55 years of age: a Danish 33-year follow-up study

    PubMed Central

    Schmidt, Morten; Johannesdottir, Sigrun A; Lemeshow, Stanley; Lash, Timothy L; Ulrichsen, Sinna P; Bøtker, Hans Erik; Toft Sørensen, Henrik

    2013-01-01

    Objectives To examine the association between body mass index (BMI) in young adulthood and cardiovascular risks, including venous thromboembolism, before 55 years of age. Design Cohort study using population-based medical databases. Setting Outcomes registered from all hospitals in Denmark from 1977 onwards. Participants 6502 men born in 1955 and eligible for conscription in Northern Denmark. Main outcome measures Follow-up began at participants’ 22nd birthday and continued until death, emigration or 55 years of age, whichever came first. Using regression analyses, we calculated the risks and HRs, adjusting for cognitive test score and years of education. Results 48% of all obese young men (BMI ≥30 kg/m2) were either diagnosed with type 2 diabetes, hypertension, myocardial infarction, stroke or venous thromboembolism or died before reaching 55 years of age. Comparing obese men with normal weight men (BMI 18.5 to <25.0 kg/m2), the risk difference for any outcome was 28% (95% CI 19% to 38%) and the HR was 3.0 (95% CI 2.3 to 4.0). Compared with normal weight, obesity was associated with an event rate that was increased more than eightfold for type 2 diabetes, fourfold for venous thromboembolism and twofold for hypertension, myocardial infarction and death. Conclusions In this cohort of young men, obesity was strongly associated with adverse cardiometabolic events before 55 years of age, including venous thromboembolism. Compared with those of normal weight, young obese men had an absolute risk increase for type 2 diabetes, cardiovascular morbidity or premature death of almost 30%. PMID:23628994

  9. 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

  10. "Obesity" and "Clinical Obesity" Men's understandings of obesity and its relation to the risk of diabetes: A qualitative study

    PubMed Central

    Weaver, Nicola F; Hayes, Louise; Unwin, Nigel C; Murtagh, Madeleine J

    2008-01-01

    Background The 2007 Wanless report highlights the ever increasing problem of obesity and the consequent health problems. Obesity is a significant cause of diabetes. An increasing evidence base suggests that in terms of reducing diabetes and CVD risk, it is better to be "fit and fat" than unfit and of normal weight. There has been very little previous research into the understandings that men in the general population hold about the issues of weight, exercise and health; we therefore undertook this study in order to inform the process of health promotion and diabetes prevention in this group. Methods A qualitative study in North East England General Practice using a purposive sample of men aged 25 and 45 years (selection process designed to include 'normal', 'overweight' and 'obese' men). One to one audio-recorded semi structured interviews focused on: overweight and obesity, diet, physical activity and diabetes. Transcripts were initially analysed using framework analysis. Emerging themes interlinked. Results The men in this study (n = 17) understand the word obesity differently from the clinical definition; "obesity" was used as a description of those with fat in a central distribution, and understandings of the term commonly take into account fitness as well as weight. Men in their late 30s and early 40s described becoming more aware of health issues. Knowledge of what constitutes a 'healthy lifestyle' was generally good, but men described difficulty acting upon this knowledge for various reasons e.g. increasing responsibilities at home and at work. Knowledge of diabetes and the link between obesity and diabetes was poor. Conclusion Men in this study had a complex understanding of the interlinked importance of weight and fitness in relation to health. Obesity is understood as a description of people with centrally distributed fat, in association with low fitness levels. There is a need to increase understanding of the causes and consequences of diabetes

  11. 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

  12. Mortality as a function of obesity and diabetes mellitus.

    PubMed

    Pettitt, D J; Lisse, J R; Knowler, W C; Bennett, P H

    1982-03-01

    Mortality according to body mass index (weight/height2) was studied in 2197 Pima Indians aged 15-74 years, as part of the longitudinal study of diabetes begun in 1965 in the Gila River Indian Community of Arizona. The Pima Indians are a population with a high prevalence of obesity, and they have the highest known incidence of type II (non-insulin dependent) diabetes mellitus. Among males, mortality was greatest in those with a body mass index of at least 40 kg/m2, but obesity had little effect on mortality at body mass indices below 40 kg/m2. Age-specific death rates in women were not consistently related to obesity, although mortality in subjects with diabetes was higher than in those without. In men, diabetes had little effect on mortality. In this study, as in several other mortality studies, the lowest mortality rates were experienced by people with body weights well above those recommended as "desirable" by the Society of Actuaries in 1959. Thus, the applicability of the "desirable" weight standards in common use is questioned.

  13. Association of obesity and leptin with insulin resistance in type 2 diabetes mellitus in Indian population.

    PubMed

    Das, Piyali; Bhattacharjee, Debojyoti; Bandyopadhyay, Subir Kumar; Bhattacharya, Gorachand; Singh, Ramji

    2013-01-01

    Obesity and diabetes mellitus are two modern epidemics. But their interrelationship is debated. Here we explored the probable association among obesity, leptin and insulin resistance in type 2 diabetes mellitus. 60 recent onset (< 5 years) diabetics and age-sex matched 33 non diabetic controls were assessed for physical and chemical parameters like Body Mass Index, abdominal circumference, waist/hip ratio, fasting blood glucose, insulin and leptin. Degree of insulin resistance was calculated by HOMA-IR method (Homeostatic Model Assessment). All the physical parameters showed positive correlation with leptin and the HOMA-IR score, strength of association being highest between insulin resistance and abdominal circumference. Leptin and insulin resistance showed no correlation. Findings were lower in controls. Study concluded that, obesity mainly central type might be responsible for insulin resistance in type 2 diabetes mellitus where as leptin, a potential marker for obesity, may not. This perhaps points towards the multifactorial causation of insulin resistance in type 2 diabetes mellitus.

  14. Physical inactivity and obesity underlie the insulin resistance of aging.

    PubMed

    Amati, Francesca; Dubé, John J; Coen, Paul M; Stefanovic-Racic, Maja; Toledo, Frederico G S; Goodpaster, Bret H

    2009-08-01

    OBJECTIVE Age-associated insulin resistance may underlie the higher prevalence of type 2 diabetes in older adults. We examined a corollary hypothesis that obesity and level of chronic physical inactivity are the true causes for this ostensible effect of aging on insulin resistance. RESEARCH DESIGN AND METHODS We compared insulin sensitivity in 7 younger endurance-trained athletes, 12 older athletes, 11 younger normal-weight subjects, 10 older normal-weight subjects, 15 younger obese subjects, and 15 older obese subjects using a glucose clamp. The nonathletes were sedentary. RESULTS Insulin sensitivity was not different in younger endurance-trained athletes versus older athletes, in younger normal-weight subjects versus older normal-weight subjects, or in younger obese subjects versus older obese subjects. Regardless of age, athletes were more insulin sensitive than normal-weight sedentary subjects, who in turn were more insulin sensitive than obese subjects. CONCLUSIONS Insulin resistance may not be characteristic of aging but rather associated with obesity and physical inactivity.

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

    PubMed Central

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

    2016-01-01

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

  16. Phenotypic Type 2 Diabetes in Obese Youth

    PubMed Central

    Tfayli, Hala; Bacha, Fida; Gungor, Neslihan; Arslanian, Silva

    2009-01-01

    OBJECTIVE— Some obese youth with a clinical diagnosis of type 2 diabetes have evidence of islet cell autoimmunity with positive autoantibodies. In this study, we investigated the differences in insulin sensitivity and secretion between autoantibody-negative (Ab−) and -positive (Ab+) youth with clinically diagnosed type 2 diabetes in comparison with control subjects. RESEARCH DESIGN AND METHODS— Sixteen Ab− and 26 Ab+ clinically diagnosed type 2 diabetic patients and 39 obese control youth underwent evaluation of insulin sensitivity (3-h hyperinsulinemic-euglycemic clamp), substrate oxidation (indirect calorimetry), first- and second-phase insulin secretion (2-h hyperglycemic clamp), body composition and abdominal adiposity (dual energy X-ray absorptiometry and computed tomography scan, respectively), and glucose disposition index (first-phase insulin secretion × insulin sensitivity). RESULTS— Insulin-stimulated total, oxidative, and nonoxidative glucose disposal, and suppression of fat oxidation during hyperinsulinemia were significantly lower in Ab− compared with Ab+ clinically diagnosed type 2 diabetic and control subjects with no difference between the latter two. First- and second-phase insulin secretion and C-peptide were lower in Ab+ compared with Ab− type 2 diabetes. Glucose disposition index was not different between the Ab− and Ab+ clinically diagnosed type 2 diabetic patients, but both were significantly lower than that in control subjects. Systolic blood pressure and alanine aminotransferase were higher in Ab− versus Ab+ clinically diagnosed type 2 diabetic patients, whereas the frequency of ketonuria at diagnosis was higher in Ab+ versus Ab− patients. CONCLUSIONS— Islet-cell Ab− clinically diagnosed type 2 diabetic youth are characterized by severe insulin resistance and relative insulin deficiency, whereas Ab+ youth have severe insulin deficiency and β-cell failure. The former group has additional features of insulin

  17. [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.

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

    PubMed Central

    Karlamangla, Arun

    2016-01-01

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

  19. Metformin in obesity, cancer and aging: addressing controversies

    PubMed Central

    Berstein, Lev M.

    2012-01-01

    Metformin, an oral anti-diabetic drug, is being considered increasingly for treatment and prevention of cancer, obesity as well as for the extension of healthy lifespan. Gradually accumulating discrepancies about its effect on cancer and obesity can be explained by the shortage of randomized clinical trials, differences between control groups (reference points), gender- and age-associated effects and pharmacogenetic factors. Studies of the potential antiaging effects of antidiabetic biguanides, such as metformin, are still experimental for obvious reasons and their results are currently ambiguous. Here we discuss whether the discrepancies in different studies are merely methodological or inherently related to individual differences in responsiveness to the drug. PMID:22589237

  20. Metabolomic analyses for atherosclerosis, diabetes, and obesity

    PubMed Central

    2013-01-01

    Insulin resistance associated with type 2 diabetes mellitus (T2DM), obesity, and atherosclerosis is a global health problem. A portfolio of abnormalities of metabolic and vascular homeostasis accompanies T2DM and obesity, which are believed to conspire to lead to accelerated atherosclerosis and premature death. The complexity of metabolic changes in the diseases presents challenges for a full understanding of the molecular pathways contributing to the development of these diseases. The recent advent of new technologies in this area termed “Metabolomics” may aid in comprehensive metabolic analysis of these diseases. Therefore, metabolomics has been extensively applied to the metabolites of T2DM, obesity, and atherosclerosis not only for the assessment of disease development and prognosis, but also for the biomarker discovery of disease diagnosis. Herein, we summarize the recent applications of metabolomics technology and the generated datasets in the metabolic profiling of these diseases, in particular, the applications of these technologies to these diseases at the cellular, animal models, and human disease levels. In addition, we also extensively discuss the mechanisms linking the metabolic profiling in insulin resistance, T2DM, obesity, and atherosclerosis, with a particular emphasis on potential roles of increased production of reactive oxygen species (ROS) and mitochondria dysfunctions. PMID:24252331

  1. Childhood obesity affects adult metabolic syndrome and diabetes.

    PubMed

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

    2015-09-01

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

  2. B lymphocytes not required for progression from insulitis to diabetes in non-obese diabetic mice.

    PubMed

    Charlton, B; Zhang, M D; Slattery, R M

    2001-12-01

    Previous studies have implicated B lymphocytes in the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse. While it is clear that B lymphocytes are necessary, it has not been clear at which stage of disease they play a role; early, late or both. To clarify when B lymphocytes are needed, T lymphocytes were transferred from 5-week-old NOD female mice to age-matched NOD/severe combined immunodeficiency (SCID) recipient mice. NOD/SCID mice, which lack functionally mature T and B lymphocytes, do not normally develop insulitis or insulin-dependent diabetes melitus (IDDM). The NOD/SCID mice that received purified T lymphocytes from 5-week-old NOD mice subsequently developed insulitis and diabetes even though they did not have detectable B lymphocytes. This suggests that while B lymphocytes may be essential for an initial priming event they are not requisite for disease progression in the NOD mouse.

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

    PubMed

    Vlassara, Helen; Striker, Gary E

    2011-05-24

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

  4. TRP Channels as Therapeutic Targets in Diabetes and Obesity

    PubMed Central

    Zsombok, Andrea; Derbenev, Andrei V.

    2016-01-01

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

  5. 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

  6. 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.

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

    PubMed

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

    2016-01-01

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

  8. Insulin resistance is associated with gallstones even in non-obese, non-diabetic Korean men.

    PubMed

    Chang, Yoosoo; Sung, Eunju; Ryu, Seungho; Park, Yong-Woo; Jang, Yu Mi; Park, Minseon

    2008-08-01

    It remains unclear as to whether insulin resistance alone or in the presence of wellknown risk factors, such as diabetes or obesity, is associated with gallstones in men. The aim of this study was to determine whether insulin resistance is associated independently with gallstone disease in non-diabetic men, regardless of obesity. Study subjects were 19,503 Korean men, aged 30-69 yr, with fasting blood glucose level <126 mg/dL and without a documented history of diabetes. Gallbladder status was assessed via abdominal ultrasonography after overnight fast. Body mass index and waist circumference were measured. Insulin resistance was estimated by the Homeostasis Model Assessment of insulin resistance (HOMA-IR). The prevalence of obesity, abdominal obesity, and metabolic syndrome in the subjects with gallstones were higher than in those without. The prevalence of elevated HOMA (>75 percentile) in subjects with gallstones was significantly higher than in those without, and this association remained even after the obesity stratification was applied. In multiple logistic regression analyses, only age and HOMA proved to be independent predictors of gallstones. Insulin resistance was positively associated with gallstones in non-diabetic Korean men, and this occurred regardless of obesity. Gallstones appear to be a marker for insulin resistance, even in non-diabetic, nonobese men.

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

    PubMed

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

    2014-01-01

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

  10. Epigenetics in Adipose Tissue, Obesity, Weight Loss, and Diabetes12

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    1998-01-01

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

  12. 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...

  13. 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

  14. Dietary proteins in obesity and in diabetes.

    PubMed

    Keller, Ulrich

    2011-03-01

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

  15. Therapeutic phytogenic compounds for obesity and diabetes.

    PubMed

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

    2014-11-21

    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.

  16. Sugar intake, obesity, and diabetes in India.

    PubMed

    Gulati, Seema; Misra, Anoop

    2014-12-22

    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.

  17. 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

  18. Sleep, circadian dysrhythmia, obesity and diabetes

    PubMed Central

    Sridhar, Gumpeny Ramachandra; Sanjana, Narasimhadevara Santhi Nirmala

    2016-01-01

    Synchrony of biological processes with environmental cues developed over millennia to match growth, reproduction and senescence. This entails a complex interplay of genetic, metabolic, chemical, light, hormonal and hedonistic factors across life forms. Sleep is one of the most prominent rhythms where such a match is established. Over the past 100 years or so, it has been possible to disturb the synchrony between sleep-wake cycle and environmental cues. Development of electric lights, shift work and continual accessibility of the internet has disrupted this match. As a result, many non-communicable diseases such as obesity, insulin resistance, type 2 diabetes, coronary artery disease and malignancies have been attributed in part to such disruption. In this presentation a review is made of the origin and evolution of sleep studies, the pathogenic mediators for such asynchrony, clinical evidence and relevance and suggested management options to deal with the disturbances. PMID:27895820

  19. [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).

  20. 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

  1. 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

  2. Changes in diagnosed diabetes, obesity, and physical inactivity prevalence in US counties, 2004-2012

    PubMed Central

    Kirtland, Karen; Lin, Ji; Shrestha, Sundar; Thompson, Ted; Albright, Ann; Gregg, Edward W.

    2017-01-01

    Recent studies suggest that prevalence of diagnosed diabetes in the United States reached a plateau or slowed around 2008, and that this change coincided with obesity plateaus and increases in physical activity. However, national estimates can obscure important variations in geographic subgroups. We examine whether a slowing or leveling off in diagnosed diabetes, obesity, and leisure time physical inactivity prevalence is also evident across the 3143 counties of the United States. We used publicly available county estimates of the age-adjusted prevalence of diagnosed diabetes, obesity, and leisure-time physical inactivity, which were generated by the Centers for Disease Control and Prevention (CDC). Using a Bayesian multilevel regression that included random effects by county and year and applied cubic splines to smooth these estimates over time, we estimated the average annual percentage point change (APPC) from 2004 to 2008 and from 2008 to 2012 for diabetes, obesity, and physical inactivity prevalence in each county. Compared to 2004–2008, the median APPCs for diabetes, obesity, and physical inactivity were lower in 2008–2012 (diabetes APPC difference = 0.16, 95%CI 0.14, 0.18; obesity APPC difference = 0.65, 95%CI 0.59, 0.70; physical inactivity APPC difference = 0.43, 95%CI 0.37, 0.48). APPCs and APPC differences between time periods varied among counties and U.S. regions. Despite improvements, levels of these risk factors remained high with most counties merely slowing rather than reversing, which suggests that all counties would likely benefit from reductions in these risk factors. The diversity of trajectories in the prevalence of these risk factors across counties underscores the continued need to identify high risk areas and populations for preventive interventions. Awareness of how these factors are changing might assist local policy makers in targeting and tracking the impact of efforts to reduce diabetes, obesity and physical inactivity. PMID

  3. Changes in diagnosed diabetes, obesity, and physical inactivity prevalence in US counties, 2004-2012.

    PubMed

    Geiss, Linda S; Kirtland, Karen; Lin, Ji; Shrestha, Sundar; Thompson, Ted; Albright, Ann; Gregg, Edward W

    2017-01-01

    Recent studies suggest that prevalence of diagnosed diabetes in the United States reached a plateau or slowed around 2008, and that this change coincided with obesity plateaus and increases in physical activity. However, national estimates can obscure important variations in geographic subgroups. We examine whether a slowing or leveling off in diagnosed diabetes, obesity, and leisure time physical inactivity prevalence is also evident across the 3143 counties of the United States. We used publicly available county estimates of the age-adjusted prevalence of diagnosed diabetes, obesity, and leisure-time physical inactivity, which were generated by the Centers for Disease Control and Prevention (CDC). Using a Bayesian multilevel regression that included random effects by county and year and applied cubic splines to smooth these estimates over time, we estimated the average annual percentage point change (APPC) from 2004 to 2008 and from 2008 to 2012 for diabetes, obesity, and physical inactivity prevalence in each county. Compared to 2004-2008, the median APPCs for diabetes, obesity, and physical inactivity were lower in 2008-2012 (diabetes APPC difference = 0.16, 95%CI 0.14, 0.18; obesity APPC difference = 0.65, 95%CI 0.59, 0.70; physical inactivity APPC difference = 0.43, 95%CI 0.37, 0.48). APPCs and APPC differences between time periods varied among counties and U.S. regions. Despite improvements, levels of these risk factors remained high with most counties merely slowing rather than reversing, which suggests that all counties would likely benefit from reductions in these risk factors. The diversity of trajectories in the prevalence of these risk factors across counties underscores the continued need to identify high risk areas and populations for preventive interventions. Awareness of how these factors are changing might assist local policy makers in targeting and tracking the impact of efforts to reduce diabetes, obesity and physical inactivity.

  4. 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...

  5. Obesity and aging: determinants of endothelial cell dysfunction and atherosclerosis.

    PubMed

    Barton, Matthias

    2010-10-01

    Endothelial cells are both the source and target of factors contributing to atherosclerosis. After the discovery of the endothelium-derived relaxing factor (EDRF) by Robert F. Furchgott in 1980 it soon became clear that endothelial cells also release vasoactive factors distinct from nitric oxide (NO) namely, endothelium-derived contracting factors (EDCF) as well as hyperpolarizing factors (EDHF). Vasoactive factors derived from endothelial cells include NO/EDRF, reactive oxygen species, endothelins and angiotensins which have either EDRF or EDCF functions, cyclooxygenase-derived EDCFs and EDRFs, and EDHFs. Endothelial factors are formed by enzymes such as NO synthase, cyclooxygenase, converting enyzmes, NADPH oxidases, and epoxigenases, among others, and participate in the regulation of vascular homeostasis under physiological conditions; however, their abnormal regulation due to endothelial cell dysfunction contributes to disease processes such as atherosclerosis, arterial hypertension, and renal disease. Because of recent changes in world demographics and the declining health status of the world's population, both aging and obesity as independent risk factors for atherosclerosis-related diseases such as coronary artery disease and stroke, will continue to increase in the years to come. Obesity and associated conditions such as arterial hypertension and diabetes are now also some of the primary health concerns among children and adolescents. The similarities of pathomechanisms activated in obesity and aging suggest that obesity--at least in the vasculature--can be considered to have effects consistent with accelerated, "premature" aging. Pathomechanisms as well as the clinical issues of obesity- and aging-associated vascular changes important for atherosclerosis development and prevention are discussed.

  6. Obesity, age, ethnicity, and clinical features of prostate cancer patients

    PubMed Central

    Wu, Victor J; Pang, Darren; Tang, Wendell W; Zhang, Xin; Li, Li; You, Zongbing

    2017-01-01

    Approximately 36.5% of the U.S. adults (≥ 20 years old) are obese. Obesity has been associated with type 2 diabetes mellitus, cardiovascular disease, stroke, and several types of cancer. The present study included 1788 prostate cancer patients who were treated with radical prostatectomy at the Ochsner Health System, New Orleans, Louisiana, from January, 2001 to March, 2016. The patient’s medical records were retrospectively reviewed. Body mass index (BMI), age, ethnicity (Caucasians versus African Americans), clinical stage, Gleason score, and prostate-specific antigen (PSA) levels were retrieved. The relative risk of the patients was stratified into low risk and high risk groups. Associative analyses found that BMI was associated with age, clinical stage, Gleason score, but not ethnicity, PSA levels, or the relative risk in this cohort. Age was associated with ethnicity, clinical stage, Gleason score, and PSA levels, as well as the relative risk. Ethnicity was associated with Gleason score and PSA levels as well as the relative risk, but not clinical stage. These findings suggest that obesity is associated with advanced prostate cancer with stage T3 or Gleason score ≥ 7 diseases, and age and ethnicity are important factors that are associated with the clinical features of prostate cancer patients. PMID:28337464

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

    PubMed

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

    2015-12-01

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

  8. 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

  9. Work, Diabetes and Obesity: A Seven Year Follow-Up Study among Danish Health Care Workers

    PubMed Central

    Poulsen, Kjeld; Cleal, Bryan; Clausen, Thomas; Andersen, Lars L.

    2014-01-01

    Objectives The rise in prevalence of diabetes is alarming and research ascribes most of the increase to lifestyle. However, little knowledge exists about the influence of occupational factors on the risk for developing diabetes. This study estimates the importance of work and lifestyle as risk factors for developing diabetes mellitus among healthcare workers and explores the association of work factors and obesity, which is a risk factor for diabetes. Methods Questionnaire-based prospective cohort study among 7,305 health care workers followed for seven years in the Danish National Diabetes Register. We used bivariate comparisons to give an unadjusted estimate of associations, followed by adjusted survival analysis and logistic regression models to estimate the influences of potential risk factors related to job, health and lifestyle on diabetes and obesity. Results During seven years of follow up, 3.5% of participants developed diabetes, associated with obesity (HR  =  6.53; 95% CI 4.68–9.10), overweight (HR  =  2.89; CI 2.11–3.96) age 50–69 y (HR  =  2.27; 95% CI 1.57–3.43) and high quality of leadership (HR  =  1.60; CI 1.19–2.16). Obesity at baseline was most common among the youngest employees, and was mainly associated with developing diabetes (OR  =  3.84; CI 2.85–5.17), impaired physical capacity and physical inactivity. In the occupational setting, obesity was associated with shift work, severe musculoskeletal pain, low influence, but also by good management, fewer role conflicts and a positive work-life balance. Looking only at non-smokers, removed the influence of age and pain. However, non-smokers also had higher depression scores and more role conflicts. Conclusions Confirming obesity as the strongest risk factor for developing diabetes, the present study identified few occupational risk factors. However, obesity, the key risk factor for diabetes, had a more variable relation with work than did diabetes. PMID:25068830

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

    PubMed

    Miyata, Yugo; Shimomura, Iichiro

    2016-03-01

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

  11. 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...

  12. Transcriptomic analysis of visceral adipose from healthy and diabetic obese subjects

    PubMed Central

    Mathur, Sandeep Kumar; Jain, Priyanka; Mathur, Prashant; Punjabi, Poonam; Agarwal, Atima; Sharma, Abhay

    2013-01-01

    Understanding the role of visceral fat accumulation in the occurrence and progression of metabolic syndrome is of considerable interest. In order to understand the difference between visceral tissue biology of healthy and unhealthy obese individuals, we have used microarray profiling to compare genome-wide expression differences between visceral adipose tissue biopsies obtained from obese diabetics, and those from age and body mass index (BMI) matched normal glucose tolerance subjects. Whereas genes upregulated in diabetics showed enrichment of natural killer cell mediated cytotoxicity, the downregulated genes showed enrichment of biosynthesis of unsaturated fatty acids. Given the known inhibitory effect of unsaturated fatty acids on inflammation and natural killer cell number or activity, our results suggest that visceral inflammation resulting from decreased levels of unsaturated fatty acids may underlie progression of diabetes in obese individuals. PMID:23869300

  13. 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.

  14. Effect of the Obesity Epidemic on Kidney Transplantation: Obesity Is Independent of Diabetes as a Risk Factor for Adverse Renal Transplant Outcomes

    PubMed Central

    Kwan, Jennifer M.; Hajjiri, Zahraa; Metwally, Ahmed

    2016-01-01

    Background Obesity is a growing epidemic in most developed countries including the United States resulting in an increased number of obese patients with end-stage renal disease. A previous study has shown that obese patients with end-stage renal disease have a survival benefit with transplantation compared with dialysis. However, due to serious comorbidities, many centers place restrictions on the selection of obese patients for transplantation. Further, due to obese patients having an increased risk of diabetes, it is unclear whether obesity can be an independent risk, independent of diabetes for increasing adverse renal transplant outcomes. Methods To investigate the role of obesity in kidney transplantation, we used the Scientific Registry of Transplant Recipients database. After filtering for subjects that had the full set of covariates including age, gender, graft type, ethnicity, diabetes, peripheral vascular disease, dialysis time and time period of transplantation for our analysis, 191,091 subjects were included in the analyses. Using multivariate logistic regression analyses adjusted for covariates we determined whether obesity is an independent risk factor for adverse outcomes such as delayed graft function, acute rejection, urine protein and graft failure. Cox regression modeling was used to determine hazard ratios of graft failure. Results Using multivariate model analyses, we found that obese patients have significantly increased risk of adverse transplant outcomes, including delayed graft function, graft failure, urine protein and acute rejection. Cox regression modeling hazard ratios showed that obesity also increased risk of graft failure. Life-table survival curves showed that obesity may be a risk factor independent of diabetes mellitus for a shorter time to graft failure. Conclusions A key observation in our study is that the risks for adverse outcome of obesity are progressive with increasing body mass index. Furthermore, pre-obese overweight

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

    PubMed

    Astrup, A

    2001-04-01

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

  16. Salivary inflammatory markers and microbiome in normoglycemic lean and obese children compared to obese children with type 2 diabetes

    PubMed Central

    Sabharwal, Amarpeet; Tsompana, Maria; Berman, Harvey A.; Haase, Elaine M.; Miecznikowski, Jeffrey C.

    2017-01-01

    Background There is emerging evidence linking diabetes with periodontal disease. Diabetes is a well-recognized risk factor for periodontal disease. Conversely, pro-inflammatory molecules released by periodontally-diseased tissues may enter the circulation to induce insulin resistance. While this association has been demonstrated in adults, there is little information regarding periodontal status in obese children with and without type 2 diabetes (T2D). We hypothesized that children with T2D have higher rates of gingivitis, elevated salivary inflammatory markers, and an altered salivary microbiome compared to children without T2D. Methods Three pediatric cohorts ages 10–19 years were studied: lean (normal weight—C), obese (Ob), and obese with T2D (T2D). Each subject completed an oral health survey, received a clinical oral examination, and provided unstimulated saliva for measurement of inflammatory markers and microbiome analysis. Results The diabetes group was less likely to have had a dental visit within the last six months. Body mass index (BMI) Z-scores and waist circumference/height ratios were similar between Ob and T2D cohorts. The number of carious lesions and fillings were similar for all three groups. The gingival index was greater in the T2D group compared to the Ob and C groups. Although salivary microbial diversity was minimal between groups, a few differences in bacterial genus composition were noted. Conclusions Obese children with T2D show a trend toward poorer oral health compared to normal weight and obese children without T2D. This study characterizes the salivary microbiome of children with and without obesity and T2D. This study supports a modest link between T2D and periodontal inflammation in the pediatric population. PMID:28253297

  17. Obesity, insulin resistance and diabetes--a worldwide epidemic.

    PubMed

    Seidell, J C

    2000-03-01

    Obesity is now commonly defined in adults as a BMI > 30 kg/m2. The prevalence of obesity in established market economies (Europe, USA, Canada, Australia, etc.) varies greatly, but a weighed estimate suggests an average prevalence in the order of 15-20%. The prevalence in these countries generally shows increasing trends over time. Obesity is also relatively common in Latin America, but much less so in sub-Saharan Africa and Asia where the majority of the world population lives. Nevertheless obesity rates are increasing there as well and, more importantly, rates of diabetes are increasing even more quickly, particularly in Asian countries. The risks of type 2 diabetes mellitus in these countries tend to increase sharply at levels of BMI generally classified as acceptable in European and North American white people. There have been suggestions to adopt specific classifications of obesity in Asians (e.g. BMI 23 for overweight and 25 or 27 kg/m2 for obesity) and this will greatly affect the prevalence estimates of obesity worldwide (currently at about 250 million people). Particularly for health promotion purposes BMI may be replaced by a classification based on waist circumference, but also specific classifications for different ethnic groups may be necessary. The number of diabetics has been projected to increase from 135 million in 1995 to 300 million in 2025. Much of this increase will be seen in Asia. In summary, both obesity and type 2 diabetes are common consequences of changing lifestyles (increased sedentary lifestyles and increased energy density of diets). Both are potentially preventable through lifestyle modification on a population level, but this requires a coherent and multifaceted strategy. Such strategies are not developed or implemented. These developments point toward the great urgency to develop global and national plans for adequate prevention and management of obesity and type 2 diabetes mellitus.

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

    PubMed

    Temelkova-Kurktschiev, T; Stefanov, T

    2012-01-01

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

  19. 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

  20. Obesity accelerates epigenetic aging of human liver.

    PubMed

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

    2014-10-28

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

  1. 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

  2. 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.

  3. MicroRNAs and type 2 diabetes/obesity.

    PubMed

    Dehwah, Mustafa Abdo Saif; Xu, Aimin; Huang, Qingyang

    2012-01-01

    MicroRNAs belong to a newly identified class of small non-coding RNAs that have been widely implicated in the fine-tuning of many physiological processes such as the pathogenesis of type 2 diabetes (T2D) and obesity. Microarray studies have highlighted an altered profile of miRNA expression in insulin target tissues in diabetic and obese models. Emerging evidences suggest that miRNAs play significant roles in insulin production, secretion and actions, as well as in diverse aspects of glucose homeostasis and adipocyte differentiation. The identification of tissue-specific miRNAs implicated in T2D and obesity might be useful for the future development of effective strategies for early diagnosis and therapeutic intervention of obesity-related medical complications.

  4. 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

  5. Obesity & Diabetes: An experience at a public sector tertiary care hospital

    PubMed Central

    Ali, Zeeshan; Ahmed, Syed Masroor; Nageen, Ayesha; Tanveer Alam, Muhammad; Sohrab, Shabnam

    2014-01-01

    Objective: To detect the frequency of Obesity in type 2 diabetic patients. Methods: It was a Cross Sectional study carried out at Diabetes Clinic, Medical Unit III, Jinnah Postgraduate Medical Centre Karachi from 1st Jan 2012 to 30th June 2012. Three hundred and eighty seven (387) type II diabetic patients of either sex and any age were included in the study. Non-purposive convenience sampling technique was used to enroll patients in the study. History regarding diabetes, hypertension (HTN), Cerebrovascular Accidents (CVA), smoking and other tobacco exposure was taken. Physical examination was carried out and height, weight, body mass index (BMI), blood pressure, peripheral pulses and ankle-brachial index (ABI) was calculated. Categorical variables such as Gender, Age groups, BMI groups, HTN, smoking, hyperlipidemia and ABI were expressed as frequencies and proportions. Means with standard deviations were calculated for continuous variables such as age, duration of diabetes, BMI, duration of HTN and duration dyslipidemia. For categorical variables, differences between patients were tested using the chi-square test. P value of ≤ 0.05 was considered significant. Results: Males were 128 in number (33%) and female were 259 in number (67%). Mean age was 52 yrs (+/- 9.67) and the mean duration of diabetes was 9.36 yrs (+/- 6.39). Hypertension was seen in 210 people (54%). 49(12.7%) were smokers and 39(10%) chewed tobacco. Normal BMI was seen in 62 patients (16%), 44 (11.4%) were overweight and 281(72.6%) was obese. Obesity was much more prevalent amongst the female gender that is 208(80%) versus male which was 73 (57%) and this was statistically significant (p-value 0.001). Hypertension was also more prevalent in obese patients and was statistically significant (p-value 0.04). Statistically significant lower mean BMI was found in smokers, tobacco chewers and/or had exposure to tobacco (0.001, 0.04, and 0.001 respectively). Conclusion: The study shows that there is a

  6. Prediabetes, undiagnosed diabetes, and diabetes among Mexican adults: findings from the Mexican Health and Aging Study

    PubMed Central

    Kumar, Amit; Wong, Rebeca; Ottenbacher, Kenneth J.; Al Snih, Soham

    2016-01-01

    Purpose The purpose of the study was to examine the prevalence and determinants of prediabetes, undiagnosed diabetes, and diabetes among Mexican adults from a subsample of the Mexican Health and Aging Study. Methods We examined 2012 participants from a subsample of the Mexican Health and Aging Study. Measures included sociodemographic characteristics, body mass index, central obesity, medical conditions, cholesterol, high-density lipoprotein cholesterol, hemoglobin A1c, and vitamin D. Logistic regression was performed to identify factors associated with prediabetes, undiagnosed diabetes, and self-reported diabetes. Results Prevalence of prediabetes, undiagnosed, and self-reported diabetes in this cohort was 44.2%, 18.0%, and 21.4%, respectively. Participants with high waist-hip ratio (1.61, 95% confidence interval [CI] = 1.05–2.45) and high cholesterol (1.85, 95% CI = 1.36–2.51) had higher odds of prediabetes. Overweight (1.68, 95% CI = 1.07–2.64), obesity (2.38, 95% CI = 1.41–4.02), and high waist circumference (1.60, 95% CI = 1.06–2.40) were significantly associated with higher odds of having undiagnosed diabetes. Those residing in a Mexican state with high U.S. migration had lower odds of prediabetes (0.61, 95% CI = 0.45–0.82) and undiagnosed diabetes (0.53, 95% CI = 0.41–0.70). Those engaged in regular physical activity had lower odds of undiagnosed diabetes (0.74, 95% CI = 0.57–0.97). Conclusions There is a high prevalence of prediabetes and undiagnosed diabetes among Mexican adults in this subsample. Findings suggest the need for resources to prevent, identify, and treat persons with prediabetes and undiagnosed diabetes. PMID:26872919

  7. 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.

  8. 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.

  9. Impact of bariatric surgery on life expectancy in severely obese patients with diabetes: A Decision analysis

    PubMed Central

    Schauer, Daniel P.; Arterburn, David E.; Livingston, Edward H.; Coleman, Karen J.; Sidney, Steve; Fisher, David; O'Connor, Patrick; Fischer, David; Eckman, Mark H.

    2014-01-01

    Objective To create a decision analytic model to estimate the balance between treatment risks and benefits for severely obese patients with diabetes. Summary Background Data Bariatric surgery leads to many desirable metabolic changes, but long-term impact of bariatric surgery on life expectancy in patients with diabetes has not yet been quantified. Methods We developed a Markov state transition model with multiple Cox proportional hazards models and logistic regression models as inputs to compare bariatric surgery versus no surgical treatment for severely obese diabetic patients. The model is informed by data from three large cohorts: 1) 159,000 severely obese diabetic patients (4,185 had bariatric surgery) from 3 HMO Research Network sites, 2) 23,000 subjects from the Nationwide Inpatient Sample (NIS), and 3) 18,000 subjects from the National Health Interview Survey linked to the National Death Index. Results In our main analyses, we found that a 45 year-old female with diabetes and a BMI of 45 kg/m2 gained an additional 6.7 years of life expectancy with bariatric surgery (38.4 years with surgery vs. 31.7 without). Sensitivity analyses revealed that the gain in life expectancy decreased with increasing BMI, until a BMI of 62 kg/m2 is reached, at which point nonsurgical treatment was associated with greater life expectancy. Similar results were seen for both men and women in all age groups. Conclusions For most severely obese patients with diabetes, bariatric surgery appears to improve life expectancy; however, surgery may reduce life expectancy for the super obese with BMIs over 62 kg/m2. PMID:25844968

  10. 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

  11. 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.

  12. Obesity and diabetes genetic variants associated with gestational weight gain

    PubMed Central

    Stuebe, Alison M.; Lyon, Helen; Herring, Amy; Ghosh, Joyee; Wise, Alison; North, Kari E.; Siega-Riz, Anna Maria

    2011-01-01

    Objective To determine whether genetic variants associated with diabetes and obesity predict gestational weight gain. Study Design 960 participants in the Pregnancy, Infection and Nutrition cohorts were genotyped for 27 single-nucleotide polymorphisms (SNPs) associated with diabetes and obesity. Results Among white and black women (n=960), KCNQ1 risk allele carriage was directly associated with weight gain (p < 0.01). In Bayesian hierarchical models among white women (N=628), we found posterior odds ratios > 3 for inclusion of TCF2 and THADA SNPs in our models. Among black women (n=332), we found associations between risk allele carriage and weight gain for the THADA and INSIG2 SNPs. In Bayesian variable selection models, we found an interaction between the TSPAN8 risk allele and pre-gravid obesity, with lower weight gain among obese risk allele carriers. Conclusion We found evidence that diabetes and obesity risk alleles interact with maternal pre-gravid BMI to predict gestational weight gain. PMID:20816152

  13. 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...

  14. Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?

    PubMed

    Klil-Drori, Adi J; Azoulay, Laurent; Pollak, Michael N

    2017-02-01

    The prevalence of obesity, of type 2 diabetes mellitus (T2DM), and of cancer are all increasing globally. The relationships between these diseases are complex, and thus difficult to elucidate; nevertheless, evidence supports the hypothesis that obesity increases the risks of both T2DM and certain cancers. Further complexity arises from controversial evidence that specific drugs used in the treatment of T2DM increase or decrease cancer risk or influence cancer prognosis. Herein, we review the current evidence from studies that have addressed these relationships, and summarize the methodological challenges that are frequently encountered in such research. We also outline the physiology that links obesity, T2DM, and neoplasia. Finally, we outline the practical principles relevant to the increasingly common challenge of managing patients who have been diagnosed with both diabetes and cancer.

  15. 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

  16. 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.

  17. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity

    PubMed Central

    Fu, Zhiyao; Berhane, Feven; Fite, Alemu; Seyoum, Berhane; Abou-Samra, Abdul B.; Zhang, Ren

    2014-01-01

    Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly discovered circulating factor that regulates lipid metabolism and promotes pancreatic β-cell proliferation. Whether circulating levels of lipasin in humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial state, however, is unknown. The current study aimed to compare serum lipasin levels in those who were a) non-diabetic (N = 15) or diabetic (BMI- and age-matched; N = 14); b) lean or obese (N = 53 totally) and c) fasting and 2 hours following a defined meal (N = 12). Serum lipasin levels were determined by the enzyme-linked immunosorbent assay. Lipasin levels [mean ± SEM] were increased by more than two fold (P < 0.001) in the diabetic patients (5.56 ± 0.73 ng/mL) as compared to the control subjects (2.19 ± 0.24 ng/mL). Serum lipasin levels were positively correlated with BMI (rho = 0.49, P < 0.001), and showed a 35% increase 2 hours following a defined meal (P = 0.009). Therefore, lipasin/betatrophin is nutritionally-regulated hepatokine that is increased in human type 2 diabetes and obesity. PMID:24852694

  18. Empowerment in the Treatment of Diabetes and Obesity

    PubMed Central

    2016-01-01

    As the available therapies for diabetes and obesity are not effective enough, diabetologists and educators search for new methods to collaborate with patients in order to support their health behaviors. The aim of this review is to discuss perspectives for the development of new empowerment-type therapies in the treatment of diabetes/obesity. Empowerment is a process whereby patients gain the necessary knowledge to influence their own behavior to improve the quality of their lives. It is carried out in five stages: (1) identify the problem, (2) explain the feelings and meanings, (3) build a plan, (4) act, and (5) experience and assess the execution. Although many years have passed since the advent and popularization of the concept of empowerment, the area remains controversial, mainly with regard to the methodology of therapy. Some previous studies have confirmed the positive effect of empowerment on body weight, metabolic control, and quality of life of patients with type 2 diabetes; however, few studies have been conducted in patients with type 1 diabetes. There is still a need to confirm the effectiveness of empowerment in accordance with Evidence Based Medicine by performing long-term observational studies in a large group of patients. In future, empowerment may become part of the standard of care for patients with diabetes and/or obesity. PMID:28090541

  19. Fermented garlic protects diabetic, obese mice when fed a high-fat diet by antioxidant effects.

    PubMed

    Jung, Young-Mi; Lee, Seon-Ha; Lee, Dong-Sub; You, Myung-Jin; Chung, In Kwon; Cheon, Woo Hyun; Kwon, Young-Sam; Lee, Young-Joon; Ku, Sae-Kwang

    2011-05-01

    This study examined the bioactivity of yeast (Saccharomyces cerevisiae)-fermented aged black garlic (FBG) on obese mice supplied a high-fat diet (HFD) and its in vitro antioxidant activity. Aged black garlic (BG) exhibits potent antioxidative effects and has been subjected to extensive research. In addition, the bioactivity of some natural products is increased by fermentation. In a preliminary test, this study found that the antioxidant activity of FBG is stronger than that of BG. Therefore, it was hypothesized that the bioactivity of BG would be increased by yeast fermentation and would be a good candidate as a nutraceutical product for improving the oxidative defense systems in older patients or patients affected by various oxidative stresses, for example, diabetes and diabetic complications. To test this hypothesis, the bioactivities of FBG in diabetic and obese mice as well as the antioxidant activity in vitro were examined. After 91 days of continuous HFD supply, the mice showed marked obesity, hyperglycemia, hyperlipemia, and liver and kidney damages. Black garlic and all 3 different doses of FBG showed favorable hepatoprotective, nephroprotective, hypolipidemic, and antiobesity effects compared with the HFD control, but no hypoglycemic effects. In particular, more favorable bioactivity against all 4 HFD-induced diabetic complications was detected in the FBG-treated groups compared with the group given equivalent doses of BG. These findings suggest that the bioactivities of BG can be improved by yeast fermentation.

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

    PubMed

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

    2015-01-01

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

  1. 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

  2. Obesity in the Context of Aging: Quality of Life Considerations.

    PubMed

    Corica, Francesco; Bianchi, Giampaolo; Corsonello, Andrea; Mazzella, Natalia; Lattanzio, Fabrizia; Marchesini, Giulio

    2015-07-01

    The progressive increase in the prevalence of obesity and aging in the population is resulting in increased healthcare and disability spending. The burden of obesity is particularly relevant in old age, due to accumulating co-morbidities and changes in body composition. Sarcopenic obesity, a mix of over- and under-nutrition, causes frailty, disability, and problems in social and psychological areas, impacting overall health-related quality of life (HR-QOL). The relationship between obesity, aging, and HR-QOL is, however, much more complex than generally acknowledged and is difficult to disentangle. The impact of obesity on HR-QOL is particularly strong in young people, who are free of co-morbidities. It progressively attenuates, compared with the general population, with advancing age, when co-morbid conditions are diffusely present and reduce the perceived health status, independent of obesity. However, even this apparent 'obesity paradox' should not minimize the importance of obesity on HR-QOL, as other obesity-associated limitations and disabilities do impact HR-QOL in older age. A patient-centered approach aimed at reducing the disability and social isolation of advancing age is mandatory to improve HR-QOL in any class of obesity.

  3. Evaluation of antidiabetic activity of polysaccharide isolated from Phellinus linteus in non-obese diabetic mouse.

    PubMed

    Kim, Hwan Mook; Kang, Jong Soon; Kim, Jee Youn; Park, Song-Kyu; Kim, Hyung Sook; Lee, Young June; Yun, Jieun; Hong, Jin Tae; Kim, Youngsoo; Han, Sang-Bae

    2010-01-01

    Polysaccharide (PLP) isolated from Phellinus linteus inhibits tumor growth and metastasis by enhancing immune functions of macrophages, dendritic cells, NK cells, T cells, and B cells. Here, we report that PLP can inhibit the development of autoimmune diabetes in non-obese diabetic (NOD) mice. Although 80% of the NOD mice had developed diabetes by 24 weeks of age, none of the PLP-treated NOD mice developed diabetes. The mean blood glucose levels were 110mg/dl in PLP-treated mice and 499mg/dl in control NOD mice. Histological examination of the pancreatic islets revealed that most of the islets isolated from PLP-treated mice were less infiltrated with lymphocytes compared with those of control mice. Spleen cells from diabetic NOD mice could adaptively transfer diabetes into NOD/SCID mice, but those from PLP-treated NOD mice showed delayed transfer of diabetes. PLP inhibited the expression of inflammatory cytokines, including IFN-gamma, IL-2, and TNF-alpha by Th1 cells and macrophages, but up-regulated IL-4 expression by Th2 cells in NOD mice. PLP did not prevent streptozotocin-induced diabetic development in ICR mice. Taken together, these results suggest that PLP inhibits the development of autoimmune diabetes by regulating cytokine expression.

  4. Oxidative stress and susceptibility to mitochondrial permeability transition precedes the onset of diabetes in autoimmune non-obese diabetic mice.

    PubMed

    Malaguti, C; La Guardia, P G; Leite, A C R; Oliveira, D N; de Lima Zollner, R L; Catharino, R R; Vercesi, A E; Oliveira, H C F

    2014-12-01

    Beta cell destruction in type 1 diabetes (TID) is associated with cellular oxidative stress and mitochondrial pathway of cell death. The aim of this study was to determine whether oxidative stress and mitochondrial dysfunction are present in T1D model (non-obese diabetic mouse, NOD) and if they are related to the stages of disease development. NOD mice were studied at three stages: non-diabetic, pre-diabetic, and diabetic and compared with age-matched Balb/c mice. Mitochondria respiration rates measured at phosphorylating and resting states in liver and soleus biopsies and in isolated liver mitochondria were similar in NOD and Balb/c mice at the three disease stages. However, NOD liver mitochondria were more susceptible to calcium-induced mitochondrial permeability transition as determined by cyclosporine-A-sensitive swelling and by decreased calcium retention capacity in all three stages of diabetes development. Mitochondria H2O2 production rate was higher in non-diabetic, but unaltered in pre-diabetic and diabetic NOD mice. The global cell reactive oxygen species (ROS), but not specific mitochondria ROS production, was significantly increased in NOD lymphomononuclear and stem cells in all disease stages. In addition, marked elevated rates of 2',7'-dichlorodihydrofluorescein (H2DCF) oxidation were observed in pancreatic islets from non-diabetic NOD mice. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and lipidomic approach, we identified oxidized lipid markers in NOD liver mitochondria for each disease stage, most of them being derivatives of diacylglycerols and phospholipids. These results suggest that the cellular oxidative stress precedes the establishment of diabetes and may be the cause of mitochondrial dysfunction that is involved in beta cell death.

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

    PubMed Central

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

    2015-01-01

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

  6. Obesity and Hyperlipidemia are Risk Factors for Early Diabetic Neuropathy

    PubMed Central

    Smith, A. Gordon; Singleton, J. Robinson

    2013-01-01

    The Utah Diabetic Neuropathy Study (UDNS) examined 218 type 2 diabetic subjects without neuropathy symptoms, or with symptoms of < 5 years, in order to evaluate risk factors for neuropathy development. Each subject completed symptom questionnaires, the Utah Early Neuropathy Scale (UENS), nerve conduction studies (NCS), quantitative sensory testing (QST) for vibration and cold detection, quantitative sudomotor axon reflex testing (QSART), and skin biopsy with measurement of intraepidermal nerve fiber density (IENFD). Those with abnormalities of ≥ 3 were classified as having probable, and those with 1–2 as possible neuropathy. The relationship between glycemic control, lipid parameters (high density lipoprotein and triglyceride levels), blood pressure, and obesity, and neuropathy risk was examined. There was a significant relationship between the number of abnormalities among these features and neuropathy status (p<0.01). Hypertriglyceridemia, obesity and 3 or more abnormalities increased neuropathy risk (risk ratios 2.1 p<0.03, 2.9 p>0.02 and 3.0 p<0.004 respectively). Multivariate analysis found obesity and triglycerides were related to loss of small unmyelinated axons based on IENFD whereas elevated hemoglobin A1c was related to large myelinated fiber loss (motor conduction velocity). These findings indicate obesity and hypertriglyceridemia significantly increase risk for peripheral neuropathy, independent of glucose control. Obesity/hypertriglyceridemia and hyperglycemia may have differential effects on small versus large fibers. PMID:23731827

  7. Obesity and hyperlipidemia are risk factors for early diabetic neuropathy.

    PubMed

    Smith, A Gordon; Singleton, J Robinson

    2013-01-01

    The Utah Diabetic Neuropathy Study (UDNS) examined 218 type 2 diabetic subjects without neuropathy symptoms, or with symptoms of<5 years, in order to evaluate risk factors for neuropathy development. Each subject completed symptom questionnaires, the Utah Early Neuropathy Scale (UENS), nerve conduction studies (NCS), quantitative sensory testing (QST) for vibration and cold detection, quantitative sudomotor axon reflex testing (QSART), and skin biopsy with measurement of intraepidermal nerve fiber density (IENFD). Those with abnormalities of≥3 were classified as having probable, and those with 1-2 as possible neuropathy. The relationship between glycemic control, lipid parameters (high density lipoprotein and triglyceride levels), blood pressure, and obesity, and neuropathy risk was examined. There was a significant relationship between the number of abnormalities among these features and neuropathy status (p<0.01). Hypertriglyceridemia, obesity and 3 or more abnormalities increased neuropathy risk (risk ratios 2.1 p<0.03, 2.9 p>0.02 and 3.0 p<0.004 respectively). Multivariate analysis found obesity and triglycerides were related to loss of small unmyelinated axons based on IENFD whereas elevated hemoglobin A1c was related to large myelinated fiber loss (motor conduction velocity). These findings indicate obesity and hypertriglyceridemia significantly increase risk for peripheral neuropathy, independent of glucose control. Obesity/hypertriglyceridemia and hyperglycemia may have differential effects on small versus large fibers.

  8. 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

  9. 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.

  10. 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

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

    PubMed

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

    2016-01-01

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

  12. 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

  13. Baroreflex sensitivity in children and adolescents: physiology, hypertension, obesity, diabetes mellitus.

    PubMed

    Honzíková, N; Závodná, E

    2016-12-13

    The increased prevalence of obesity in children and its complications have led to a greater interest in studying baroreflex sensitivity (BRS) in children. This review of BRS in children and adolescents includes subtopics on: 1. Resting values of BRS and their reproducibility, 2. Genetics of BRS, 3. The role of a primarily low BRS and obesity in the development of hypertension, and 4. Association of diabetes mellitus, BRS, and obesity. The conclusions specific to this age follow from this review: 1. The mean heart rate (HR) influences the measurement of BRS. Since the mean HR decreases during adolescence, HR should be taken into account. 2. A genetic dependency of BRS was found. 3. Low BRS values may precede pathological blood-pressure elevation in children with white-coat hypertension. We hypothesize that low BRS plays an active role in the emergence of hypertension in youth. A contribution of obesity to the development of hypertension was also found. We hypothesize that both factors, a primarily low BRS and obesity, are partially independent risk factors for hypertension in youths. 4. In diabetics, a low BRS compared to healthy children can be associated with insulin resistance. A reversibility of the BRS values could be possible after weight loss.

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

    PubMed

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

    2015-12-01

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

  15. Obesity, diabetes, hypertension, and vegetarian status among Seventh-Day Adventists in Barbados: preliminary results.

    PubMed

    Brathwaite, Noel; Fraser, Henry S; Modeste, Naomi; Broome, Hedy; King, Rosaline

    2003-01-01

    A population-based sample of Seventh-Day Adventists was studied to determine the relationship between vegetarian status, body mass index (BMI), obesity, diabetes mellitus (DM), and hypertension, in order to gain a better understanding of factors influencing chronic diseases in Barbados. A systematic sampling from a random start technique was used to select participants for the study. A standard questionnaire was used to collect data on demographic and lifestyle characteristics, to record anthropometrics and blood pressure measurements, and to ascertain the hypertension and diabetes status of participants. The sample population consisted of 407 Barbadian Seventh-Day Adventists (SDAs), who ranged in age from 25 to 74 years. One hundred fifty-three (37.6%) participants were male, and 254 (62.4%) were female, and 43.5% were vegetarians. The prevalence rates of diabetes and hypertension were lower among long-term vegetarians, compared to non-vegetarians, and long-term vegetarians were, on average, leaner than non-vegetarians within the same cohort. A significant association was observed between a vegetarian diet and obesity (vegetarian by definition P=.04, self-reported vegetarian P=.009) in this population. Other components of the study population lifestyle should be further analyzed to determine the roles they may plan in lessening the prevalence rates of obesity, diabetes, and hypertension.

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

    PubMed

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

    2001-01-01

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

  17. Insulinotropic effects of GPR120 agonists are altered in obese diabetic and obese non-diabetic states.

    PubMed

    Zhang, Dan; So, Wing Yan; Wang, Yi; Wu, Shang Ying; Cheng, Qianni; Leung, Po Sing

    2017-02-01

    G-protein-coupled receptor 120 (GPR120) is a putative target for obesity and diabetes therapies. However, it remains controversial whether resident GPR120 plays a direct regulatory role in islet β-cell insulin secretion. The present study examined this issue in isolated rodent islets and rat β-cell line INS-1E, and assessed the role of GPR120 in islet insulin secretion in obese non-diabetic (OND) and diabetic states. GPR120 expression was detected in rodent islet β-cells. Docosahexaenoic acid (DHA) and synthetic GPR120 agonist GSK137647 (GSK) augmented insulin release from rat/mouse islets and INS-1E; DHA effects were partially mediated by GPR40. GPR120 knockdown and overexpression attenuated and enhanced DHA effects in INS-1E respectively. DHA and GSK improved postprandial hyperglycaemia of diabetic mice. Inhibition of calcium signalling in INS-1E reduced GPR120 activation-induced insulinotropic effects. The insulinotropic effects of DHA/GSK were amplified in OND rat islets, but diminished in diabetic rat islets. GPR120 and peroxisome proliferator-activated receptor γ (PPARγ) expression were elevated in OND islets and palmitic acid (PA)-treated INS-1E, but reduced in diabetic islets and high glucose-treated INS-1E. PPARγ activation increased GPR120 expression in rat islets and INS-1E. DHA and GSK induced protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) phosphorylation in rodent islets and INS-1E, and these effects were altered in OND and diabetic states. Taken together, the present study indicates that (i) GPR120 activation has an insulinotropic influence on β-cells with the involvement of calcium signalling; (ii) GPR120 expression in β-cells and GPR120-mediated insulinotropic effects are altered in OND and diabetic states in distinct ways, and these alterations may be mediated by PPARγ.

  18. Association between race, obesity and diabetes in elderly community dwellers: data from the FIBRA study.

    PubMed

    Moretto, Maria Clara; Fontaine, Anne Marie; Garcia, Cássia de Almeida Merlo Sarzedo; Neri, Anita Liberalesso; Guariento, Maria Elena

    2016-11-03

    This study sought to investigate the effect of race on measures of body fat (body mass index - BMI, waist circumference - WC and waist-hip ratio - WHR), as well as its relationship with diabetes, among elderly individuals living in urban areas in seven places in Brazil, according to gender. This is a cross-sectional study carried out with a probabilistic sample comprising 2,566 individuals with 65 years of age or more who participated in the FIBRA Study (Frailty in Elderly Brazilians). We used several self-reported sociodemographic variables (gender, age, race, schooling and family income), anthropometric measures of general (BMI) and abdominal obesity (WC and WHR) and self-reported diabetes. Adjusting for schooling and income, white race was associated with higher WC values (p = 0.001) and WHR (p > 0.001) for male gender, regardless of diabetes status. However, when we considered only diabetic individuals, black race became associated with general (BMI) (p = 0.007) and central obesity (CC) (p > 0.001), only among women.

  19. TWEAK: A New Player in Obesity and Diabetes

    PubMed Central

    Vendrell, Joan; Chacón, Matilde R.

    2013-01-01

    Obesity and type 2 diabetes (T2D) are associated with chronic low-grade inflammation. Mounting evidence suggests the involvement of an inflammatory switch in adipose tissue, both in mature adipocytes and immune-competent cells from the stromal vascular compartment, in the progression of obesity and insulin resistance. Several inflammatory cytokines secreted by obese adipose tissue, including TNFα and IL-6 have been described as hallmark molecules involved in this process, impairing insulin signaling in insulin-responsive organs. An increasing number of new molecules affecting the local and systemic inflammatory imbalance in obesity and T2D have been identified. In this complex condition, some molecules may exhibit opposing actions, depending on the cell type and on systemic or local influences. Tumor necrosis factor weak inducer of apoptosis (TWEAK), a cytokine of the tumor necrosis (TNF) superfamily, is gaining attention as an important player in chronic inflammatory diseases. TWEAK can exist as a full-length membrane-associated (mTWEAK) form and as a soluble (sTWEAK) form and, by acting through its cognate receptor Fn14, can control many cellular activities including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. Notably, sTWEAK has been proposed as a biomarker of cardiovascular diseases. Here, we will review the recent findings relating to TWEAK and its receptor within the context of obesity and the associated disorder T2D. PMID:24416031

  20. Vitamin D: Link between Osteoporosis, Obesity, and Diabetes?

    PubMed Central

    Cândido, Flávia Galvão; Bressan, Josefina

    2014-01-01

    Vitamin D (1,25(OH)2D3) is a steroid hormone that has a range of physiological functions in skeletal and nonskeletal tissues, and can contribute to prevent and/or treat osteoporosis, obesity, and Type 2 diabetes mellitus (T2DM). In bone metabolism, vitamin D increases the plasma levels of calcium and phosphorus, regulates osteoblast and osteoclast the activity, and combats PTH hypersecretion, promoting bone formation and preventing/treating osteoporosis. This evidence is supported by most clinical studies, especially those that have included calcium and assessed the effects of vitamin D doses (≥800 IU/day) on bone mineral density. However, annual megadoses should be avoided as they impair bone health. Recent findings suggest that low serum vitamin D is the consequence (not the cause) of obesity and the results from randomized double-blind clinical trials are still scarce and inconclusive to establish the relationship between vitamin D, obesity, and T2DM. Nevertheless, there is evidence that vitamin D inhibits fat accumulation, increases insulin synthesis and preserves pancreatic islet cells, decreases insulin resistance and reduces hunger, favoring obesity and T2DM control. To date, there is not enough scientific evidence to support the use of vitamin D as a pathway to prevent and/or treat obesity and T2DM. PMID:24747593

  1. Vitamin D: link between osteoporosis, obesity, and diabetes?

    PubMed

    Cândido, Flávia Galvão; Bressan, Josefina

    2014-04-17

    Vitamin D (1,25(OH)2D3) is a steroid hormone that has a range of physiological functions in skeletal and nonskeletal tissues, and can contribute to prevent and/or treat osteoporosis, obesity, and Type 2 diabetes mellitus (T2DM). In bone metabolism, vitamin D increases the plasma levels of calcium and phosphorus, regulates osteoblast and osteoclast the activity, and combats PTH hypersecretion, promoting bone formation and preventing/treating osteoporosis. This evidence is supported by most clinical studies, especially those that have included calcium and assessed the effects of vitamin D doses (≥800 IU/day) on bone mineral density. However, annual megadoses should be avoided as they impair bone health. Recent findings suggest that low serum vitamin D is the consequence (not the cause) of obesity and the results from randomized double-blind clinical trials are still scarce and inconclusive to establish the relationship between vitamin D, obesity, and T2DM. Nevertheless, there is evidence that vitamin D inhibits fat accumulation, increases insulin synthesis and preserves pancreatic islet cells, decreases insulin resistance and reduces hunger, favoring obesity and T2DM control. To date, there is not enough scientific evidence to support the use of vitamin D as a pathway to prevent and/or treat obesity and T2DM.

  2. AGE, RAGE, and ROS in diabetic nephropathy.

    PubMed

    Tan, Adeline L Y; Forbes, Josephine M; Cooper, Mark E

    2007-03-01

    Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Two key mechanisms implicated in the development of diabetic nephropathy include advanced glycation and oxidative stress. Advanced glycation is the irreversible attachment of reducing sugars onto amino groups of proteins to form advanced glycation end products (AGEs). AGE modification of proteins may lead to alterations in normal function by inducing cross-linking of extracellular matrices. Intracellular formation of AGEs also can cause generalized cellular dysfunction. Furthermore, AGEs can mediate their effects via specific receptors, such as the receptor for AGE (RAGE), activating diverse signal transduction cascades and downstream pathways, including generation of reactive oxygen species (ROS). Oxidative stress occurs as a result of the imbalance between ROS production and antioxidant defenses. Sources of ROS include the mitochondria, auto-oxidation of glucose, and enzymatic pathways including nicotinamide adenine dinucleotide phosphate reduced (NAD[P]H) oxidase. Beyond the current treatments to treat diabetic complications such as the optimization of blood pressure and glycemic control, it is predicted that new therapies designed to target AGEs, including AGE formation inhibitors and cross-link breakers, as well as targeting ROS using novel highly specific antioxidants, will become part of the treatment regimen for diabetic renal disease.

  3. Prevalence and Associated Factors of Diabetes and Impaired Fasting Glucose in Chinese Hypertensive Adults Aged 45 to 75 Years

    PubMed Central

    Zhang, Yan; Ma, Wei; Fan, Fangfang; Wang, Binyan; Xing, Houxun; Tang, Genfu; Wang, Xiaobin; Xu, Xin; Xu, Xiping; Huo, Yong

    2012-01-01

    Objective This study examined the prevalence of impaired fasting glucose (IFG) and diabetes and their associated factors in 17,184 Chinese hypertensive adults aged 45–75 years. Methods A cross-sectional investigation was carried out in a rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma glucose (FPG) ≥7.0mmol/l] and IFG (6.1–6.9mmol/l) were defined based on FPG concentration. Previously diagnosed diabetes was determined on the basis of self-report. Total diabetes included both previously diagnosed diabetes and previously undiagnosed diabetes. Results The prevalence of previously diagnosed diabetes, undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About 74.2% of the participants with diabetes had not previously been diagnosed. In the multivariable logistic-regression model, older age, men, antihypertensive treatment, obesity (BMI ≥25kg/m2), abdominal obesity (waist circumference ≥90cm for men and ≥80cm for women), non-current smoking, a family history of diabetes, higher heart rate, lower physical activity levels, and inland residence (versus coastal) were significantly associated with both total diabetes and previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate reductase (MTHFR) 677 TT genotype was an independent associated factor for total diabetes, and current alcohol drinking was an independent associated factor for previously undiagnosed diabetes. At the same time, older age, men, abdominal obesity, non-current smoking, current alcohol drinking, a family history of diabetes, higher heart rate, and inland residence (versus coastal) were important independent associated factors for IFG. Conclusion In conclusion, we found a high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about three out of every four diabetic adults were undiagnosed. Our results suggest that population-level measures aimed at the prevention, identification (even if only based on the FPG

  4. Obesity and its Association with Food Consumption, Diabetes Mellitus, and Acute Myocardial Infarction in the Elderly

    PubMed Central

    da Silveira, Erika Aparecida; Vieira, Liana Lima; Jardim, Thiago Veiga; de Souza, Jacqueline Danesio

    2016-01-01

    Background Obesity affects a large part of elderly individuals worldwide and is considered a risk predictor for the development of chronic diseases such as cardiac diseases, the leading causes of death in the elderly population. Objective To investigate the prevalence of obesity and associated factors, with emphasis on the occurrence of other diseases and on food consumption in elderly individuals treated at the Brazilian Unified Health System (Sistema Único de Saúde, SUS). Methods Cross-sectional sampling study performed in the city of Goiânia (Brazil) including elderly individuals (≥ 60 years) receiving primary care. During home visits, we performed anthropometric measurements and applied a structured, standardized, and pre-tested questionnaire assessing socioeconomic, demographic and lifestyle conditions, occurrence of diseases, and food consumption. We performed multiple Poisson regression analysis using a hierarchical model and adopting a significance level of 5%. Results We evaluated 418 elderly patients with a mean age of 70.7 ± 7 years. Their body mass indices had a mean value of 27.0 kg/m2 and were higher in women than in men (27.4 kg/m2 versus 26.1 kg/m2, respectively, p = 0.017). Obesity had a prevalence of 49.0%, a risk 1.87 times higher between the ages of 60-69 years and 70-79 years, and a rate 1.4 times higher among individuals with more than four morbidities. On multivariate analysis, the factors associated with obesity were age 60-69 and 70-79 years, inadequate consumption of whole-wheat grains and adequate consumption of fruit, musculoskeletal diseases, diabetes mellitus, and acute myocardial infarction. Conclusions Obesity had a high prevalence in the evaluated elderly population and was associated with food consumption, musculoskeletal disease, diabetes mellitus, and acute myocardial infarction.

  5. 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

  6. 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

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

    PubMed

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

    2013-01-01

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

  8. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-09-01

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

  11. 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.

  12. 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

  13. Resistin/ADSF/FIZZ3 in obesity and diabetes.

    PubMed

    Sul, Hei Sook

    2004-08-01

    The role of adipocyte-secreted resistin/adipocyte-specific secretory factor (ADSF)/FIZZ3 in obesity and diabetes has been controversial at best. Recently generated resn knockout mice showed normal glucose and insulin sensitivity with lower fasting glucose levels. Upon feeding with a high-fat diet, the knockout mice exhibited increased glucose tolerance with decreased hepatic glucose output, possibly due to phosphorylation and activation of AMP-activated protein kinase and suppression of gluconeogenic genes. In comparison, transgenic mice overexpressing a dominant negative form of resistin/ADSF/FIZZ3 showed increased adiposity with elevated leptin and adiponectin levels, accompanying enhanced glucose tolerance and insulin sensitivity both on chow and high-fat diets. Although its underlying mechanisms need further elucidation, the in vivo studies demonstrate a role of resistin/ADSF/FIZZ3 in obesity and insulin resistance.

  14. Fasting leptin and glucose in normal weight, over weight and obese men and women diabetes patients with and without clinical depression.

    PubMed

    Haleem, Darakhshan Jabeen; Sheikh, Shehnaz; Fawad, Asher; Haleem, Muhammad A

    2017-02-15

    A large number of diabetes patients suffer from major depression and are at high risk of mortality. In view of a role of leptin in diabetes, depression and energy homeostasis, the present study concerns circulating levels of leptin in different BMI groups of un-depressed and depressed diabetes patients. Six hundred thirty male and female patients with a primary diagnosis of diabetes were grouped according to BMI and with or without clinical symptoms of depression. Age matched healthy, normal weight male and female volunteers without clinical symptoms of depression or diabetes were taken as controls. Blood samples were obtained after an overnight fast of 12 h. Serum was stored for the determination of leptin and glucose. We found that there were more female than male diabetes patients with comorbid depression. Fasting leptin was higher in normal weight non-diabetes women than men; but comparable in normal weight men and women diabetes patients. Fasting glucose levels were higher in diabetes than non diabetes groups; values were comparable in men and women. Depression was associated with a decrease and increase in leptin respectively in normal-overweight and obese men and women diabetes patients. Glucose levels were also higher in obese depressed than un-depressed diabetes patients. The results suggested that the female gender is at greater risk to comorbid diabetes with depression. Adipo-insular axis plays an important role in diabetes, associated depression and in the greater risk of the female gender to comorbid diabetes with depression.

  15. 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,…

  16. Obesity and periodontal disease in diabetic pregnant women.

    PubMed

    Chapper, Ana; Munch, Artur; Schermann, Camila; Piacentini, Carolina Carraro; Fasolo, Maria Thereza Martins

    2005-01-01

    This cross-sectional study investigated the impact of pregestational overweight and obesity on periodontal status of patients with gestational diabetes mellitus (GDM). Sixty pregnant women with gestational diabetes mellitus (GDM) were recruited for the study. According to the pregestational body mass index (BMI), patients were classified into 3 groups: normal, overweight or obese. The periodontal assessment parameters were the presence of gingival bleeding (GB) and bleeding on probing (BOP) per tooth. Clinical attachment loss (CAL) was assessed per tooth and classified according to following values: 1) absence of attachment loss; 2) between 1 and 2 mm, 3) between 3 and 5 mm; and 4) CAL > or = 6 mm. The means of individual percentage of teeth with GB and BOP and the means of the individual classified values of CAL were compared through ANOVA. Differences between the groups were established through post hoc Bonferroni test for multiple comparisons (p < 0.05). The analysis revealed significant differences between the normal group and the obese group considering GB (52.76% +/- 27.99% and 78.85% +/- 27.44%, respectively) and CAL (2.21 +/- 0.41 and 2.61 +/- 0.54, respectively). Although an increase was found in BOP as the BMI increased (ranging from 55.65% to 75.31%), no statistically significant differences were found among the groups. Patients with GDM and pregestational obesity had significantly more gingivitis and periodontal attachment loss that those with normal pregestational BMI. Periodontal treatment should be considered in the establishment of future recommendations for metabolic control for this special group of patients.

  17. Racializing narratives: obesity, diabetes and the "Aboriginal" thrifty genotype.

    PubMed

    Fee, Margery

    2006-06-01

    This post-colonial reading of narratives of obesity, diabetes, and the hypothesized "thrifty genotype" ascribed to Aboriginal peoples shows how scientific and popular texts support the belief in biological "race." Although the scientific consensus is that "race" is not a empirical category, many scientists use it without comment as a "crude proxy" for presumed genetic differences. The division between science and the social sciences/humanities protects such confusing practices from full scientific and social critique, something interdisciplinary research teams, science studies and improved peer review could provide.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-04-01

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

  20. Obesity diabetes and the role of bile acids in metabolism

    PubMed Central

    Owens, Daphne

    2016-01-01

    Abstract Bile acids have many activities over and above their primary function in aiding absorption of fat and fat soluble vitamins. Bile acids are synthesized from cholesterol, and thus are involved in cholesterol homeostasis. Bile acids stimulate glucagon-like peptide 1 (GLP1) production in the distal small bowel and colon, stimulating insulin secretion, and therefore, are involved in carbohydrate and fat metabolism. Bile acids through their insulin sensitising effect play a part in insulin resistance and type 2 diabetes. Bile acid metabolism is altered in obesity and diabetes. Both dietary restriction and weight loss due to bariatric surgery, alter the lipid carbohydrate and bile acid metabolism. Recent research suggests that the forkhead transcription factor FOXO is a central regulator of bile, lipid, and carbohydrate metabolism, but conflicting studies mean that our understanding of the complexity is not yet complete. PMID:28191525

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

    PubMed

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

    2008-10-01

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

  2. Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.

    PubMed

    Agil, Ahmad; El-Hammadi, Mazen; Jiménez-Aranda, Aroa; Tassi, Mohamed; Abdo, Walied; Fernández-Vázquez, Gumersindo; Reiter, Russel J

    2015-08-01

    Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates liver steatosis and vacuolation, and also mitigates diabetic-induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity.

  3. Obesity and underweight among Brazilian elderly: the Bambuí Health and Aging Study.

    PubMed

    Barreto, Sandhi M; Passos, Valéria M A; Lima-Costa, Maria Fernanda F

    2003-01-01

    The coexistence of obesity (body mass index, BMI > or = 30kg/m ) and underweight (BMI <= 20kg/m ) and related factors were investigated among all residents aged 60+ years in Bambu , Minas Gerais State, using multinomial logistic regression. 1,451 (85.5%) of the town's elderly participated. Mean BMI was 25.0 (SD = 4.9kg/m ) and was higher for women and decreased with age. Prevalence of obesity was 12.5% and was positively associated with female gender, family income, hypertension, and diabetes and inversely related to physical activity. Underweight affected 14.8% of participants, increased with age, and was higher among men and low-income families. It was negatively associated with hypertension and diabetes and directly associated with Trypanosoma cruzi infection and > or = 2 hospitalizations in the previous 12 months. Both obesity and underweight were associated with increased morbidity. The association of underweight with T. cruzi infection, increased hospitalization, and low family income may reflect illness-related weight loss and social deprivation of elderly in this community. Aging in poverty may lead to an increase in nutritional deficiencies and health-related problems among the elderly.

  4. New insights on diabetes mellitus and obesity in Africa-part 1: prevalence, pathogenesis and comorbidities.

    PubMed

    Kengne, Andre Pascal; Echouffo-Tcheugui, Justin-Basile; Sobngwi, Eugene; Mbanya, Jean-Claude

    2013-07-01

    Evidence continues to accumulate on the rising burden of diabetes mellitus at a higher pace in Africa. In a series of two papers, we sought to summarise recent evidence on diabetes and obesity in Africa based on a systematic review of studies published between January 2002 and October 2012. This first paper on the prevalence, pathogenesis and comorbidities shows that the increase in diabetes prevalence has paralleled that of obesity in Africa. Recent surveys on diabetes and obesity have been largely suboptimal. Hence, the need for more representative and robust continent-wide prevalence figures, which may be somehow achieved through pooling of existing data. Prospective studies linking environmental risk factors to disease occurrence and outcomes remain scarce, and genetic factors for diabetes or obesity have not been extensively assessed. The health consequences of diabetes are manifold, and include a complex interaction with other conditions like HIV infection and sickle cell disease/trait.

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

    PubMed

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

    1988-12-01

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

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

    PubMed Central

    Speakman, John R.; Heidari-Bakavoli, Sahar

    2016-01-01

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

  7. Early Antenatal Prediction of Gestational Diabetes in Obese Women: Development of Prediction Tools for Targeted Intervention

    PubMed Central

    White, Sara L.; Lawlor, Debbie A.; Briley, Annette L.; Nelson, Scott M.; Oteng-Ntim, Eugene; Sattar, Naveed; Seed, Paul T.; Welsh, Paul; Whitworth, Melissa; Poston, Lucilla; Pasupathy, Dharmintra

    2016-01-01

    All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0–18+6 weeks’ gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68–0.74). This increased to 0.77 (95%CI 0.73–0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74–0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described

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

    PubMed

    Ekart, Robert; Hojs, Radovan

    2016-07-01

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

  9. Effect of Diabetes and Obesity on Disparities in Prostate Cancer Outcomes

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0503 TITLE: “Effect of Diabetes and Obesity on Disparities in Prostate Cancer Outcomes PRINCIPAL INVESTIGATOR: Bettina F...RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE Annual 3. DATES COVERED 20154. TITLE AND SUBTITLE Effect of Diabetes ... diabetes (at prostate cancer diagnosis and during follow- up) and prostate cancer recurrence and mortality; as well as the combined effect of obesity

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

    PubMed

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

    2013-10-01

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

  11. The endocannabinoid system in obesity and type 2 diabetes.

    PubMed

    Di Marzo, V

    2008-08-01

    Endocannabinoids (ECs) are defined as endogenous agonists of cannabinoid receptors type 1 and 2 (CB1 and CB2). ECs, EC anabolic and catabolic enzymes and cannabinoid receptors constitute the EC signalling system. This system participates in the control of lipid and glucose metabolism at several levels, with the possible endpoint of the accumulation of energy as fat. Following unbalanced energy intake, however, the EC system becomes dysregulated, and in most cases overactive, in several organs participating in energy homeostasis, particularly, in intra-abdominal adipose tissue. This dysregulation might contribute to excessive visceral fat accumulation and reduced adiponectin release from this tissue, and to the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes. This phenomenon might form the basis of the mechanism of action of CB1 antagonists/inverse agonists, recently developed by several pharmaceutical companies as adjuvants to lifestyle modification for weight reduction, glycaemic control and dyslipidaemia in obese and type 2 diabetes patients. It also helps to explain why some of the beneficial actions of these new therapeutics appear to be partly independent from weight loss.

  12. Canagliflozin: Effects in overweight and obese subjects without diabetes mellitus

    PubMed Central

    Bays, Harold E; Weinstein, Richard; Law, Gordon; Canovatchel, William

    2014-01-01

    Objective To evaluate the effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on body weight in overweight and obese subjects (body mass index [BMI] ≥27 and <50 kg/m2). Methods This 12-week, Phase 2b, randomized, double-blind study enrolled 376 subjects without diabetes mellitus who received canagliflozin 50, 100, or 300 mg or placebo once daily. The primary endpoint was the percent change in body weight from baseline through Week 12. Results Canagliflozin increased urinary glucose excretion in a dose-dependent manner and produced statistically significant reductions in body weight compared with placebo (least squares mean percent changes from baseline of −2.2%, −2.9%, −2.7%, and −1.3% with canagliflozin 50, 100, and 300 mg and placebo; P < 0.05 for all comparisons). Overall adverse event (AE) rates were similar across groups. Canagliflozin was associated with higher rates of genital mycotic infections in women, which were generally mild and led to few study discontinuations. Osmotic diuresis-related AE rates were low and similar across groups. Conclusions In overweight and obese subjects without diabetes mellitus, canagliflozin significantly reduced body weight compared with placebo and was generally well tolerated. PMID:24227660

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

    PubMed

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

    2012-03-01

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

  14. Obstructive Sleep Apnea Among Obese Patients With Type 2 Diabetes

    PubMed Central

    Foster, Gary D.; Sanders, Mark H.; Millman, Richard; Zammit, Gary; Borradaile, Kelley E.; Newman, Anne B.; Wadden, Thomas A.; Kelley, David; Wing, Rena R.; Pi Sunyer, F. Xavier; Darcey, Valerie; Kuna, Samuel T.

    2009-01-01

    OBJECTIVE To assess the risk factors for the presence and severity of obstructive sleep apnea (OSA) among obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Unattended polysomnography was performed in 306 participants. RESULTS Over 86% of participants had OSA with an apnea-hypopnea index (AHI) ≥5 events/h. The mean AHI was 20.5 ± 16.8 events/h. A total of 30.5% of the participants had moderate OSA (15 ≤ AHI <30), and 22.6% had severe OSA (AHI ≥30). Waist circumference (odds ratio 1.1; 95% CI 1.0–1.1; P = 0.03) was significantly related to the presence of OSA. Severe OSA was most likely in individuals with a higher BMI (odds ratio 1.1; 95% CI 1.0–1.2; P = 0.03). CONCLUSIONS Physicians should be particularly cognizant of the likelihood of OSA in obese patients with type 2 diabetes, especially among individuals with higher waist circumference and BMI. PMID:19279303

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

    PubMed Central

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

    2012-01-01

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

  16. Study Design of the Maycoba Project: Obesity and Diabetes in Mexican Pimas

    PubMed Central

    Urquidez-Romero, Rene; Esparza-Romero, Julian; Chaudhari, Lisa S.; Begay, R. Cruz; Giraldo, Mario; Ravussin, Eric; Knowler, William C.; Hanson, Robert L.; Bennett, Peter H.; Schulz, Leslie O.; Valencia, Mauro E.

    2016-01-01

    Objective To focus on the rationale and methods of the Maycoba Project. Methods Study population included Mexican Pima Indians (MPI) and Blancos aged ≥20-years, living in the village of Maycoba and surrounding area. Surveys in 1995 and 2010 included a medical history, biochemical and anthropometric measurements. Additionally, socioeconomic, physical activity, and dietary interviews were conducted. The 2010 study incorporated investigations on type 2 diabetes (T2D) and obesity-associated genetic alleles and human-environment changes. Results The study results are limited to demographic data and description of the eligible and examined sample. Conclusions This study may yield important information on T2D and obesity etiology in a traditional population exposed to environmental changes. PMID:24636033

  17. 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.

  18. Diabetes and Altered Glucose Metabolism with Aging

    PubMed Central

    Kalyani, Rita Rastogi; Egan, Josephine M.

    2013-01-01

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

  19. 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.

  20. 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.

  1. [Influence of smoking and abdominal obesity on lung age].

    PubMed

    Sakamoto, Kyoko; Sonobe, Hiroshi; Hiroi, Ayako; Tanaka, Hiromi; Hino, Yumiko; Takahuta, Keisuke; Ikeda, Taeko; Habara, Toshiyuki

    2011-09-01

    Smoking is the riskiest factor for impairment of pulmonary function. Recent researches have indicated that abdominal obesity is also associated with the impairment. 'Lung age' is a novel index to evaluate respiratory function, and it is calculated from the data of the height, sex, and forced expiratory volume in 1-second. Using 'lung age' as an index, we studied on the relationship of 'lung age' to smoking, waist circumference, BMI, or metabolic syndrome. The study population included 1,681 persons who visited our Medical Checkup Office, and the population consisted of smoker group (n = 279) and non-smoker group (n = 1,402). In both men and women, 'lung age' was significantly higher in the smoker group than in non-smoker group (p < 0.05). In addition, the smoker group and non-smoker group were classified by waist circumference, BMI, and the presence of metabolic syndrome, respectively. As a result, 'lung age' of smoker with abdominal obesity group, smoker with obesity group, and smoker with metabolic syndrome group were significantly high. Furthermore, in multivariate linear regression analysis, we examined relation between 'lung age' and the following factors including gender, smoking, waist circumference, BMI and metabolic syndrome. There was closely related to 'lung age' in order of gender, smoking, metabolic syndrome, and waist circumference. Both smoking and abdominal obesity should be significant risk factors in increasing 'lung age'.

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

    PubMed Central

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

    2000-01-01

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

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

    PubMed

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

    1995-05-23

    Mice that carry the lethal yellow (Ay) or viable yellow (Avy) 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 "obese yellow" 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.

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

    PubMed

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

    2014-01-01

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

  5. 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

  6. 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

  7. 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.

  8. Role of PUFAs, the precursors of endocannabinoids, in human obesity and type 2 diabetes.

    PubMed

    Dain, Alejandro; Repossi, Gaston; Das, Undurti N; Eynard, Aldo Renato

    2010-06-01

    Polyunsaturated fatty acids (PUFAs) serve as precursors of the endocannabinoids (ECs) that are bioactive lipids molecules. Recent studies revealed that ECs participate in several physiological and pathological processes including obesity and type 2 diabetes mellitus. Here we review the experimental and clinical aspects of the role of endocannabinoids in obesity and type 2 diabetes mellitus and the modification of the endocannabinoids by exogenously administered PUFAs. Based on these evidences, we propose that the endocannabinoid system (ECS) can be modulated by exogenous manipulation of PUFAs that could help in the prevention and management of human diseases such as obesity, metabolic syndrome and type 2 diabetes mellitus.

  9. 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.

  10. 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

    Han, Liyuan; Tang, Linlin; Wang, Changyi; Chen, Zhongwei; Zhang, Tao; Chen, Sihan; Liu, Shengyuan; Peng, Xiaolin; Mai, Yifeng; Duan, Shiwei

    2014-09-01

    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.

  11. 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

  12. 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.

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

    PubMed

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

    2016-09-05

    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.

  14. 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

    2016-08-09

    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.

  15. Muscle Sympathetic Nerve Activity Is Associated with Liver Insulin Sensitivity in Obese Non-Diabetic Men.

    PubMed

    Chen, Daniel L T; Brown, Rachael; Liess, Carsten; Poljak, Anne; Xu, Aimin; Zhang, Jialiang; Trenell, Michael; Jenkins, Arthur; Chisholm, Donald; Samocha-Bonet, Dorit; Macefield, Vaughan G; Greenfield, Jerry R

    2017-01-01

    Introduction: Muscle sympathetic nerve activity (MSNA) may play a role in insulin resistance in obesity. However, the direction and nature of the relationship between MSNA and insulin resistance in obesity remain unclear. We hypothesized that resting MSNA would correlate inversely with both muscle and liver insulin sensitivity and that it would be higher in insulin-resistant vs. insulin-sensitive subjects. Materials and methods: Forty-five non-diabetic obese subjects were studied. As no significant relationships were found in women, the data presented in on 22 men aged 48 ± 12 years. Two-step (15 and 80 mU/m(2)/min) hyperinsulinaemic-euglycaemic clamps were performed using deuterated glucose to determine liver and muscle insulin sensitivity. Clinical and metabolic parameters were assessed. MSNA was measured via a microelectrode inserted percutaneously into the common peroneal nerve. Results: MSNA burst frequency correlated inversely with liver insulin sensitivity (r = -0.53, P = 0.02) and positively with the hepatokines C-reactive protein (CRP) and fibroblast growth factor (FGF)-19 (r = 0.57, P = 0.006, and r = -0.47, P = 0.03, respectively). MSNA burst frequency was lower in Liversen compared to Liverres (27 ± 5 vs. 38 ± 2 bursts per minute; P = 0.03). Muscle insulin sensitivity was unrelated to MSNA. Discussion: Sympathetic neural activation is related to liver insulin sensitivity and circulating hepatokines CRP and FGF-19 in non-diabetic obese men. These results suggest a potential hepato-endocrine-autonomic axis. Future studies are needed to clarify the influence of MSNA on liver insulin sensitivity in men.

  16. Muscle Sympathetic Nerve Activity Is Associated with Liver Insulin Sensitivity in Obese Non-Diabetic Men

    PubMed Central

    Chen, Daniel L. T.; Brown, Rachael; Liess, Carsten; Poljak, Anne; Xu, Aimin; Zhang, Jialiang; Trenell, Michael; Jenkins, Arthur; Chisholm, Donald; Samocha-Bonet, Dorit; Macefield, Vaughan G.; Greenfield, Jerry R.

    2017-01-01

    Introduction: Muscle sympathetic nerve activity (MSNA) may play a role in insulin resistance in obesity. However, the direction and nature of the relationship between MSNA and insulin resistance in obesity remain unclear. We hypothesized that resting MSNA would correlate inversely with both muscle and liver insulin sensitivity and that it would be higher in insulin-resistant vs. insulin-sensitive subjects. Materials and methods: Forty-five non-diabetic obese subjects were studied. As no significant relationships were found in women, the data presented in on 22 men aged 48 ± 12 years. Two-step (15 and 80 mU/m2/min) hyperinsulinaemic-euglycaemic clamps were performed using deuterated glucose to determine liver and muscle insulin sensitivity. Clinical and metabolic parameters were assessed. MSNA was measured via a microelectrode inserted percutaneously into the common peroneal nerve. Results: MSNA burst frequency correlated inversely with liver insulin sensitivity (r = −0.53, P = 0.02) and positively with the hepatokines C-reactive protein (CRP) and fibroblast growth factor (FGF)-19 (r = 0.57, P = 0.006, and r = −0.47, P = 0.03, respectively). MSNA burst frequency was lower in Liversen compared to Liverres (27 ± 5 vs. 38 ± 2 bursts per minute; P = 0.03). Muscle insulin sensitivity was unrelated to MSNA. Discussion: Sympathetic neural activation is related to liver insulin sensitivity and circulating hepatokines CRP and FGF-19 in non-diabetic obese men. These results suggest a potential hepato-endocrine-autonomic axis. Future studies are needed to clarify the influence of MSNA on liver insulin sensitivity in men. PMID:28293196

  17. Foods, obesity, and diabetes-are all calories created equal?

    PubMed

    Mozaffarian, Dariush

    2017-01-01

    Diet has become one of the top risk factors for poor health. The incidence of cardiometabolic disease in the United Sates, in Mexico, and in most countries is driven fundamentally by changes in diet quality. Weight gain has been typically framed as a problem of excess caloric intake, but, as reviewed in this paper, subtle changes in the quality of diet are associated with long-term weight gain. In order to successfully address obesity and diabetes, researchers and policy makers have to better understand how weight gain in the long term is modulated and to change the focus of research and public policy from one based on counting calories to one based on diet quality and its determinants at various levels.

  18. The non-obese diabetic (NOD) mouse as a model of human type 1 diabetes.

    PubMed

    Kachapati, Kritika; Adams, David; Bednar, Kyle; Ridgway, William M

    2012-01-01

    The non-obese diabetic (NOD) mouse spontaneously develops type 1 diabetes (T1D) and has thus served as a model for understanding the genetic and immunological basis, and treatment, of T1D. Since its initial description in 1980, however, the field has matured and recognized that prevention of diabetes in NOD mice (i.e., preventing the disease from occurring by an intervention prior to frank diabetes) is relatively easy to achieve and does not correlate well with curing the disease (after the onset of frank hyperglycemia). Hundreds of papers have described the prevention of diabetes in NOD mice but only a handful have described its actual reversal. The paradoxical conclusion is that preventing the disease in NOD mice does not necessarily tell us what caused the disease nor how to reverse it. The NOD mouse model is therefore best used now, with respect to human disease, as a way to understand the genetic and immunologic causes of and as a model for trying to reverse disease once hyperglycemia occurs. We describe how genetic approaches to identifying causative gene variants can be adapted to identify novel therapeutic agents for reversing new-onset T1D.

  19. Liraglutide for Type 2 diabetes and obesity: a 2015 update.

    PubMed

    Iepsen, Eva Winning; Torekov, Signe Sørensen; Holst, Jens Juul

    2015-01-01

    Subcutaneous liraglutide (Victoza(®), Novo Nordisk) was approved for the treatment of Type 2 diabetes mellitus (T2DM) in Europe in 2009 and in the USA in 2010. In December 2014, liraglutide 3.0 mg was approved by the Food and Drug Administration (FDA) and in March 2015 by the European Medicines Agency (EMA) for the treatment of chronic weight management under the brand name Saxenda(®) Novo Nordisk. Liraglutide causes a glucose-dependent increase in insulin secretion, decreases glucagon secretion and promotes weight loss by inhibiting appetite. Liraglutide probably induces satiety through activation of different areas in the hind brain and possibly by preserving free leptin levels. Recently, liraglutide has been suggested to protect against prediabetes and seems to prevent bone loss by increasing bone formation following diet-induced weight loss in obesity. This article not only covers the major clinical trials evaluating the effects of liraglutide in obesity and T2DM but also provides novel insights into the pharmacological mechanisms of liraglutide.

  20. 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.

  1. TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats

    PubMed Central

    Zambad, Shitalkumar P; Munshi, Siralee; Dubey, Amita; Gupta, Ram; Busiello, Rosa Anna; Lanni, Antonia; Goglia, Fernando; Gupta, Ramesh C; Chauthaiwale, Vijay; Dutt, Chaitanya

    2011-01-01

    Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our previous study we demonstrated that TRC150094, when administered to rats receiving a high-fat diet, stimulated mitochondrial fatty acid oxidation (FAO) and reduced visceral adiposity, opening an interesting perspective for a possible clinical application. In the present study, oral administration of TRC150094 to obese Zucker spontaneously hypertensive fatty rats (obese ZSF1) improved glucose tolerance and glycemic profile as well as attenuated a rise in blood pressure. Obese ZSF1 rats treated with TRC150094 also showed reduced hepatic steatosis, reduced progression of nephropathy, and improved skeletal muscle function. At the cellular level, TRC150094 induced a significant increase in mitochondrial respiration as well as an increased FAO in liver and skeletal muscle, ultimately resulting in reduced hepatic as well as total body fat accumulation, as evaluated by magnetic resonance spectroscopy and magnetic resonance imaging, respectively. If reproduced in humans, these results could confirm that TRC150094 may represent an attractive therapeutic agent to counteract multiple residual cardiovascular risk components. PMID:21448317

  2. Gut hormones and endothelial dysfunction in patients with obesity and diabetes.

    PubMed

    Iantorno, M; Campia, U; Di Daniele, N; Nistico, S; Forleo, G B; Cardillo, C; Tesauro, M

    2014-01-01

    Overweight and obesity are the fifth leading risk for global deaths and its prevalence has doubled since 1980. At least 2.8 million adults, worldwide, die each year as a result of being overweight or obese. The deleterious effects of obesity are tightly related to diabetes, as they are often clinically present in combination to confer increased cardiovascular mortality. Thus, patients with diabetes and obesity are known to develop accelerated atherosclerosis characterized by a dysfunctional endothelium and decreased nitric oxide bioavailability. Recent clinical studies support, indeed, the use of incretin-based antidiabetic therapies for vascular protection. Thus, attention has been focusing on gut hormones and their role, not only in the regulation of appetite but also in vascular health. Intervention directed at modulating these molecules has the potential to decrease mortality of patients with diabetes and obesity. This review will cover part of the ongoing research to understand the role of gut hormones on endothelial function and vascular health.

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

    PubMed Central

    Devalaraja, Samir; Jain, Shalini; Yadav, Hariom

    2011-01-01

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

  4. 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

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

    PubMed

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

    2015-03-01

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

  6. Education and obesity at age 40 among American adults

    PubMed Central

    Cohen, Alison K.; Rehkopf, David H.; Deardorff, Julianna; Abrams, Barbara

    2012-01-01

    Although many have studied the association between educational attainment and obesity, studies to date have not fully examined prior common causes and possible interactions by race/ethnicity or gender. It is also not clear if the relationship between actual educational attainment and obesity is independent of the role of aspired educational attainment or expected educational attainment. The authors use generalized linear log link models to examine the association between educational attainment at age 25 and obesity (BMI≥30) at age 40 in the USA’s National Longitudinal Survey of Youth 1979 cohort, adjusting for demographics, confounders, and mediators. Race/ethnicity but not gender interacted with educational attainment. In a complete case analysis, after adjusting for socioeconomic covariates from childhood, adolescence, and adulthood, among whites only, college graduates were less likely than high school graduates to be obese (RR= 0.69, 95%CI: 0.57, 0.83). The risk ratio remained similar in two sensitivity analyses when the authors adjusted for educational aspirations and educational expectations and analyzed a multiply imputed dataset to address missingness. This more nuanced understanding of the role of education after controlling for a thorough set of confounders and mediators helps advance the study of social determinants of health and risk factors for obesity. PMID:23246398

  7. Losartan and Ozagrel reverse retinal arteriolar constriction in non-obese diabetic mice

    PubMed Central

    Lee, Seungjun; Harris, Norman R.

    2008-01-01

    Objective Reductions in retinal blood flow are observed early in diabetes. Venules may influence arteriolar constriction and flow; therefore, we hypothesized that diabetes would induce the constriction of arterioles that are in close proximity to venules, with the constriction mediated by thromboxane and angiotensin II. Methods Using non-obese diabetic (NOD) mice, retinal measurements were performed 3 weeks following the age at which glucose levels exceeded 200 mg/dl, with accompanying experiments on age-matched normoglycemic NOD mice. The measurements included retinal arteriolar diameters and red blood cell velocities, and were repeated following an injection of the thromboxane synthase inhibitor Ozagrel. Mice were subdivided into equal groups given drinking water with or without the angiotensin II receptor antagonist Losartan. Results Retinal arterioles were constricted in hyperglycemic mice, with a significant reduction in flow. However, not all arterioles were equally affected; the vasoconstriction was limited to arterioles that were in closer proximity to venules. The arteriolar vasoconstriction (mean arteriolar diameters = 51 ± 1 μm vs 61 ± 1 μm in controls; p<0.01) was eliminated by both Ozagrel (61 ± 2 μm) and Losartan (63 ± 2 μm). Conclusion Venule-dependent arteriolar vasoconstriction in NOD mice is mediated by thromboxane and/or angiotensin II. PMID:18574741

  8. Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men

    PubMed Central

    Djousse, Luc; Song, Yiqing; Akinkuolie, Akintunde O.; Matsumoto, Chisa; Manson, JoAnn E.; Gaziano, J. Michael; Sesso, Howard D.

    2017-01-01

    Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (AAA) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no AAA at baseline, 471 reported a newly diagnosed AAA during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) < 25 kg/m2, the multivariable hazard ratio (HR [95% CI]) of newly diagnosed AAA was 1.30 [1.06–1.59] for BMI 25–<30 kg/m2 and 1.69 [1.24–2.30] for BMI ≥ 30 kg/m2. The risk of diagnosed AAA was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known AAA risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed AAA (HR = 0.79 [0.57–1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed AAA, particularly over longer follow-up. PMID:28326193

  9. Testing mediator variables in a resistance training intervention for obese adults with type 2 diabetes.

    PubMed

    Lubans, David R; Plotnikoff, Ronald C; Jung, Mary; Eves, Neil; Sigal, Ron

    2012-01-01

    A poor understanding of behaviour change mechanisms has hindered the development of effective physical activity interventions. The aim of this study was to identify potential mediators of change in a home-based resistance training (RT) program for obese individuals with type 2 diabetes. Obese individuals with type 2 diabetes (N = 48) were randomly allocated to either an RT intervention (n = 27) or a control group (n = 21) for the 16-week study period. The study sample included 16 men and 32 women and the mean age of participants was 54.4 (±11.7) years. Participants in the RT group received a multi-gym and dumbbells and home supervision from a certified personal trainer. RT behaviour was measured using a modified Godin Leisure Time Questionnaire. Social-cognitive constructs were measured and tested in a mediating variable framework using a product-of-coefficients test. The intervention had a significant effect on RT behaviour (p < 0.001) and muscular strength (p < 0.001). The intervention had a significant effect on RT planning strategies (p < 0.01), which mediated the effect of the intervention on RT behaviour. The home-based RT program successfully targeted participants' RT planning strategies which contributed to their exercise adherence.

  10. 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

  11. 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...

  12. 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...

  13. Increased alloreactivity and adverse outcomes in obese kidney transplant recipients are limited to those with diabetes mellitus.

    PubMed

    Schachtner, Thomas; Stein, Maik; Reinke, Petra

    2017-02-01

    Previous studies on patient and allograft outcomes of obese kidney transplant recipients (KTRs) remain controversial. To what extent obesity-related comorbidities contribute to adverse outcomes, however, hasn't been addressed. We studied all KTRs from 2005 to 2012. 29 (4%), 317 (48%), 217 (33%), 76 (12%), and 21 KTRs (4%) were identified as underweight, normal-weight, overweight, obese, and morbid obese, respectively. 33 of 97 obese KTRs (34%) had pre-existent diabetes. Samples were collected before transplantation and at +1, +2, +3months posttransplantation. Donor-reactive T-cells were measured using an interferon-γ Elispot assay. Obese KTRs showed an increased incidence pre-existent diabetes (p<0.001), but no differences for hypertension and coronary artery disease (p>0.05). Among obese KTRs, those with pre-existent diabetes showed inferior patient and allograft survival, worse allograft function, delayed graft function, and prolonged hospitalization (p<0.05). Interestingly, no differences were observed between obese non-diabetic, normal-weight diabetic, and normal-weight non-diabetic KTRs (p>0.05). Obese diabetic KTRs showed higher frequencies of donor-reactive T-cells pretransplantation (p<0.05). Our results suggest that the increased risk of mortality, allograft loss, delayed graft function, and prolonged hospitalization in obese KTRs is limited to those with diabetes. A state of obesity-related inflammation plus hyperglycemia may trigger increased alloreactivity and should call for adequate immunosuppression.

  14. Effects of aging on basal fat oxidation in obese humans.

    PubMed

    Solomon, Thomas P J; Marchetti, Christine M; Krishnan, Raj K; Gonzalez, Frank; Kirwan, John P

    2008-08-01

    Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2)max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P = .16); however, waist circumference was not different between groups (104.3 +/- 10.3 vs 102.1 +/- 12.6 cm, P = .65). Basal fat oxidation was 22% lower (1.42 +/- 0.14 vs 1.17 +/- 0.22 mg/kg fat-free mass per minute, P = .03) in older subjects. The VO(2)max was also decreased in older individuals (44.6 +/- 7.1 vs 38.3 +/- 6.0 mL/kg fat-free mass per minute, P = .03); but insulin sensitivity, lipemia, and leptinemia were not different between groups (P > .05). Fat oxidation was most related to age (r = -0.61, P = .003) and VO(2)max (r = 0.52, P = .01). These data suggest that aging per se is responsible for reduced basal fat oxidation and maximal oxidative capacity in older obese individuals, independent of changes in insulin resistance, body mass, and abdominal fat. This indicates that age, in addition to obesity, is an independent risk factor for weight gain and for the metabolic complications of elevated body fat.

  15. Diabetes Is the Main Factor Accounting for Hypomagnesemia in Obese Subjects

    PubMed Central

    Lecube, Albert; Baena-Fustegueras, Juan Antonio; Fort, José Manuel; Pelegrí, Dolors; Hernández, Cristina; Simó, Rafael

    2012-01-01

    Objective Type 2 diabetes (T2DM) and obesity are associated with magnesium deficiency. We aimed to determine whether the presence of type 2 diabetes and the degree of metabolic control are related to low serum magnesium levels in obese individuals. Methods A) Case-control study: 200 obese subjects [50 with T2DM (cases) and 150 without diabetes (controls)] prospectively recruited. B) Interventional study: the effect of bariatric surgery on serum magnesium levels was examined in a subset of 120 obese subjects (40 with type 2 diabetes and 80 without diabetes). Results Type 2 diabetic patients showed lower serum magnesium levels [0.75±0.07 vs. 0.81±0.06 mmol/L; mean difference −0.06 (95% CI −0.09 to −0.04); p<0.001] than non-diabetic patients. Forty-eight percent of diabetic subjects, but only 15% of non-diabetic subjects showed a serum magnesium concentration lower than 0.75 mmol/L. Significant negative correlations between magnesium and fasting plasma glucose, HbA1c, HOMA-IR, and BMI were detected. Multiple linear regression analysis showed that fasting plasma glucose and HbA1c independently predicted serum magnesium. After bariatric surgery serum magnesium increased only in those patients in whom diabetes was resolved, but remain unchanged in those who not, without difference in loss weight between groups. Changes in serum magnesium negatively correlated with changes in fasting plasma glucose and HbA1c. Absolute changes in HbA1c independently predicted magnesium changes in the multiple linear regression analysis. Conclusions Our results provide evidence that the presence of diabetes and the degree of metabolic control are essential in accounting for the lower levels of magnesium that exist in obese subjects. PMID:22291997

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

    PubMed

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

    2015-04-01

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

  17. Very severely obese patients have a high prevalence of type 2 diabetes mellitus and cardiovascular disease.

    PubMed

    Vinciguerra, Federica; Baratta, Roberto; Farina, Maria Grazia; Tita, Patrizia; Padova, Giuseppa; Vigneri, Riccardo; Frittitta, Lucia

    2013-06-01

    The prevalence of very severe obesity has increased progressively and faster than other classes of obesity over the last years. It is unclear whether the prevalence of obesity-related complications and health risks increases progressively or reaches a plateau above a certain degree of obesity. The aim of our study was to investigate whether the severity of obesity was correlated with the prevalence of type 2 diabetes mellitus (T2DM), impaired fasting glucose, impaired glucose tolerance (IGT), metabolic syndrome (MS), and cardiovascular diseases (CVDs) in a large cohort of patients with different degrees of obesity. A cross-sectional study was conducted in 938 obese patients without a previous diagnosis of diabetes. Patients were assigned to different categories of obesity: mild-moderate obesity (BMI 30-39.9 kg/m(2)), morbid obesity (BMI 40-49.9 kg/m(2)), and super-obesity (SO, BMI ≥50 kg/m(2)). The prevalence of IGF, IGT, screen-detected T2DM, MS, and CVD was higher in SO patients than in the other groups. Interestingly, the association between SO and either MS or CVD was independent of glucose tolerance status, indicating that factors other than glucose metabolism also favor cardio-metabolic complications in obese patients. In patients without screen-detected T2DM (n = 807), insulin sensitivity and secretion OGTT-derived indexes indicated that SO patients had the worst glucose homeostasis relative to the other categories of obesity, which was indicated by the most reduced disposition index in these patients, a predictor of future T2DM. In conclusion, SO patients have an extremely high prevalence of glucose metabolism deterioration, and cardio-metabolic complications are more prevalent in these patients compared to less obese patients.

  18. Elevation of circulating LOX-1 ligand levels in Zucker obese and diabetic rats.

    PubMed

    Wakabayashi, Ichiro; Shimomura, Tomoko; Nakanishi, Mamoru; Uchida, Kagehiro

    2015-01-01

    LOX-1 ligands containing apolipoprotein B (LAB) reflect ligand activity of LOX-1, which is a key molecule for initiation of atherosclerosis. The Zucker rat is a well-known model used for research on obesity and diabetes. Blood levels of LAB were compared among Zucker fatty (ZF), Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. Log-transformed LAB was significantly higher in ZF and ZDF rats than in control ZL rats, while no significant difference was found in log-transformed LAB of ZF and ZDF rats. This study for the first time demonstrated that circulating LOX-1 ligands were elevated in obesity and diabetes model rats.

  19. Reduced dermis thickness and AGE accumulation in diabetic abdominal skin.

    PubMed

    Niu, Yiwen; Cao, Xiaozan; Song, Fei; Xie, Ting; Ji, Xiaoyun; Miao, Mingyuan; Dong, Jiaoyun; Tian, Ming; Lin, Yuan; Lu, Shuliang

    2012-09-01

    Dermatological problems in diabetes might play an important role in the spontaneous ulcers and impaired wound healing that are seen in diabetic patients. Investigation of the cause of diabetic skin disorders is critical for identifying effective treatment. The abdominal full-thickness skin tissues of 33 patients (14 nondiabetic and 19 diabetic) were analyzed. The cell viability and malondialdehyde (MDA) production of fibroblasts were measured after advanced glycosylation end product (AGE)-bovine serum albumin (BSA) exposure. Cutaneous histological observation showed reduced thickness of the diabetic abdominal dermis with morphological characteristics of obscured multilayer epithelium and shortened, thinned, and disorganized collagen fibrils with focal chronic inflammatory cell infiltration when compared with controls of the same age. Accumulation of AGEs in diabetic skin was prominent. Less hydroxyproline, higher myeloperoxidase activity, and increased MDA content were detected in diabetic skin. In vitro, the time- and dose-dependent inhibitory effects of AGE-BSA on fibroblast viability as well as the fact that AGE-BSA could promote MDA production of fibroblasts were shown. It is shown that the accumulation of AGEs in diabetic skin tissue induces an oxidative damage of fibroblasts and acts as an important contributor to the thinner diabetic abdominal dermis. The authors believe that diabetic cutaneous properties at baseline may increase the susceptibility to injury, and diabetic wounds possess atypical origin in the repair process.

  20. The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism.

    PubMed

    Saboor Aftab, S A; Kumar, S; Barber, T M

    2013-03-01

    Obesity, secondary (hypogonadotrophic) hypogonadism (SH), sleep disorders [such as obstructive sleep apnoea (OSA)] and type 2 diabetes mellitus (T2DM) in men have complex interlinks both with respect to mutual aetiopathogenesis as well as therapeutics. Correction of the attendant hypogonadism in obese men may serve to break this link and have beneficial effects beyond restoration of normal sexual function. Male obesity-associated secondary hypogonadism (MOSH) should be regarded as a distinct clinical entity and subtype of SH. A high index of suspicion for the presence of MOSH must be maintained by clinicians when assessing obese men. The pathogenesis of MOSH remains incompletely understood. Furthermore, the optimal management of MOSH and its associated sequelae will require long-term prospective studies that in turn will inform the development of future clinical guidelines for this important and prevalent condition.

  1. Some pharmacological effects of cinnamon and ginger herbs in obese diabetic rats

    PubMed Central

    Shalaby, Mostafa Abbas; Saifan, Hamed Yahya

    2014-01-01

    Aims: The present study was designed to assess some pharmacological effects of cinnamon (CAE) and ginger (GAE) aqueous extracts in obese diabetic rats, and to elucidate the potential mechanisms. Materials and Methods: Forty-two Sprague-Dawley rats were randomized into 6 equal groups. Group 1 was a negative control and the other groups were rendered obese by feeding rats on high-fat diet for 4 weeks. The obese rats were subcutaneously injected with alloxan for 5*days to induce diabetes. Group 2 was a positive control, and Groups 3, 4, 5 and 6 were orally given CAE in doses 200 and 400 mg/kg and GAE in the same doses, respectively for 6 weeks. Blood samples were collected for serum biochemical analyses. Kidneys were dissected out to assay activity of tissue antioxidant enzymes: Superoxide dismutase, glutathione peroxidase and catalase. Results: CAE and GAE significantly reduced body weight and body fat mass; normalized serum levels of liver enzymes; improved lipid profile; decreased blood glucose and leptin and increased insulin serum levels in obese diabetic rats. Both extracts also increased activity of kidney antioxidant enzymes. Conclusion: CAE and GAE exhibit anti-obesity, hepatoprotective, hypolipidemic, antidiabetic and anti-oxidant effects in obese diabetic rats. These results confirm the previous reports on both extracts. The potential mechanisms underlying these effects are fully discussed and clarified. Our results affirm the traditional use of cinnamon and ginger for treating patients suffering from obesity and diabetes. The obese diabetic rat model used in this study is a novel animal model used in pharmacology researches. PMID:26401364

  2. Insulin resistance in Mexican Americans--a precursor to obesity and diabetes?

    PubMed

    McCarty, M F

    1993-10-01

    Mexican Americans appear to have a strong genetic predisposition to insulin resistance, android obesity, and type II diabetes, apparently as a function of Native American genetic heritage. Theoretical considerations suggest that insulin resistance may be a primary factor that plays a causative role in the induction of both obesity and diabetes. Measures which promote optimal insulin sensitivity--chromium picolinate, brewer's yeast, soluble fiber supplements, metformin, very-low-fat diet, exercise training--may have value for preventing, treating, or retarding the onset of obesity and diabetes, and merit clinical evaluation in this regard. Correction of insulin resistance may also lessen cardiovascular risk, in part by reducing LDL cholesterol and improving risk factors associated with Syndrome X. These comments are likely to be valid for other Native American groups at high risk for diabetes.

  3. Adolescent gynecomastia is associated with a high incidence of obesity, dysglycemia, and family background of diabetes mellitus

    PubMed Central

    Kulshreshtha, Bindu; Arpita, Arora; Rajesh, Patnaik T.; Sameek, Bhattacharya; Dutta, Deep; Neera, Sharma; Mohd, Mohsin

    2017-01-01

    Background: Gynecomastia during adolescence is common though etiology is not clear. We studied the clinical and hormonal profile of adolescent patients with gynecomastia. Methodology: Patients who had onset of breast development between age 10 and 20 years were included in this study. Their clinical profile, biochemical, and hormonal parameters were studied. Results: Of 94 patients with gynecomastia, 4 had hypogonadotropic hypogonadism, 4 had hypergonadotropic hypogonadism, and 1 had fibroadenosis, but in majority (90.4%), no apparent cause for breast enlargement was evident. In the idiopathic group, majority were obese (63%). Fourteen (16%) patients had impaired fasting glucose or impaired glucose tolerance. Another twenty patients had subtle abnormalities (high 1 h glucose or glucose peak at 2 h). Twenty-nine percent of lean and 38% of obese patients had mild abnormalities in glucose profile. Sixty percent of patients had family background of diabetes. Obese patients had lower testosterone as compared to lean patients; however, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were similar in the two groups. Conclusion: Gynecomastia during adolescence is associated with obesity, dysglycemia, and family background of diabetes mellitus. PMID:28217517

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

    PubMed

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

    2012-02-01

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

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

    PubMed Central

    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/m2. 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

  6. 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

  7. A study of cardiovascular function in Tsumura Suzuki obese diabetes, a new model mouse of type 2 diabetes.

    PubMed

    Kawada, Tomie; Miyata, Shigeo; Shimada, Tsutomu; Sanzen, Yoshiki; Ito, Minami; Hemmi, Chieko; Iizuka, Seiichi; Suzuki, Wataru; Mihara, Kiyoshi; Aburada, Masaki; Nakazawa, Mikio

    2010-01-01

    Diabetes mellitus is a well known and important risk factor for cardiovascular diseases, including heart failure. A new model of Type 2 diabetes, Tsumura Suzuki Obese Diabetes (TSOD) mice, was introduced recently into the research field of diabetes. The cardiac functions of TSOD mice were studied in comparison with Tsumura Suzuki Non Obesity (TSNO, non-diabetic control) mice, for the first time. In vivo cardiovascular functions were measured by echocardiography and cardiac catheterization at 7, 12 and 18 months old. TSOD mice had no deterioration of cardiac function despite the long-term persistence of severe obesity, hyperglycemia, hyperinsulinemia and hyperlipidemia, including high density lipoprotein (HDL)-cholesterol. No histopathological abnormalities were observed in the heart of TSOD mice, while several histological abnormalities were observed in the pancreas and kidney of TSOD mice. To investigate vascular endothelium function at 7 months old, intravenous injection of acetylcholine (ACh; 1, 3, 10 microg/kg)- and N(G)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg)-induced mean blood pressure (BP) changes were used. ACh decreased whereas L-NAME increased BP, and no significant differences in BP changes were observed between TSOD and TSNO mice. Moreover, ACh-induced relaxation of the thoracic aortae isolated from TSOD and TSNO mice with intact endothelium were not significantly different. These findings suggest that vascular endothelial cells in TSOD mice are not impaired. It was clearly demonstrated that despite obvious diabetes, cardiac functions of TSOD mice were not impaired even at 18 months old.

  8. 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

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

    PubMed Central

    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 mice and the development of humanized NOD mice, providing novel insights into human T1D. PMID:26403950

  10. 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

  11. 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

    2016-04-15

    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.

  12. 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

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

    PubMed

    Asato, Megumi; Ikeda, Hiroko; Kamei, Junzo

    2012-11-01

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

  14. Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases?

    PubMed

    Tsai, Sue; Clemente-Casares, Xavier; Revelo, Xavier S; Winer, Shawn; Winer, Daniel A

    2015-06-01

    Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes and cardiovascular disease. Although these disorders affect a significant proportion of the global population, the underlying mechanisms of disease remain poorly understood. The discovery of elevated tumor necrosis factor-α in adipose tissue as an inducer of obesity-associated insulin resistance marked a new era of understanding that a subclinical inflammatory process underlies the insulin resistance and metabolic dysfunction that precedes type 2 diabetes. Advances in the field identified components of both the innate and adaptive immune response as key players in regulating such inflammatory processes. As antigen specificity is a hallmark of an adaptive immune response, its role in modulating the chronic inflammation that accompanies obesity and type 2 diabetes begs the question of whether insulin resistance and type 2 diabetes can have autoimmune components. In this Perspective, we summarize current data that pertain to the activation and perpetuation of adaptive immune responses during obesity and discuss key missing links and potential mechanisms for obesity-related insulin resistance and type 2 diabetes to be considered as potential autoimmune diseases.

  15. Intestinal Dysbiosis, Gut Hyperpermeability and Bacterial Translocation: Missing Links Between Depression, Obesity and Type 2 Diabetes.

    PubMed

    Slyepchenko, Anastasiya; Maes, Michael; Machado-Vieira, Rodrigo; Anderson, George; Solmi, Marco; Sanz, Yolanda; Berk, Michael; Köhler, Cristiano A; Carvalho, André F

    2016-01-01

    The comorbid prevalence of major depressive disorder (MDD) with obesity and type II diabetes mellitus reflects the existence of a subset of individuals with a complex common pathophysiology and overlapping risk factors. Such comorbid disease presentations imply a number of difficulties, including: decreased treatment responsivity and adherence; altered glycemic control and increased risk of wider medical complications. A number of factors link MDD to metabolic-associated disorders, including: higher rates of shared risk factors such as poor diet and physical inactivity and biological elements including increased inflammation; insulin resistance; oxidative and nitrosative stress; and mitochondrial dysfunction. All of these biological factors have been extensively investigated in the pathophysiology of obesity and type 2 diabetes mellitus as well as MDD. In this review, we aim to: (1) overview the epidemiological links between MDD, obesity and type 2 diabetes mellitus; (2) discuss the role of synergistic neurotoxic effects in MDD comorbid with obesity, and type 2 diabetes mellitus; (3) review evidence of intestinal dysbiosis, leaky gut and increased bacterial translocation, in the pathophysiology of MDD, obesity and type 2 diabetes mellitus; and (4) propose a model in which the gut-brain axis could play a pivotal role in the comorbidity of these disorders.

  16. Exercise increases hexokinase II mRNA, but not activity in obesity and type 2 diabetes.

    PubMed

    Cusi, K J; Pratipanawatr, T; Koval, J; Printz, R; Ardehali, H; Granner, D K; Defronzo, R A; Mandarino, L J

    2001-05-01

    Glucose phosphorylation, catalyzed by hexokinase, is the first committed step in glucose uptake in skeletal muscle. Hexokinase II (HKII) is the isoform that is present in muscle and is regulated by insulin and muscle contraction. Glucose phosphorylation and HKII expression are both reduced in obese and type 2 diabetic subjects. A single bout of exercise increases HKII mRNA and activity in muscle from healthy subjects. The present study was performed to determine if a moderate exercise increases HKII mRNA expression and activity in patients with type 2 diabetes. Muscle biopsies were performed before and 3 hours after a single bout of cycle ergometer exercise in obese and type 2 diabetic patients. HKII mRNA and activity and glycogen synthase activity were determined in the muscle biopsies. Exercise increased HKII mRNA in obese and diabetic subjects by 1.67 +/- 0.34 and 1.87 +/- 0.26-fold, respectively (P <.05 for both). Exercise did not significantly increase HKI mRNA. When HKII mRNA increases were compared with the 2.26 +/- 0.36-fold increase in HKII mRNA previously reported for healthy lean subjects, no statistically significant differences were found. In contrast to the increase in HKII activity observed after exercise by lean healthy controls, exercise did not increase HKII activity in obese nondiabetic or diabetic subjects. Exercise increased glycogen synthase activity (GS(0.1) and GS(FV)) significantly in both obese nondiabetic and type 2 diabetic patients. The present results indicate that there is a posttranscriptional defect in the response of HKII expression to exercise in obese and type 2 diabetic subjects. This defect may contribute to reduced HKII activity and glucose uptake in these patients.

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

    PubMed

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

    2008-05-23

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

  18. 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

  19. Beneficial effects of melatonin on obesity and lipid profile in young Zucker diabetic fatty rats.

    PubMed

    Agil, Ahmad; Navarro-Alarcón, Miguel; Ruiz, Rosario; Abuhamadah, Sawsan; El-Mir, Mohamad-Yehia; Vázquez, Gumersindo Fernández

    2011-03-01

    The study objective was to investigate the effects of melatonin on obesity and obesity-associated systolic hypertension and dyslipidemia in young male Zucker diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome. ZDF rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty animals were subdivided into three groups (n=10): naive (N), vehicle-treated (V), and melatonin-treated (M) (10mg/kg/day) for 6wk. Vehicle and melatonin were added to the drinking water. Melatonin reduced mean weight gain (51±2/100g BW) versus N-ZDF group (58±3, P<0.05) without food intake differences. M-ZDF rats showed an apparent reduction in systolic hypertension that proved not to be statistically significant, and a significant improvement in dyslipidemia, with a reduction in hypertriglyceridemia from 580±40 to 420.6±40.9mg/dL (P<0.01). Melatonin raised high-density-lipoprotein (HDL) cholesterol in ZDF (from 81.6±4.9 to 103.1±4.5mg/dL, P<0.01) and ZL rats (from 62.8±4.8 to 73.5±4.8mg/dL, P<0.05) and significantly reduced low-density-lipoprotein (LDL) cholesterol in ZDF rats from 5.20±0.4 to 4.14±0.3 mg/dL (P<0.05) but had no effect on total cholesterol levels. To our knowledge, this is the first evidence of a positive effect of melatonin on overweight and lipid pattern of obese Zucker diabetic rats, supporting the proposition that melatonin administration may ameliorate overweight and lipid metabolism in humans. Because these benefits occurred in youth, before advanced metabolic and vascular complications, melatonin might help to prevent cardiovascular disease associated with obesity and dyslipidemia.

  20. 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.

  1. Non-Obese Diabetic Mice Rapidly Develop Dramatic Sympathetic Neuritic Dystrophy

    PubMed Central

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

    2003-01-01

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

  2. 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

  3. Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

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

  5. 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…

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Salois, Matthew J

    2012-01-01

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

  8. Bariatric Surgery to Correct Morbid Obesity Also Ameliorates Atherosclerosis in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Wang, Yong; Zhang, Cuihua

    2009-01-01

    Morbid obesity, a physiological dysfunction in humans associated with environmental, genetic and endocrinological origins, has significantly increased in the past few decades in the USA. Many methods have emerged for treating morbid obesity, such as diets, exercise, behavior modification, liposuction, drugs, and surgery; among these, bariatric surgery reduces weight and appears to have other curative effects. Roux-en-Y gastric bypass is the principal form of bariatric surgery, followed by laparoscopic adjustable gastric banding, gastric sleeve operation, duodenojejunal bypass and biliopancreatic diversion. This weight-loss surgery may also affect comorbidities of morbid obesity, such as type 2 diabetes mellitus (T2D), atherosclerosis, hypertension and steatohepatitis. Weight-loss surgery, for example, is associated with a more than 80% diabetes (data indicates > 80%) remission rate in severely obese persons. Empirical evidence also suggests that the use of bariatric surgery reduces atherosclerosis, and may ameliorate other comorbities. This warrants closer examination. PMID:19915685

  9. Advanced Glycation End Products (AGE) and Diabetes: Cause, Effect, or Both?

    PubMed Central

    Vlassara, Helen; Uribarri, Jaime

    2014-01-01

    Despite new and effective drug therapies, insulin resistance (IR), type 2 diabetes mellitus (T2D) and its complications remain major medical challenges. It is accepted that IR, often associated with over-nutrition and obesity, results from chronically elevated oxidant stress (OS) and chronic inflammation. Less acknowledged is that a major cause for this inflammation is excessive consumption of advanced glycation end products (AGEs) with the standard western diet. AGEs, which were largely thought as oxidative derivatives resulting from diabetic hyperglycemia, are increasingly seen as a potential risk for islet β-cell injury, peripheral IR and diabetes. Here we discuss the relationships between exogenous AGEs, chronic inflammation, IR, and T2D. We propose that under chronic exogenous oxidant AGE pressure the depletion of innate defense mechanisms is an important factor, which raises susceptibility to inflammation, IR, T2D and its complications. Finally we review evidence on dietary AGE restriction as a non-pharmacologic intervention, which effectively lowers AGEs, restores innate defenses and improves IR, thus, offering new perspectives on diabetes etiology and therapy. PMID:24292971

  10. Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity.

    PubMed

    López-Lluch, Guillermo

    2017-03-01

    Mitochondria play an essential role in ageing and longevity. During ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological activities in the organism. Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis. Three major nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology. These nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy. Apart of the known factors involved in fusion, OPA1 and mitofusins, and fission, DRP1 and FIS1, emerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation. Mitochondria is also affected by sexual hormones that suffer drastic changes during ageing. The recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver. In this article, the role of mitochondrial homeostasis in ageing and age-dependent fat accumulation is revised. This review highlights the importance of mitochondria in the accumulation of fat during ageing and related diseases such as obesity, metabolic syndrome or type 2 diabetes mellitus.

  11. Saturated fatty acids activate ERK signaling to downregulate hepatic sortilin 1 in obese and diabetic mice.

    PubMed

    Bi, Lipeng; Chiang, John Y L; Ding, Wen-Xing; Dunn, Winston; Roberts, Benjamin; Li, Tiangang

    2013-10-01

    Hepatic VLDL overproduction is a characteristic feature of diabetes and an important contributor to diabetic dyslipidemia. Hepatic sortilin 1 (Sort1), a cellular trafficking receptor, is a novel regulator of plasma lipid metabolism and reduces plasma cholesterol and triglycerides by inhibiting hepatic apolipoprotein B production. Elevated circulating free fatty acids play key roles in hepatic VLDL overproduction and the development of dyslipidemia. This study investigated the regulation of hepatic Sort1 in obesity and diabetes and the potential implications in diabetic dyslipidemia. Results showed that hepatic Sort1 protein was markedly decreased in mouse models of type I and type II diabetes and in human individuals with obesity and liver steatosis, whereas increasing hepatic Sort1 expression reduced plasma cholesterol and triglycerides in mice. Mechanistic studies showed that the saturated fatty acid palmitate activated extracellular signal-regulated kinase (ERK) and inhibited Sort1 protein by mechanisms involving Sort1 protein ubiquitination and degradation. Consistently, hepatic ERK signaling was activated in diabetic mice, whereas blocking ERK signaling by an ERK inhibitor increased hepatic Sort1 protein in mice. These results suggest that increased saturated fatty acids downregulate liver Sort1 protein, which may contribute to the development of dyslipidemia in obesity and diabetes.

  12. 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

  13. METABOLIC ASTHMA: IS THERE A LINK BETWEEN OBESITY, DIABETES AND ASTHMA?

    PubMed Central

    Perez, Miriam K.; Piedimonte, Giovanni

    2014-01-01

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

  14. Health-Related Quality of Life in Relation to Obesity Grade, Type 2 Diabetes, Metabolic Syndrome and Inflammation

    PubMed Central

    Slagter, Sandra N.; van Vliet-Ostaptchouk, Jana V.; van Beek, André P.; Keers, Joost C.; Lutgers, Helen L.; van der Klauw, Melanie M.; Wolffenbuttel, Bruce H. R.

    2015-01-01

    Background Health-related quality of life (HR-QoL) may be compromised in obese individuals, depending on the presence of other complications. The aim of this study is to assess the effect of obesity-related conditions on HR-QoL. These conditions are i) grade of obesity with and without type 2 diabetes (T2D), ii) metabolic syndrome (MetS), and iii) level of inflammation. Methods From the Dutch LifeLines Cohort Study we included 13,686 obese individuals, aged 18–80 years. HR-QoL was measured with the RAND 36-Item Health Survey which encompasses eight health domains. We calculated the percentage of obese individuals with poor HR-QoL, i.e. those scoring below the domain and sex specific cut-off value derived from the normal weight population. Logistic regression analysis was used to calculate the probability of having poor domain scores according to the conditions under study. Results Higher grades of obesity and the additional presence of T2D were associated with lower HR-QoL, particularly in the domains physical functioning (men: odds ratios (ORs) 1.48–11.34, P<0.005, and women: ORs 1.66–5.05, P<0.001) and general health (men: ORs 1.44–3.07, P<0.005, and women: ORs 1.36–3.73, P<0.001). A higher percentage of obese individuals with MetS had a poor HR-QoL than those without MetS. Furthermore, we observed a linear trend between inflammation and the percentage of obese individuals with poor scores on the HR-QoL domains. Individuals with MetS were more likely to have poor scores in the domains general health, vitality, social functioning and role limitations due to emotional problems. Obese women with increased inflammation levels were more likely to have poor scores on all domains except role limitations due to emotional problems and mental health. Conclusions The impact of obesity on an individual’s quality of life is enhanced by grade of obesity, T2D, MetS and inflammation and are mainly related to reduced physical health. The mental well-being is less

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

    PubMed Central

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

    2016-01-01

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

  16. 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.

  17. The immune system’s involvement in obesity-driven type 2 diabetes

    PubMed Central

    Shu, Chengyi Jenny; Benoist, Christophe; Mathis, Diane

    2012-01-01

    Type 2 diabetes is now a worldwide epidemic, strongly correlated with an elevated incidence of obesity. Obesity-associated adipose tissue inflammation is a major cause of the decreased insulin sensitivity seen in type 2 diabetes. Recent studies have shed light on the crosstalk between the immune system and organismal metabolism. This review discusses the connection between inflammation in adipose tissue and systemic insulin resistance, focusing on the roles of innate and adaptive immune cell subsets in the pathogenesis of this metabolic disease. PMID:23333525

  18. Are epigenetic drugs for diabetes and obesity at our door step?

    PubMed

    Arguelles, Andrix O; Meruvu, Sunitha; Bowman, John D; Choudhury, Mahua

    2016-03-01

    Recent interest in epigenetics has focused on small molecules aimed at modifying disease-specific gene expression, including diabetes and obesity. Several major classes of epigenetic modifier include drugs already in the marketplace as well as several in various stages of study. These classes include histone deacetylase inhibitors (HDACi), histone acetyltransferase inhibitors (HATi), protein arginine methyltransferase inhibitors (PRMTis), DNA methyltransferase inhibitors (DNMTis), histone demethylating inhibitors (HDMis), and sirtuin-activating compounds (STACs). In this review, we discuss drugs with epigenetic properties that have been identified as potential therapeutic agents in the treatment of diabetes and obesity, including those currently in clinical trials.

  19. Dopamine Adaptations as a Common Pathway for Neurocognitive Impairment in Diabetes and Obesity: A Neuropsychological Perspective

    PubMed Central

    Small, Dana M.

    2017-01-01

    Evidence accumulates linking obesity and diabetes with cognitive dysfunction. At present the mechanism(s) underlying these associations and the relative contribution of diet, adiposity, and metabolic dysfunction are unknown. In this perspective key gaps in knowledge are outlined and an initial sketch of a neuropsychological profile is developed that points toward a critical role for dopamine (DA) adaptations in neurocognitive impairment secondary to diabetes and obesity. The precise mechanisms by which diet, metabolic dysfunction, and adiposity influence the DA system to impact cognition remains unclear and is an important direction for future research.

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

    PubMed

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

    2010-12-01

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

  1. Our Health Is in Our Hands: A Social Marketing Campaign to Combat Obesity and Diabetes.

    PubMed

    George, Kimberly S; Roberts, Calpurnyia B; Beasley, Stephen; Fox, Margaretta; Rashied-Henry, Kweli

    2015-05-14

    Purpose . Design, implement, and evaluate a 6-week social marketing campaign (SMC) to raise awareness of obesity and increase involvement in type 2 diabetes prevention, nutrition, and fitness programs offered by the Brooklyn Partnership to Drive Down Diabetes (BP3D) in two low-income, urban communities. Design . This was a nonexperimental, formative research, mixed-methods study. Setting . The study took place in Central Brooklyn and East New York, two of the most impoverished, high-need communities in New York City. Subjects . Participants were black and Hispanic adults, who were 18+ years of age and residing in the priority communities. Intervention . Advertisements in English and Spanish encouraging healthier eating habits and advocating for better food options were displayed on New York City bus shelters, buses, and subway cars operating in the priority communities. Social media, Web sites, and print material were used to promote the campaign message. Measures . Social media metrics and a street intercept postsurvey informed the campaign's success. Analysis . Quantitative data were analyzed using descriptive statistics. Results . One hundred advertisements in English and Spanish were posted. After an 18-month follow-up, there were over 11,000 visits to the Facebook page. Results from the postsurvey (n = 171) suggest the SMC motivated participants who recognized the advertisements to improve their health behaviors. Conclusion . A multifaceted SMC that coincides with prevention programs can effectively raise attention to health issues and activities in a high-risk population at a relatively low cost.

  2. Impact of the Pro12Ala polymorphism of the PPARγ2 gene on diabetes and obesity in a highly consanguineous population

    PubMed Central

    Bener, Abdulbari; Zirie, M; Al-Hamaq, AOAA; Nawaz, Z; Samson, N; Mohammad, R

    2015-01-01

    Background: The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor subfamily of transcription factors. It has been reported that they play important roles in obesity and the development of type 2 diabetes mellitus (T2DM). Materials and Methods: This case-control study was carried out among 764 Qatari patients with diabetes and 764 healthy subjects above 20 years of age at Primary Healthcare Clinics (PHCs) from January 2011 to December 2012. Face-to-face interviews were based on a questionnaire that included variables such as age, sex, sociodemographic status, body mass index (BMI) and other clinical parameters. The Pro12Ala in the PPARγ2 gene was detected on the LightCycler using two specific probes. Univariate and multivariate statistical analysis were performed. Results: The study revealed that in the diabetes group, Pro/(10.2% vs 9.4%; P = 0.606) and Ala/Ala (1.4% vs 0.9%; P = 0.343) were higher than in controls, whereas Pro/Pro (88.4% vs 89.7%;P = 0.413) was lower in diabetes patients, but no significant difference was observed among the genotype groups. In obese patients with diabetes, Pro/Pro (89% vs 89.9%;P = 0.792) and Pro/Ala (8.9% vs 10.1%;P = 0.671) were lower than in obese healthy subjects. No homozygous Ala/Ala was found in obese healthy subjects, whereas 6 Ala/Ala homozygotes were in obese diabetes group. But in diabetes group, obese patients had higher homozygous of Pro/Pro (89.3% vs 87.8%;P = 0.523) and Ala/Ala (1.8% vs 1.2%;P = 0.771) compared to non-obese patients. Conclusion: The current study did not reveal an association between the Pro12Ala polymorphism of the PPAR γ2 gene and type 2 diabetes (T2D) in Qatari's population. PMID:25593831

  3. Development of diabetes in non-obese diabetic mice promotes Chlamydia pneumoniae dissemination from lung to peripheral blood

    PubMed Central

    Yamaguchi, Hiroyuki; Oshio, Ichiro; Osaki, Takako; Kurata, Satoru; Yamamoto, Yoshimasa; Kamiya, Shigeru

    2006-01-01

    We examined a possible association between development of diabetes in non-obese diabetic (NOD) mice and dissemination of Chlamydia (Chlamydophila) pneumoniae from lung to peripheral blood. By real-time reverse transcription-polymerase chain reaction (RT-PCR) with primers for C. pneumoniae 16S rRNA, following multiple intranasal inoculations, we detected bacteria in lung in NOD mice with diabetes (38.5%) as well as Institute of Cancer Research, USA (ICR) mice (40%), but prevalence of bacteria in NOD mice without diabetes (pre-diabetic NOD mice and non-diabetic retired NOD mice) was very low (4.8%). The bacteria were only detected in peripheral blood mononuclear cells (PBMCs) cultured with hydrocortisone of the NOD mice with diabetes (53.8%). Results of immunostaining with fluorescein isothiocyanate-conjugated antichlamydia monoclonal antibody also showed the presence of bacterial antigens in the lungs and the PBMCs judged as positive by the RT-PCR. However, C. pneumoniae from cultured PBMCs of all NOD mice was undetected by cultivation method with inclusion-forming units assay. In addition, no influence of C. pneumoniae intranasal inoculation on development of diabetes in NOD mice was confirmed. Thus, the development of diabetes in NOD mouse appears to be one of critical factors for promoting the dissemination of C. pneumoniae from lung to peripheral blood. PMID:16623756

  4. Knowledge, Attitude and Practice of Type 2 Diabetic Patients Regarding Obesity: Study in a Tertiary Care Hospital in Bangladesh

    PubMed Central

    Mumu, Shirin Jahan; Ara, Ferdous; Ali, Liaquat; Hossain, Sharmin; Ahmed, Kazi Rumana

    2012-01-01

    Prevention and management of obesity largely depends on patient motivation and education and these, in turn, can be greatly facilitated by adequate baseline data on the knowledge, attitude and practice (KAP) of patients. The aim of this study is to assess KAP on obesity among Bangladeshi type 2 diabetics. Under a cross-sectional design 160 type 2 diabetics were selected from outpatient department of Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine & Metabolic Disorders. A standard questionnaire was constructed in local language and interview was administrated. Age and body mass index (BMI) of the respondents were 45.17±5.68 years and 25.6 ±4 kg/m2 respectively. Among them 45% were male, 38% had primary education, 25% belonged to normal weight, 1/2 of them were overweight and rest were obese. KAP score of the respondents was [mean ±SD(%)] 60.03±13.82, 79.30±8.27, 55.50±19.21 respectively. Majority were unaware about ideal body weight, energy requirement and the weight measurement techniques. A substantial proportion of the respondents considered fast food, soft drinks, mayonnaise as healthier food. Majority of them positively agreed on willingness to follow proper diet, maintaining ideal body weight, dietary management and exercise. More than half of the normal weight and overweight respondents did exercise >45 min, while 1/3 obese did not do exercise (35%). KAP score were significantly associated with respondents’ level of education (P=0.0001, P=0.007, P=0.05 respectively) practice score was significantly associated with sex (P=0.0001), occupation (P=0.003) and BMI (P=0.0001). There is a need for increased effort towards developing and making education programs focusing on empowering the persons to transform their knowledge and attitude into practice. PMID:28299081

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

    PubMed Central

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

    2015-01-01

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

  6. Glycemia, diabetes status, and cognition in middle aged Hispanics

    PubMed Central

    Luchsinger, José A.; Cabral, Rafi; Eimicke, Joseph P.; Manly, Jennifer J.; Teresi, Jeanne

    2015-01-01

    Objective To examine the association of glycemia and diabetes status with cognition among 600 Hispanics aged 55 to 64 years from Northern Manhattan. Methods Diabetes was ascertained by history or Hemoglobin A1c (HbA1c). Normal glucose tolerance (NGT) and pre-diabetes were ascertained with HbA1c. Memory was assessed with the Selective Reminding Test (SRT). Executive abilities were assessed using the Color trails 1 and 2, and verbal fluency test. The cross-sectional association of glycemia and diabetes status with cognitive performance was examined using linear regression. Results Participants were a mean age of 59.2 ± 2.9 years old, 76.7% were women, and more than 65% had pre-diabetes or diabetes. HbA1C (β = − 0.97; p <0.001) and diabetes (β = − 2.06; p = 0.001) were related with lower SRT total recall after adjustment for demographics, education, and vascular risk factors. Pre-diabetes was associated with worse performance in color trails 2 (β = − 6.45 p = 0.022) after full adjustment. Conclusions Higher glycemia and diabetes are related to worse memory and executive abilities in late middle age, while pre-diabetes is related only to worse executive abilities. Longitudinal follow-up is needed to understand the order and progression of these deficits. PMID:26163818

  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.

  8. Oxidative stress associated to dysfunctional adipose tissue: a potential link between obesity, type 2 diabetes mellitus and breast cancer.

    PubMed

    Crujeiras, A B; Díaz-Lagares, A; Carreira, M C; Amil, M; Casanueva, F F

    2013-04-01

    Diabetes mellitus and breast cancer are two important health problems. Type 2 diabetes (T2DM) and obesity are closely linked with both being associated with breast cancer. Despite abundant epidemiological data, there is no definitive evidence regarding the mechanisms responsible for this association. The proposed mechanisms by which diabetes affects breast cancer risk and prognosis are the same as the mechanisms hypothesised for the contribution of obesity to breast cancer risk. The obesity-induced inflammation promoted by adipose tissue dysfunction is a key feature, which is thought to be an important link between obesity and cancer. Inflammation induces an increase in free radicals and subsequently promotes oxidative stress, which may create a microenvironment favourable to the tumor development in obese persons. Oxidative stress is also proposed as the link between obesity and diabetes mellitus. Therefore, obesity-related oxidative stress could be a direct cause of neoplastic transformation associated with obesity and T2DM in breast cancer cells. This review is focused on the role of obesity-related oxidative stress in the context of chronic inflammation, on the time of breast cancer onset and progression, which provide targets for preventive and therapeutic strategies in the fields of diabetes and obesity-related breast cancer.

  9. 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

  10. The diabetes-obesity-hypertension nexus in Qatar: evidence from the World Health Survey

    PubMed Central

    2014-01-01

    Background As countries develop economically, an “epidemiological transition” occurs whereby a set of chronic diseases increasingly becomes a country’s health challenge. Against this background, this paper examines the most common conditions associated with the prevalence of diabetes in Qatar, with a specific focus on the diabetes-obesity-hypertension nexus. Methods We analyzed data from the World Health Organization’s World Health Survey conducted in the State of Qatar in 2006. The survey included demographic, anthropometric, and blood chemistry measurements. Using multivariate logistical regression analysis, we assessed the most common conditions associated with diabetes, using both objective and subjective measures of diabetes. The objective measures relied on random blood sugar tests, and the subjective measure included respondents who affirmatively answered the question on diabetes diagnosis. We repeated our analysis on respondents who had blood glucose levels high enough to be considered diabetic/glucose intolerant but did not answer affirmatively on the question of diabetes diagnosis. Results When using the objective measure of diabetes, the following conditions appeared significant: obesity (OR = 1.5, 95% CI = 1.2 – 1.9), higher income (OR = 1.4, 95% CI = 1.0 – 1.9), high cholesterol (OR = 1.4, 95% CI = 1.0 – 1.9), having Qatari origin (OR = 1.3, 95% CI = 1.0 – 1.7), and increasing systolic blood pressure (SBP) 120–139 mmHg (OR = 1.5, 95% CI = 1.2 – 2.0), SBP 140–159 mmHg (OR = 2.2, 95% CI = 1.6 – 3.1), SBP > 160 mmHg (OR = 3.2, 95% CI = 2.0 – 5.3). Similar results were obtained using the subjective measure of diabetes as a dependent variable. When applied to the group of respondents that included pre-diabetics and those who did not know they were diabetic, obesity and hypertension appeared as the only statistically significant explanatory variables. Conclusion High

  11. Rapid Deterioration of Insulin Secretion in Obese Adolescents Preceding the Onset of Type 2 Diabetes

    PubMed Central

    Elder, Deborah A.; Hornung, Lindsey N.; Herbers, Patricia M.; Prigeon, Ron; Woo, Jessica G.; D'Alessio, David A.

    2014-01-01

    Objective To identify pathophysiologic changes that lead to the onset of type 2 diabetes (T2DM) in adolescents. Study design Obese adolescents with NGT (n=41) were studied longitudinally over 4 years with serial measure of the acute insulin response to IV glucose (AIRg) as well as proinsulin (PI) concentrations. Insulin resistance was estimated with HOMA modeling, the disposition index (DI) computed as AIRg × 1/HOMA-IR, and IV glucose tolerance estimated as the glucose disappearance constant (kg). Results Four adolescents developed diabetes during the study (DM), and the rest of the cohort remained non-diabetic (NDM). Baseline PI exceeded the interquartile range of the NDM group in 3 of 4 subjects with DM and all had > 85% reduction from baseline AIRg, and DI, within 6 months of diagnosis. All the subjects with DM gained weight over the course of the study but these changes paralleled those for the NDM group. HOMA-IR increased substantially in 1 of the subjects with DM at the time of diagnosis, but was comparable with baseline in the other 3. The DI and kg of the subjects with DM was below the 10th percentile of the NDM group before and after diagnosis. Conclusion Conversion from NGT to T2DM in adolescents can occur rapidly, and T2DM onset is heralded by a substantial decline in AIRg and DI, as well as increased release of PI. These results support loss of beta-cell function as the proximate step in the development of T2DM in this age group. PMID:25557969

  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. 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…

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

    PubMed

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

    2014-03-01

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

  16. New insights on diabetes mellitus and obesity in Africa-Part 2: prevention, screening and economic burden.

    PubMed

    Kengne, Andre Pascal; Sobngwi, Eugene; Echouffo-Tcheugui, Justin-Basile; Mbanya, Jean-Claude

    2013-08-01

    Evidence has been accumulating on the importance of the rising burden of diabetes mellitus on the African continent at an increasingly higher pace. In the first paper of this series of two companion papers, recent evidence on the prevalence, pathogenesis and comorbidities of obesity and diabetes mellitus in Africa were summarised. In this second paper, we focus on recent developments pertaining to the prevention, screening and the economic burden of diabetes and obesity on the continent. There are indications that awareness on diabetes and chronic diseases at large has increased in Africa in recent times. However, the care for diabetes largely remains suboptimal in most countries, which are not adequately prepared to face the prevention and control of diabetes, as the costs of caring for the condition pose a tremendous challenge to most local economies. Moreover, translation strategies to prevent and control diabetes and obesity, on the continent, are still to be evaluated.

  17. Impact of Restricted Maternal Weight Gain on Fetal Growth and Perinatal Morbidity in Obese Women With Type 2 Diabetes

    PubMed Central

    Ásbjörnsdóttir, Björg; Rasmussen, Signe S.; Kelstrup, Louise; Damm, Peter; Mathiesen, Elisabeth R.

    2013-01-01

    OBJECTIVE Since January 2008, obese women with type 2 diabetes were advised to gain 0–5 kg during pregnancy. The aim with this study was to evaluate fetal growth and perinatal morbidity in relation to gestational weight gain in these women. RESEARCH DESIGN AND METHODS A retrospective cohort comprised the records of 58 singleton pregnancies in obese women (BMI ≥30 kg/m2) with type 2 diabetes giving birth between 2008 and 2011. Birth weight was evaluated by SD z score to adjust for gestational age and sex. RESULTS Seventeen women (29%) gained ≤5 kg, and the remaining 41 gained >5 kg. The median (range) gestational weight gains were 3.7 kg (−4.7 to 5 kg) and 12.1 kg (5.5–25.5 kg), respectively. Prepregnancy BMI was 33.5 kg/m2 (30–53 kg/m2) vs. 36.8 kg/m2 (30–48 kg/m2), P = 0.037, and median HbA1c was 6.7% at first visit in both groups and decreased to 5.7 and 6.0%, P = 0.620, in late pregnancy, respectively. Gestational weight gain ≤5 kg was associated with lower birth weight z score (P = 0.008), lower rates of large-for-gestational-age (LGA) infants (12 vs. 39%, P = 0.041), delivery closer to term (268 vs. 262 days, P = 0.039), and less perinatal morbidity (35 vs. 71%, P = 0.024) compared with pregnancies with maternal weight gain >5 kg. CONCLUSIONS In this pilot study in obese women with type 2 diabetes, maternal gestational weight gain ≤5 kg was associated with a more proportionate birth weight and less perinatal morbidity. PMID:23248191

  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.

  19. Exploring the role of BCHE in the onset of Diabetes, Obesity and Neurological Disorders.

    PubMed

    Rao, Allam Appa; Jyothsna, Gundlapally; Shalini, Pulipati; Kumar, Amit; Bhattacharya, Anupam; Kashyap, Amita

    2012-01-01

    Diabetes, Obesity and Neurological disturbances, most often show co-occurrence. There has been an extensive research in this domain, but the exact mechanism underlying the co-occurrence of the three conditions is still an enigma. The current paper is an approach to establish the role of Butyryl cholinesterase (BCHE) in Diabetes, Obesity and Neurological disorders by performing a comparative analysis with Neuroligin (NLGN2) a protein belonging to the same family. BCHE has its role in glucose regulation, Lipid metabolism and nerve signaling. Emphasis is laid on BCHE's diverse functions whose impediment affects the above mentioned metabolic pathways. Insilco techniques were employed to analyze the sequence, structural and functional similarities of the two proteins. A point mutation is focused which is common to both BCHE and Neuroligin. The mutation occurs at the homologous position in both the proteins making them deficient. This affects the three metabolic pathways leading to the respective disorders. The work describes the pathway that describes the role of BCHE in the onset of obesity mediated diabetes. The pathway further explains the association between Diabetes, Obesity and neurological disturbances.

  20. 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…

  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. 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 ...

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

    PubMed

    Yoshinari, Orie; Shiojima, Yoshiaki; Igarashi, Kiharu

    2012-10-22

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

  4. 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...

  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 Central

    2015-01-01

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

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

    PubMed

    Friedman, Jacob E

    2015-08-01

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

  7. 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.

  8. A Randomized Study on the Effect of Weight Loss on Obstructive Sleep Apnea Among Obese Patients With Type 2 Diabetes

    PubMed Central

    Foster, Gary D.; Borradaile, Kelley E.; Sanders, Mark H.; Millman, Richard; Zammit, Gary; Newman, Anne B.; Wadden, Thomas A.; Kelley, David; Wing, Rena R.; Pi-Sunyer, F. Xavier; Reboussin, David; Kuna, Samuel T.

    2010-01-01

    Background The belief that weight loss improves obstructive sleep apnea (OSA) has limited empirical support. The purpose of this 4-center study was to assess the effects of weight loss on OSA over a 1-year period. Methods The study included 264 participants with type 2 diabetes and a mean (SD) age of 61.2 (6.5) years, weight of 102.4 (18.3) kg, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 36.7 (5.7), and an apnea-hypopnea index (AHI) of 23.2 (16.5) events per hour. The participants were randomly assigned to either a behavioral weight loss program developed specifically for obese patients with type 2 diabetes (intensive lifestyle intervention [ILI]) or 3 group sessions related to effective diabetes management (diabetes support and education [DSE]). Results The ILI participants lost more weight at 1 year than did DSE participants (10.8 kg vs 0.6 kg; P < .00l). Relative to the DSE group, the ILI intervention was associated with an adjusted (SE) decrease in AHI of 9.7 (2.0) events per hour (P < .001). At 1 year, more than 3 times as many participants in the ILI group than in the DSE group had total remission of their OSA, and the prevalence of severe OSA among ILI participants was half that of the DSE group. Initial AHI and weight loss were the strongest predictors of changes in AHI at 1 year (P<.01). Participants with a weight loss of 10 kg or more had the greatest reductions in AHI. Conclusions Physicians and their patients can expect that weight loss will result in significant and clinically relevant improvements in OSA among obese patients with type 2 diabetes. Trial Registration clinicaltrials.gov Identifier: NCT00194259 PMID:19786682

  9. Investigating parent of origin effects in studies of Type 2 Diabetes and Obesity

    PubMed Central

    Rampersaud, Evadnie; Mitchell, Braxton D.; Naj, Adam C.; Pollin, Toni I.

    2010-01-01

    The role of parent-of-origin effects (POE) in the etiology of complex diseases such as type 2 diabetes (T2DM) and obesity is currently of intense interest, but still largely unclear. POE are transmittable genetic effects whereby the expression of the phenotype in the offspring depends upon whether the transmission originated from the mother or father. In mammals, POE can be caused by genetic imprinting, intrauterine effects, or maternally inherited mitochondrial genes. In this paper, we describe the different mechanisms underlying POE, characterize known examples of POE in rare forms of diabetes, and review the evidence from linkage and association studies for POE in T2DM and obesity. Finally, we summarize some of the new and established statistical and experimental approaches commonly used to detect POE. Through this paper, we hope emphasizes the potentially significant importance of POE in the etiology of T2DM and obesity. PMID:18991601

  10. 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

  11. [Cardiometabolic effects of rimonabant in obese/overweight subjects with dyslipidaemia or type 2 diabetes].

    PubMed

    Scheen, A J; Van Gaal, L F

    2007-02-01

    Rimonabant (Acomplia) is the first selective CB1 receptor blocker of the endocannabinoid system. It has been evaluated in the RIO ("Rimonabant In Obesity and related disorders") programme including above 6.600 overweight/obese patients with or without comorbidities followed for 1 to 2 years. Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. In patients with type 2 diabetes, rimonabant also diminishes HbA1c levels, an effect confirmed in the recent SERENADE trial. Almost half of the metabolic effects occurs beyond weight loss, suggesting direct peripheral effects of rimonabant. Rimonabant is indicated in Europe as an adjunct to diet and exercise for the treatment of obese patients, or overweight patients with associated risk factor(s), such as type 2 diabetes or dyslipidaemia.

  12. Dynamics of Diabetes and Obesity: An Alarming Situation in the Developing Countries in Asia.

    PubMed

    Chakraborty, Chiranjib; Das, Srijit

    2016-01-01

    The incidence of diabetes in developing countries in Asia has increased over the last few years. The economic development is radically changing the lifestyle of the younger generation who prefer to embrace the western lifestyle of eating high calorie fast food with minimal physical exercise. Previously, the rate of diabetes was very low but it is increasing at an alarming rate in the developing countries in Asia. Admittedly, there is paucity of literature on the prevalence of patients with type-1 diabetes in Asian developing countries due to lower field surveys and lack of quantitative data. Few contributing factors such as body mass index (BMI) and its relation with obesity and diabetes, energy dense diet, excessive caloric intake, sedentary behaviors, lifestyle and family history, gene and genomewide association of diabetes, genes and gene polymorphisms are being discussed especially with regard to the Asian population. Dynamics of the diabetes and obesity was depicted for the population of Asian developing countries with special emphasis on China and India. Diabetes has become widespread among the low-income communities. Hence, it is necessary to develop appropriate healthcare policies in order to mitigate this rampant epidemic before it is too late.

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

    PubMed

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

    2016-02-19

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

  14. 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

  15. 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.

  16. [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.

  17. 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

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

    PubMed Central

    Surani, Salim R

    2014-01-01

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

  19. A peroxisome proliferator-activated receptor gamma agonist influenced daily profile of energy expenditure in genetically obese diabetic rats.

    PubMed

    Yoshida, Yuki; Ichikawa, Mineko; Ohta, Minoru; Kanai, Setsuko; Kobayash, Mikako; Ichimaru, Yuhei; Shimazoe, Takao; Watanabe, Shigenori; Funakoshi, Akihiro; Miyasak, Kyoko

    2002-03-01

    Otsuka Long Evans Tokushima Fatty (OLETF) rats were developed as a model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity. We reported that the daily profiles of energy expenditure associated with two peaks (one between 05:00 and 08:00 and the other between 20:00 and 22:00) were observed at 8 weeks of age (without NIDDM), while these two peaks disappeared at 24 weeks of age with NIDDM. As a new anti-diabetic drug, a peroxisome proliferator-activated receptor y agonist pioglitazone hydrochloride has been developed, we examined whether pioglitazone normalized daily profiles of energy expenditure at 24 weeks of age. A control diet and pioglitazone (0.1%)-containing diet were fed from 6 weeks of age. The two peaks of daily profiles of energy expenditure, which disappeared in OLETF rats with the control diet at 24 weeks of age, were reproduced by administration of pioglitazone. The respiratory quotient was lower and fat derived energy used for combustion was increased by pioglitazone at both ages. The body weight, daily food intake, plasma levels of fat, insulin, leptin and the wet weight of visceral fat were not influenced, but the levels of blood hemoglobin Alc and plasma tumor necrosis factor a were decreased by pioglitazone. Administration of pioglitazone improved daily profiles of energy expenditure via affecting glucose and fat metabolisms.

  20. Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody.

    PubMed

    Weiss, L; Slavin, S; Reich, S; Cohen, P; Shuster, S; Stern, R; Kaganovsky, E; Okon, E; Rubinstein, A M; Naor, D

    2000-01-04

    Inflammatory destruction of insulin-producing beta cells in the pancreatic islets is the hallmark of insulin-dependent diabetes mellitus, a spontaneous autoimmune disease of non-obese diabetic mice resembling human juvenile (type I) diabetes. Histochemical analysis of diabetic pancreata revealed that mononuclear cells infiltrating the islets and causing autoimmune insulitis, as well as local islet cells, express the CD44 receptor; hyaluronic acid, the principal ligand of CD44, is detected in the islet periphery and islet endothelium. Injection of anti-CD44 mAb 1 hr before cell transfer of diabetogenic splenocytes and subsequently on alternate days for 4 weeks induced considerable resistance to diabetes in recipient mice, reflected by reduced insulitis. Contact sensitivity to oxazolone was not influenced by this treatment. A similar antidiabetic effect was observed even when the anti-CD44 mAb administration was initiated at the time of disease onset: i.e., 4-7 weeks after cell transfer. Administration of the enzyme hyaluronidase also induced appreciable resistance to insulin-dependent diabetes mellitus, suggesting that the CD44-hyaluronic acid interaction is involved in the development of the disease. These findings demonstrate that CD44-positive inflammatory cells may be a potential therapeutic target in insulin-dependent diabetes.

  1. Prevalence of the metabolic syndrome among Korean adults using the new International Diabetes Federation definition and the new abdominal obesity criteria for the Korean people.

    PubMed

    Kim, Hee Man; Kim, Dae Jung; Jung, In Hyun; Park, Chanwang; Park, Jong

    2007-07-01

    This study was performed to compare the prevalence of the metabolic syndrome according to the International Diabetes Federation (IDF) and National Cholesterol Education Program (NCEP) definitions, and abdominal obesity criteria of WHO and the Korean Society for the Study of Obesity (KSSO) in Korean adults. A total of 4452 adults aged > or =20 years from the Korean National Health and Nutrition Examination Survey 2001 were analyzed. The prevalence of the metabolic syndrome estimated by NCEP definition with WHO criteria, NCEP with KSSO, IDF with WHO, and IDF with KSSO were 26.7%, 23.7%, 23.8% and 17.5%, respectively. The agreement percent among the four definitions ranged from 88.7% to 100% in men, and from 85.6% to 94.9% in women. The NCEP-defined metabolic syndrome was more strongly associated with hypertension and diabetes than the IDF-defined metabolic syndrome (age-adjusted odds ratio: 5.1 versus 3.6 for hypertension and 6.4 versus 3.2 for diabetes in men, respectively; 5.4 versus 3.4-4.3 for hypertension and 11.1 versus 3.8-4.2 for diabetes in women, respectively). Both definitions of the metabolic syndrome were associated with coronary heart disease or stroke only in women. Prospective studies are warranted to evaluate the predictive ability of the new definition of the metabolic syndrome and the new criteria of abdominal obesity for cardiovascular morbidity and mortality in Korean adults.

  2. Cardiometabolic Risk Factors Among 1.3 Million Adults With Overweight or Obesity, but Not Diabetes, in 10 Geographically Diverse Regions of the United States, 2012–2013

    PubMed Central

    Horberg, Michael; Koebnick, Corinna; Young, Deborah Rohm; Waitzfelder, Beth; Sherwood, Nancy E.; Daley, Matthew F.; Ferrara, Assiamira

    2017-01-01

    Introduction Various phenotypes of overweight and obesity pose various health risks. The objective of this study was to determine the prevalence of 4 commonly measured cardiometabolic risk factors (CRFs) among adults with overweight or obesity, but not diabetes, at the time of the study. Methods We analyzed data for 1,294,174 adults (aged ≥20 y) who were members of one of 4 integrated health systems. Each cohort member had a body mass index in 2012 or 2013 that indicated overweight or obesity. We determined the presence of 4 CRFs within 1 year of the first BMI measurement: elevated blood pressure (systolic ≥130 mm Hg or diastolic >85 mm Hg or ICD-9-CM [International Classification of Diseases, Ninth Revision, Clinical Modification] diagnosis code 401.0–405.9); elevated triglycerides (≥150 mg/dL or ICD-9-CM 272.1); low high-density lipoprotein cholesterol (<40 mg/dL for men or <50 mg/dL for women or ICD-9-CM 272.5); and prediabetes (fasting glucose 100–125 mg/dL or HbA1c 5.7%–6.4% or ICD-9-CM 790.2x). We tested the risk of having 1 or more CRFs after adjusting for obesity class and demographic characteristics with multivariable logistic regression. Results Among participants with overweight (52.5% of the sample), 18.6% had none of the 4 CRFs. Among the 47.5% of participants with obesity, 9.6% had none; among participants with morbid obesity, 5.8% had none. Age was strongly associated with CRFs in multivariable analysis. Conclusion Almost 10% of participants with obesity had no CRFs. Overweight or obesity increases cardiometabolic risk, but the number and type of CRFs varied substantially by age, even among participants with morbid obesity. PMID:28278130

  3. 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.

  4. Epigenetic modifications in adipose tissue – relation to obesity and diabetes

    PubMed Central

    Kasinska, Marta A.; Sliwinska, Agnieszka

    2015-01-01

    The growing number of people suffering from obesity and type 2 diabetes mellitus (T2DM) is a global health problem that results in increased mortality from their complications, mainly cardiovascular diseases. Although the relationship between obesity and T2DM is well established, the common molecular pathomechanisms are still under investigation. Recently, it has been suggested that epigenetic modifications may be involved in both obesity and T2DM development. Epigenetics plays a pivotal role in the regulation of gene expression by the reversible modifications of chromatin structure without any changes in DNA sequence. Epigenetic modifications include DNA methylation, posttranslational histone modifications and miRNA interference. Therefore, the aim of this article is to discuss the current knowledge on epigenetic modifications in adipose tissue and their association with obesity and T2DM. PMID:27904521

  5. Vitamin D status and circulating biomarkers of endothelial dysfunction and inflammation in non-diabetic obese individuals: a pilot study

    PubMed Central

    Stokić, Edita; Stošić, Zoran; Kojić, Nevena Eremić; Katsiki, Niki; Mikhailidis, Dimitri P.; Isenovic, Esma R.

    2016-01-01

    Introduction Obesity and inadequate vitamin D status are associated with endothelial dysfunction and cardiovascular disease. We evaluated the associations between vitamin D status (i.e. serum levels of 25-hydroxyvitamin D (25(OH)D)), biomarkers of endothelial dysfunction (i.e. serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble E-selectin (sE-selectin)), inflammatory markers (i.e. high-sensitivity C-reactive protein (hsCRP) and fibrinogen) and cardiometabolic risk factors. Material and methods Fifty obese (body mass index (BMI) ≥ 30 kg/m2) non-diabetic adults (mean age: 36.2 ±5.4 years) without pre-existing cardiovascular abnormalities and 25 clinically healthy, normal weight and age-matched individuals were included. Anthropometric parameters, markers of glucose and lipid metabolism, and serum levels of inflammatory and endothelial dysfunction biomarkers were assessed in all subjects. Results The mean serum 25(OH)D level was significantly lower in the obese group than in controls (33.5 ±15.2 vs. 60.1 ±23.1 nmol/l; p < 0.001). In the obese group, sE-selectin (36.4 (32.1–47.2) vs. 32.4 (24.6–35.5) ng/ml, p < 0.05) and hsCRP (6.0 ±3.4 vs. 3.5 ±1.0 mg/l, p < 0.05) were significantly higher in individuals with lower than median vitamin D levels (i.e. 31 nmol/l) compared with those with higher vitamin D levels. In multivariable linear regression analysis, hsCRP (β = –0.43; p < 0.001) and sE-selectin (β = –0.30; p = 0.03) were independently and significantly associated with serum 25(OH)D levels in the obese group. Conclusions Vitamin D levels may be related to increased levels of biomarkers of endothelial dysfunction and inflammation in obese non-diabetic individuals. PMID:28144255

  6. Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial

    PubMed Central

    Sadiya, A; Ahmed, S M; Carlsson, M; Tesfa, Y; George, M; Ali, S H; Siddieg, H H; Abusnana, S

    2015-01-01

    Objectives: To study the effect of Vitamin D3 supplementation on metabolic control in an obese type 2 diabetes Emirati population. Methods: This randomized double-blind clinical trial was conducted with 87 vitamin D-deficient obese, type 2 diabetic participants. The vitamin D-group (n=45) and the placebo group (n=42) were matched for gender, age, HbA1c and 25-hydroxy vitamin D (25(OH) D) at the baseline. The study was divided into two phases of 3 months each; in phase 1, the vitamin D-group received 6000 IU vitamin D3/day followed by 3000 IU vitamin D3/day in phase 2, whereas the placebo group (n=42) received matching placebo. Results: After supplementation, serum 25(OH) D peaked in the vitamin D-group in phase 1 (77.2±30.1 nmol/l, P=0.003) followed by a decrease in the phase 2 (61.4±18.8 nmol/l, P=0.006), although this was higher compared with baseline. In the placebo group, no difference was observed in the serum 25(OH) D levels throughout the intervention. Relative to baseline serum, parathyroid hormone decreased 24% (P=0.003) in the vitamin D-group in phase 2, but remained unchanged in the placebo group. No significant changes were observed in blood pressure, fasting blood glucose, HbA1c, C-peptide, creatinine, phosphorous, alkaline phosphatase, lipids, C-reactive protein or thyroid stimulating hormone concentrations compared with baseline in either group. Conclusions: Six months of vitamin D3 supplementation to vitamin D-deficient obese type 2 diabetes patients in the UAE normalized the vitamin D status and reduced the incidence of eucalcemic parathyroid hormone elevation but showed no effect on the metabolic control. PMID:25406966

  7. 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

  8. Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells

    PubMed Central

    Garcia, MM; Fandel, TM; Lin, G; Shindel, AW; Banie, L; Lin, CS; Lue, TF

    2010-01-01

    Introduction Impotence, or erectile dysfunction (ED), is a major complication of type-II diabetes, and many diabetic men with ED are refractory to common ED therapies. Aim To determine whether autologous adipose tissue derived stem cells (ADSC) injected into the penis of impotent obese type-II diabetic rats survive and improve erectile function. Main outcome measures Intracorporal pressure (ICP) increase with cavernous nerve (CN) electrostimulation, immunohistochemistry, real-time PCR, and serum glucose and testosterone assays. Methods Twenty-two 10-week old male fatty type-II diabetic ZDF rats underwent weight and blood glucose measurement every 2 weeks. At age 22 weeks, all animals underwent unilateral CN electrostimulation and ICP measurement to confirm impotence, and paragonadal adipose tissue (5 grams) was harvested and digested to yield 1.5 million ADSC. Impotent animals were randomized to ADSC treatment and sham control groups. At age 23 weeks, treatment group animals underwent penile injection of 1.5 million ADSC; control group animals received only PBS. Erectile function studies were repeated at age 26 weeks, followed by harvest of tissue and serum. Results Pre- and post-treatment stimulation ICP increase was significantly different between groups (p<0.002). In the control group, mean (SD) pre- and post-treatment stimulation ICP increase was 33.8 (15.9) and 31.4 (24.3) cmH2O, respectively, whereas in the treatment group they were 27.4 (14.8) and 65.3 (15.4) cmH2O. BrdU-labeled ADSC were observed within corporal tissue of the treatment group. TUNEL staining (p<0.0001) and caspase-3 m-RNA expression (p<0.05) were significantly higher within corporal tissue of control group versus treatment group animals. Conclusion Autologous ADSCs injected into the penis appear to survive and improve erectile function. Autologous ADSC therapy is a promising approach to treat diabetic impotence. PMID:20104670

  9. Profiling peripheral microRNAs in obesity and type 2 diabetes mellitus.

    PubMed

    Wu, Liangping; Dai, Xiaojiang; Zhan, Junfang; Zhang, Yuxin; Zhang, Hongbin; Zhang, Hongbing; Zeng, Songhua; Xi, Wenbin

    2015-07-01

    Mechanisms of type 2 diabetes mellitus (T2DM) remain elusive, in which obesity (OB) is considered as one of the major risk factors for the disease. A microRNA (miRNA) is a small non-coding RNA molecule functioning in RNA silencing and post-transcriptional regulation of gene expression. It has been demonstrated that some miRNAs can exist in serum stably and is closely related to various diseases. The goal of our study was to identify whether the deregulation of serum miRNAs was associated with T2DM and obesity. Twenty-five subjects with T2DM2, 25 healthy controls, 25 subjects with obesity, and 25 subjects with T2DM combined with obesity were included in the study. A total of 536 miRNA serum samples from these four groups were studied by miRNA polymerase chain reaction (PCR) panels. Data showed that miR-152 and miR-17 were significantly elevated in the OB group, whereas miR-138 was significantly decreased in OB group when compared to controls, T2DM, or T2DM+obesity group. In addition, level of MiR-593 was significantly lower in T2DM group and T2DM+obesity group when compared with controls. Further analysis revealed that the four miRNAs can be used as potential biomarkers to distinguish obesity from T2DM, OB+T2DM, and healthy subjects. Our study is one of the pioneer studies showing the differences in peripheral miRNA level in obesity, T2DM and T2DM combined with obesity. The study results suggest the potential utility of miRNAs in the prediction for obesity and T2DM.

  10. Onset Age of Obesity and Variables of Personality and Biography.

    ERIC Educational Resources Information Center

    Steinberg, Carol

    Three hypotheses derived from Hilde Bruch's formulations regarding onset differences among the obese were tested. In Bruch's theory, adult-onset, or reactive, obesity is a result of psychological trauma; the individual uses eating as a defense against anxiety and depression. Child-onset, or developmental, obesity results from a mixture of…

  11. The effect of exercise on obesity, body fat distribution and risk for type 2 diabetes.

    PubMed

    Goedecke, Julia H; Micklesfield, Lisa K

    2014-01-01

    It is well known that obesity is a major risk factor for type 2 diabetes (T2D), while exercise is known to reduce body fatness and attenuate the risk of T2D. The aim of this chapter is to examine the interactions between exercise, obesity and body fat distribution, and the risk for T2D. Firstly, we show that body fatness, in particular visceral adipose tissue (VAT) accumulation, is associated with insulin resistance and incident T2D. We then show that aerobic exercise of sufficient intensity and volume results in a decrease in body fat and VAT. Conversely, sedentary behavior and physical inactivity are associated with increased body fat and VAT. Finally, the chapter examines the interaction between physical activity (PA), obesity and risk for T2D and shows that both obesity and PA are significant independent predictors of incident T2D, but the magnitude of risk imparted by high levels of body fat is much greater than that of low levels of PA. Further, we show that obese physically active individuals are at greater risk for incident T2D than normal-weight physically inactive individuals. The mechanisms underlying this complex interaction include the ability of exercise to increase free fatty acid oxidation to match high rates of lipolysis associated with obesity, as well as the effects of exercise on adipokine, cytokine and myokine secretion. Exercise, of sufficient volume and intensity, is therefore recommended to reduce obesity, centralization of body fat, and risk of T2D.

  12. Association between obesity and femoral neck strength according to age, sex, and fat distribution.

    PubMed

    Kim, H; Lee, S H; Kim, B J; Koh, J M

    2017-03-29

    Indicators of total and abdominal obesity were negatively associated with femoral neck strength indices. There are age-, sex-, and fat distribution-specific differences in the magnitude of these associations. These suggested that indicators of obesity with different magnitude according to age, sex, and fat distribution associated with poor bone health.

  13. 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

  14. 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

    2016-06-14

    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.

  15. Inhibition of RXR and PPARγ ameliorates diet-induced obesity and type 2 diabetes

    PubMed Central

    Yamauchi, Toshimasa; Waki, Hironori; Kamon, Junji; Murakami, Koji; Motojima, Kiyoto; Komeda, Kajuro; Miki, Hiroshi; Kubota, Naoto; Terauchi, Yasuo; Tsuchida, Atsuko; Tsuboyama-Kasaoka, Nobuyo; Yamauchi, Naoko; Ide, Tomohiro; Hori, Wataru; Kato, Shigeaki; Fukayama, Masashi; Akanuma, Yasuo; Ezaki, Osamu; Itai, Akiko; Nagai, Ryozo; Kimura, Satoshi; Tobe, Kazuyuki; Kagechika, Hiroyuki; Shudo, Koichi; Kadowaki, Takashi

    2001-01-01

    PPARγ is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of PPARγ by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPARγ activity observed in heterozygous PPARγ-deficient mice or the Pro12Ala polymorphism in human PPARγ, has been shown to prevent insulin resistance and obesity induced by a high-fat diet. In this study, we investigated whether functional antagonism toward PPARγ/RXR could be used to treat obesity and type 2 diabetes. We show herein that an RXR antagonist and a PPARγ antagonist decrease triglyceride (TG) content in white adipose tissue, skeletal muscle, and liver. These inhibitors potentiated leptin’s effects and increased fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance. Paradoxically, treatment of heterozygous PPARγ-deficient mice with an RXR antagonist or a PPARγ antagonist depletes white adipose tissue and markedly decreases leptin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance. Our data suggested that appropriate functional antagonism of PPARγ/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes. PMID:11581301

  16. Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes.

    PubMed

    Yamauchi, T; Waki, H; Kamon, J; Murakami, K; Motojima, K; Komeda, K; Miki, H; Kubota, N; Terauchi, Y; Tsuchida, A; Tsuboyama-Kasaoka, N; Yamauchi, N; Ide, T; Hori, W; Kato, S; Fukayama, M; Akanuma, Y; Ezaki, O; Itai, A; Nagai, R; Kimura, S; Tobe, K; Kagechika, H; Shudo, K; Kadowaki, T

    2001-10-01

    PPARgamma is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of PPARgamma by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPARgamma activity observed in heterozygous PPARgamma-deficient mice or the Pro12Ala polymorphism in human PPARgamma, has been shown to prevent insulin resistance and obesity induced by a high-fat diet. In this study, we investigated whether functional antagonism toward PPARgamma/RXR could be used to treat obesity and type 2 diabetes. We show herein that an RXR antagonist and a PPARgamma antagonist decrease triglyceride (TG) content in white adipose tissue, skeletal muscle, and liver. These inhibitors potentiated leptin's effects and increased fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance. Paradoxically, treatment of heterozygous PPARgamma-deficient mice with an RXR antagonist or a PPARgamma antagonist depletes white adipose tissue and markedly decreases leptin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance. Our data suggested that appropriate functional antagonism of PPARgamma/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes.

  17. Glucolipotoxicity diminishes cardiomyocyte TFEB and inhibits lysosomal autophagy during obesity and diabetes.

    PubMed

    Trivedi, Purvi C; Bartlett, Jordan J; Perez, Lester J; Brunt, Keith R; Legare, Jean Francois; Hassan, Ansar; Kienesberger, Petra C; Pulinilkunnil, Thomas

    2016-12-01

    Impaired cardiac metabolism in the obese and diabetic heart leads to glucolipotoxicity and ensuing cardiomyopathy. Glucolipotoxicity causes cardiomyocyte injury by increasing energy insufficiency, impairing proteasomal-mediated protein degradation and inducing apoptosis. Proteasome-evading proteins are degraded by autophagy in the lysosome, whose metabolism and function are regulated by master regulator transcription factor EB (TFEB). Limited studies have examined the impact of glucolipotoxicity on intra-lysosomal signaling proteins and their regulators. By utilizing a mouse model of diet-induced obesity, type-1 diabetes (Akita) and ex-vivo model of glucolipotoxicity (H9C2 cells and NRCM, neonatal rat cardiomyocyte), we examined whether glucolipotoxicity negatively targets TFEB and lysosomal proteins to dysregulate autophagy and cause cardiac injury. Despite differential effects of obesity and diabetes on LC3B-II, expression of proteins facilitating autophagosomal clearance such as TFEB, LAMP-2A, Hsc70 and Hsp90 were decreased in the obese and diabetic heart. In-vivo data was recapitulated in H9C2 and NRCM cells, which exhibited impaired autophagic flux and reduced TFEB content when exposed to a glucolipotoxic milieu. Notably, overloading myocytes with a saturated fatty acid (palmitate) but not an unsaturated fatty acid (oleate) depleted cellular TFEB and suppressed autophagy, suggesting a fatty acid specific regulation of TFEB and autophagy in the cardiomyocyte. The effect of glucolipotoxicity to reduce TFEB content was also confirmed in heart tissue from patients with Class-I obesity. Therefore, during glucolipotoxicity, suppression of lysosomal autophagy was associated with reduced lysosomal content, decreased cathepsin-B activity and diminished cellular TFEB content likely rendering myocytes susceptible to cardiac injury.

  18. 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.

  19. Association of obesity with diabetic retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS Report no. 8).

    PubMed

    Raman, Rajiv; Rani, Padmaja Kumari; Gnanamoorthy, Perumal; Sudhir, R R; Kumaramanikavel, Govindasamy; Sharma, Tarun

    2010-09-01

    The aim of the study was to report the prevalence of obesity indices in individuals with diabetes and find out their association with diabetic retinopathy in the urban Indian population. Subjects (n = 1,414) were recruited from Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetics Study (SN-DREAMS-I), a cross-sectional study between 2003 and 2006. Anthropometric measurements were carried out, and all patients' fundi were photographed using 45 degrees four-field stereoscopic digital photography. The diagnosis of diabetic retinopathy was based on the modified Klein classification. Generalized obesity and abdominal obesity were defined using WHO Asia Pacific guidelines with the BMI (body mass index) cutoff as > or =23 kg/m(2), WC (waist circumference) cutoffs as > or =90 cm in men and > or =80 cm in women and WHO guidelines using WHR (waist-to-hip ratio) cutoffs as > or =0.90 for men and > or =0.85 for women. Prevalence of obesity defined by BMI and WC was more in women compared to men, and that defined by WHR was more in men compared to women (P < 0.001). The prevalence of isolated generalized obesity, isolated abdominal obesity and combined obesity were 5.4, 10.1 and 58% in men and 4.5, 10.8 and 74.4% in women, respectively. The prevalence of any diabetic retinopathy and sight-threatening diabetic retinopathy was more in the isolated abdominal obesity group (26.35 and 6.08%, respectively) than in other subgroups. On logistic regression analysis, isolated abdominal obesity (OR 2.02, 95% CI: 1.06-3.86) and increased WHR in women (OR 1.48 95% CI: 1.10-2.38) were associated with diabetic retinopathy; BMI > or = 23 (OR 0.66, 95% CI: 0.48-0.90) and combined obesity (OR 0.72, 95% CI: 0.53-0.99) had a protective role for any diabetic retinopathy in the overall group. In the urban south Indian population, isolated abdominal obesity and higher WHR in women were associated with diabetic retinopathy, but not with the severity of diabetic retinopathy.

  20. The effects of a commercially available weight loss program among obese patients with type 2 diabetes: a randomized study.

    PubMed

    Foster, Gary D; Borradaile, Kelley E; Vander Veur, Stephanie S; Leh Shantz, Kerri; Dilks, Rebecca J; Goldbacher, Edie M; Oliver, Tracy L; Lagrotte, Caitlin A; Homko, Carol; Satz, Wayne

    2009-09-01

    The purpose of this study was to assess the effects of a commercially available weight loss program on weight and glycemic control among obese patients with type 2 diabetes. Participants included 69 patients (49 females, 20 males) with type 2 diabetes who had a mean +/- SD age of 52.2 +/- 9.5 years, a body mass index of 39.0 +/- 6.2 kg/m(2), and hemoglobin A1c (HbA1c) of 7.5 +/- 1.6%. Over half (52.2%) of the participants were African American. Participants were randomly assigned to: 1) a portion-controlled diet (NutriSystem D) (PCD) or 2) a diabetes support and education (DSE) program. After the initial 3 months, the PCD group continued on the PCD for the remaining 3 months, and the DSE group crossed over to PCD for the remaining 3 months. The primary comparison for this study was at 3 months. At 3 months, the PCD group lost significantly more weight (7.1 +/- 4%) than the DSE group (0.4 +/- 2.3%) (P < 0.0001). From 3 to 6 months the change in weight for both groups was statistically significant. After 3 months, the PCD group had greater reductions in HbA1c than the DSE group (-0.88 +/- 1.1 vs 0.03 +/- 1.09; P < 0.001). From 3 to 6 months the PCD group had no further change in HbA1c, while the DSE group showed a significant reduction. These data suggest that obese patients with type 2 diabetes will experience significant improvements in weight, glycemic control, and cardiovascular disease risk factors after the use of a commercially available weight management program.

  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. VGF Peptide Profiles in Type 2 Diabetic Patients’ Plasma and in Obese Mice

    PubMed Central

    D’Amato, Filomena; Noli, Barbara; Angioni, Laura; Cossu, Efisio; Incani, Michela; Messana, Irene; Manconi, Barbara; Solinas, Paola; Isola, Raffaella; Mariotti, Stefano; Ferri, Gian-Luca; Cocco, Cristina

    2015-01-01

    To address the possible involvement of VGF peptides in obesity and diabetes, we studied type 2 diabetes (T2D) and obese patients, and high-fat diet induced obese mice. Two VGF peptides (NAPP-19 and QQET-30) were identified in human plasma by HPLC-ESI-MS. The VGF C-terminus, the above two cleaved peptides, and the TLQP-21 related peptide/s were studied using ELISA and immunohistochemistry. In euglycemic patients, plasma NAPPE and TLQP like peptides were significantly reduced with obesity (74±10 vs. 167±28, and 92±10 vs. 191±19 pmol/ml, mean+SEM, n = 10 and 6, obese vs. normal BMI, respectively, p<0.03). Upon a standard glucose load, a distinct response was shown for VGF C-terminus, TLQP and QQET-like (ERVW immunoreactive) peptides in euglycemic normal BMI patients, but was virtually abolished in euglycemic obese, and in T2D patients independently of BMI. High-fat diet induced obese mice showed reduced plasma VGF C-terminus, NAPPE and QQET-like (ERVW) peptide/s (3±0.2 vs. 4.6±0.3, 22±3.5 vs. 34±1.3, and 48±7 vs. 100±7 pmol/ml, mean+SEM, n = 8/group, obese vs. slim, respectively, p<0.03), with a loss of the response to glucose for all VGF peptides studied. In immunohistochemistry, TLQP and/or VGF C-terminus antibodies labelled VGF containing perikarya in mouse celiac ganglia, pancreatic islet cells and thin beaded nerve fibres in brown adipose tissues, with fewer in white adipose tissue. Upon the glucose load, tyrosine hydroxylase and VGF C-terminus immunoreactive axons became apparent in pancreatic islets of slim animals, but not in obese animals. Alltogether, a significant loss of VGF peptide immunoreactivity and/or their response to glucose was demonstrated in obese patients, with or without T2D, in parallel with a similar loss in high-fat diet induced obese mice. An involvement of VGF in metabolic regulations, including those of brown and/or white adipose tissues is underlined, and may point out specific VGF peptides as potential targets for diagnosis

  3. A Validation Study of Adiponectin rs266729 Gene Variant with Type 2 Diabetes, Obesity, and Metabolic Phenotypes in a Taiwanese Population.

    PubMed

    Hsiao, Tun-Jen; Lin, Eugene

    2016-12-01

    Previous data suggesting that a single nucleotide polymorphism (SNP), rs266729, in the adiponectin C1Q and collagen domain containing (ADIPOQ) gene was associated with type 2 diabetes (T2D) have been inconsistent, especially in Asian populations. In this replication study, we aimed to reassess whether the ADIPOQ rs266729 SNP is associated with T2D, obesity, and T2D/obesity-related metabolic traits in a Taiwanese population. A total of 1047 Taiwanese subjects were analyzed. The ADIPOQ rs266729 SNP was genotyped by the Taqman assay. T2D/obesity-related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, creatinine, alanine aminotransferase, and fasting glucose were measured. Our data revealed that the ADIPOQ rs266729 SNP exhibited no association with T2D among the subjects. In addition, no evidence for an association with obesity (BMI ≧27 kg/m(2)) was found for the ADIPOQ rs266729 SNP. Moreover, the ADIPOQ rs266729 SNP did not show any association with T2D/obesity-related metabolic traits among the complete subjects. However, we found an effect modification of obesity on the association between the ADIPOQ rs266729 SNP and total cholesterol (P = 0.00068) only in obese participants after adjusting for age, gender, BMI, and T2D status. Our study indicates that the ADIPOQ rs266729 SNP may influence T2D/obesity-related metabolic traits such as total cholesterol in obese Taiwanese subjects (but not in non-obese subjects).

  4. Pituitary resistin gene expression: effects of age, gender and obesity.

    PubMed

    Morash, Barbara A; Ur, Ehud; Wiesner, Glen; Roy, Jeremy; Wilkinson, Michael

    2004-03-01

    Resistin is a new adipocytokine which is expressed in rat, mouse and possibly human adipose tissue. Its putative role as a mediator of insulin resistance is controversial. We hypothesized that resistin, like leptin, would have multiple roles in non-adipose tissues and we reported that resistin is expressed in mouse brain and pituitary. Moreover, resistin expression in female mouse pituitary is developmentally regulated and maximal expression occurs peripubertally. Although the role of endogenous resistin in mouse brain and pituitary has not been determined, our data suggest that resistin could be important in the postnatal maturation of the hypothalamic-pituitary system. In the present study we compared the ontogeny of resistin gene expression in the pituitary of male and female mice using semi-quantitative RT-PCR analysis. We show that resistin expression is developmentally regulated in the pituitary of male and female CD1 mice. However, significant gender differences were evident (male > female at postnatal day 28 and 42) and this was not modified by neonatal treatment of female pups with testosterone. Since resistin expression in adipose tissue is also influenced by obesity, we evaluated resistin expression in fat, brain and pituitary of the obese ob/ob mouse. Resistin mRNA was significantly increased in both visceral and subcutaneous adipose depots in postnatal day 28 ob/ob mice compared to controls, but pituitary resistin expression was significantly reduced. In contrast to the prepubertal levels, and in agreement with other reports, adipose resistin expression was reduced in adult ob/ob mice. In a third set of experiments we examined the influence of food deprivation on pituitary and fat resistin mRNA. Resistin gene expression was severely down-regulated by a 24-hour fast in adipose and pituitary tissue but not in hypothalamus. In conclusion, pituitary resistin expression is age- and gender-dependent. In ob/ob mice, and in fasted mice, resistin is regulated

  5. 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

  6. Exercise dose and diabetes risk in overweight and obese children: A randomized, controlled trial

    PubMed Central

    Davis, Catherine L; Pollock, Norman K; Waller, Jennifer L; Allison, Jerry D; Dennis, B Adam; Bassali, Reda; Meléndez, Agustín; Boyle, Colleen A; Gower, Barbara A

    2012-01-01

    Context Pediatric studies showed that aerobic exercise reduces metabolic risk, but dose response information is not available. Objective Test the effect of aerobic training dose on insulin resistance, fatness, visceral fat, and fitness in overweight, sedentary children, and test moderation by sex and race. Design, Setting, and Participants Randomized, controlled, efficacy trial from 2003 through 2007, in which 222 overweight or obese, sedentary children (mean age, 9.4 yrs; 42% male, 58% black) were recruited from 15 public schools in the Augusta, GA area. Intervention Low-dose (20 min/d, n = 71) or high-dose (40 min/d, n = 73) aerobic training (13 ± 1.6 wk, 5 d/wk), or control condition (usual physical activity, n = 78); 94% retention. Main outcome measures Prespecified primary outcomes were type 2 diabetes risk at posttest, assessed by insulin area under the curve (AUC) from oral glucose tolerance test, aerobic fitness, percent body fat via dual-energy x-ray absorptiometry, and visceral fat via magnetic resonance, analyzed by intent-to-treat. Results Most children (85%) were obese. At baseline, the mean BMI was 26 (SD = 4.4). Reductions in insulin AUC were larger in the high-dose (adjusted mean difference [95% CI], −3.56 [−6.26 to −0.85], P = .01) than low-dose group (−2.96 [−5.69 to −0.22], P = .03) ×103 μU/mL) vs control group. Dose-response trends were also observed for body fat (−1.4 [−2.2 to −0.7], P < .001; −0.8 [−1.6 to −0.07] %, P =.03) and visceral fat (−3.9 [−6.0 to −1.7], P < .001; −2.8 [−4.9 to −0.6] cm3, P = .01) in the high- and low-dose vs control groups, respectively. Effects in the high- and low-dose groups vs control were similar for fitness (2.4 [0.4 to 4.5], P =.02; 2.4 [0.3 to 4.5] mL/kg/min, P = .03). High- vs. low-dose group effects were similar for these outcomes. There was no moderation by sex or race. Conclusions Three months of 20 or 40 min/d aerobic training improved fitness, and demonstrated dose

  7. Comparison of Age of Onset and Frequency of Diabetic Complications in the Very Elderly Patients with Type 2 Diabetes

    PubMed Central

    2016-01-01

    Background The prevalence of type 2 diabetes in elderly people has increased dramatically in the last few decades. This study was designed to clarify the clinical characteristics of type 2 diabetes in patients aged ≥80 years according to age of onset. Methods We reviewed the medical records of 289 patients aged ≥80 years with type 2 diabetes at the outpatient diabetes clinics of Kangwon National University Hospital from September 2010 to June 2014. We divided the patients into middle-age-onset diabetes (onset before 65 years of age) and elderly-onset diabetes (onset at 65+ years of age). Results There were 141 male and 148 female patients. The patients had a mean age of 83.2±2.9 years and the mean duration of diabetes was 14.3±10.4 years. One hundred and ninety-nine patients had elderly-onset diabetes. The patients with elderly-onset diabetes had a significantly lower frequency of diabetic retinopathy and nephropathy, lower serum creatinine levels, lower glycated hemoglobin (HbA1c) levels, and similar coronary revascularization and cerebral infarction rates compared to those with middle-age-onset diabetes. There was no frequency difference in coronary revascularization and cerebral infarction and HbA1c levels between three subgroups (<5, 5 to 15, and ≥15 years) of diabetes duration in elderly onset diabetes. However, both in the elderly onset diabetes and middle-age-onset diabetes, the cumulative incidence of retinopathy was increasing rapidly according to the duration of diabetes. Conclusion We report that individuals with elderly-onset diabetes have a lower frequency of diabetic retinopathy and nephropathy and similar cardiovascular complications compared to those with middle-age-onset diabetes. PMID:27586451

  8. 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

  9. Carbon dioxide emissions and change in prevalence of obesity and diabetes in the United States: an ecological study.

    PubMed

    Zheutlin, Alexander R; Adar, Sara D; Park, Sung Kyun

    2014-12-01

    Recent studies suggest that increasing levels of the greenhouse gas, carbon dioxide (CO2), may influence weight gain and thus may play a role in rising trends in obesity and diabetes. We conducted an ecological study to examine the associations between CO2 emissions from fossil fuel combustion and changes in the prevalence of obesity and diabetes in the United States. County-level data on CO2 emissions, prevalence of obesity and diagnosed diabetes, other sociodemographic factors and neighborhood characteristics related to urbanicity, and fine particles (PM2.5) between 2004 and 2008 were obtained from the Vulcan Project, Centers for Disease Control and Prevention, and American Community Survey. Linear mixed effect modeling of 3019 counties for the associations between average CO2 emissions and changes in diabetes and obesity prevalence between 2004 and 2008 was performed. The average obesity and diabetes prevalence increased between 2004 and 2008 by 3.65% (SD: 1.88%) and 1.65% (SD: 1.70%), respectively. A marginally significant positive association between CO2 emission and changes in obesity prevalence was found with adjustment for sociodemographic factors, indicators of urbanicity and spatial autocorrelation (p-trend=0.06). The association became weaker and nonsignificant with further adjustment for PM2.5 (p-trend=0.17). There was a significant positive association between CO2 emission and changes in diabetes prevalence before controlling for PM2.5 (p-trend=0.05) but the association became null after controlling for PM2.5 (p-trend=0.49), suggesting that PM2.5 is a critical confounder in the association between CO2 emission and changes in diabetes prevalence. This study does not support the hypothesis that CO2 emissions, a leading driver of climate change, may be linked to increasing trends in obesity and diabetes, though there was an indication of possible link between CO2 and obesity.

  10. Prophylactic fenbendazole therapy does not affect the incidence and onset of type 1 diabetes in non-obese diabetic mice.

    PubMed

    Franke, Deanna D H; Shirwan, Haval

    2006-03-01

    Fenbendazole (FBZ) is a common, highly efficacious broad-spectrum anthelmintic drug used to treat and limit rodent pinworm infections. However, the effect of its prophylactic use on the immune response of rodents is largely undefined. The non-obese diabetic (NOD) mouse is a model commonly used to study type 1 diabetes (T1D). Parasitic infections will inhibit diabetes development in NOD mice; thus, in the presence of contamination, prophylactic treatment with anthelmintics must be considered to maintain experimental research. Herein, we investigated the prophylactic use of FBZ in NOD mice to determine its effect on the incidence and onset of diabetes, lymphocyte sub-populations and T cell proliferative responses. NOD mice were separated into control and treatment groups. The treatment group received a diet containing FBZ. Animals were monitored for the incidence and onset of T1D. At matched time points, diabetic and non-diabetic mice were killed and splenic lymphocytes analyzed for various cell sub-populations and mitogen-induced proliferative responses using flow cytometry. Treated and control mice were monitored >23 weeks with no detectable effects on the incidence or onset of diabetes. Moreover, no significant differences were detected in lymphocyte sub-populations and mitogen-induced CD4(+) and CD8(+) proliferative responses between control and treatment groups. These results suggest that prophylactic FBZ treatment does not significantly alter the incidence or onset of diabetes in NOD mice. The prophylactic use of FBZ, therefore, presents a viable approach for the prevention of pinworm infection in precious experimental animals with substantial scientific and economic benefits.

  11. Distinct genetic control of autoimmune neuropathy and diabetes in the non-obese diabetic background.

    PubMed

    Bour-Jordan, Hélène; Thompson, Heather L; Giampaolo, Jennifer R; Davini, Dan; Rosenthal, Wendy; Bluestone, Jeffrey A

    2013-09-01

    The non-obese diabetic (NOD) mouse is susceptible to the development of autoimmune diabetes but also multiple other autoimmune diseases. Over twenty susceptibility loci linked to diabetes have been identified in NOD mice and progress has been made in the definition of candidate genes at many of these loci (termed Idd for insulin-dependent diabetes). The susceptibility to multiple autoimmune diseases in the NOD background is a unique opportunity to examine susceptibility genes that confer a general propensity for autoimmunity versus susceptibility genes that control individual autoimmune diseases. We previously showed that NOD mice deficient for the costimulatory molecule B7-2 (NOD-B7-2KO mice) were protected from diabetes but spontaneously developed an autoimmune peripheral neuropathy. Here, we took advantage of multiple NOD mouse strains congenic for Idd loci to test the role of these Idd loci the development of neuropathy and determine if B6 alleles at Idd loci that are protective for diabetes will also be for neuropathy. Thus, we generated NOD-B7-2KO strains congenic at Idd loci and examined the development of neuritis and clinical neuropathy. We found that the NOD-H-2(g7) MHC region is necessary for development of neuropathy in NOD-B7-2KO mice. In contrast, other Idd loci that significantly protect from diabetes did not affect neuropathy when considered individually. However, we found potent genetic interactions of some Idd loci that provided almost complete protection from neuritis and clinical neuropathy. In addition, defective immunoregulation by Tregs could supersede protection by some, but not other, Idd loci in a tissue-specific manner in a model where neuropathy and diabetes occurred concomitantly. Thus, our study helps identify Idd loci that control tissue-specific disease or confer general susceptibility to autoimmunity, and brings insight to the Treg-dependence of autoimmune processes influenced by given Idd region in the NOD background.

  12. Short and long sleep are positively associated with obesity, diabetes, hypertension, and cardiovascular disease among adults in the United States.

    PubMed

    Buxton, Orfeu M; Marcelli, Enrico

    2010-09-01

    Research associates short (and to a lesser extent long) sleep duration with obesity, diabetes, and cardiovascular disease; and although 7-8 h of sleep seems to confer the least health risk, these findings are often based on non-representative data. We hypothesize that short sleep (<7 h) and long sleep (>8 h) are positively associated with the risk of obesity, diabetes, hypertension, and cardiovascular disease; and analyze 2004-2005 US National Health Interview Survey data (n=56,507 observations, adults 18-85) to test this. We employ multilevel logistic regression, simultaneously controlling for individual characteristics (e.g., ethnoracial group, gender, age, education), other health behaviors (e.g., exercise, smoking), family environment (e.g., income, size, education) and geographic context (e.g., census region). Our model correctly classified at least 76% of adults on each of the outcomes studied, and sleep duration was frequently more strongly associated with these health risks than other covariates. These findings suggest a 7-8 h sleep duration directly and indirectly reduces chronic disease risk.

  13. Obesity and diabetes as accelerators of functional decline: can lifestyle interventions maintain functional status in high risk older adults?

    PubMed

    Anton, Stephen D; Karabetian, Christy; Naugle, Kelly; Buford, Thomas W

    2013-09-01

    Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and treatment of physical disability in these persons have become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes.

  14. Self–reported diabetes education among Chinese middle–aged and older adults with diabetes

    PubMed Central

    Xu, Hanzhang; Luo, Jianfeng; Wu, Bei

    2016-01-01

    Background To compare self–reported diabetes education among Chinese middle–aged and older adults with diabetes in three population groups: urban residents, migrants in urban settings, and rural residents. Methods We used data from the 2011 China Health and Retirement Longitudinal Study. The sample included 993 participants age 45 and older who reported having diabetes diagnosed from a health professional. We performed multilevel regressions performed to examine the associations between characteristics and different aspects of diabetes education received. Findings Our study shows that 20.24% of the participants received no diabetes education at all. Among those who received information, 46.82% of respondents with diabetes received weight control advice from a health care provider, 90.97% received advice on exercise, 60.37% received diet advice, 35.12% were spoken to smoking control, and only 17.89% of persons were informed of foot care. After controlling socioeconomic factors, life style, number of comorbidities and community factors, we found that compared with migrant population and rural residents, urban residents were more likely to receive diabetes education on diet. Urban residents were also more likely to obtain diabetes education and more aspects of diabetes education comparison with migrants and rural residents. Conclusions Our study suggests diabetes education is a serious concern in China, and a significant proportion of the participants did not receive advice on smoking control and foot care. Rural residents and migrants from rural areas received much less diabetes education compared with urban residents. Efforts to improve diabetes educations are urgently needed in China. PMID:27698998

  15. 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.

  16. Therapeutic Effects of Quercetin on Inflammation, Obesity, and Type 2 Diabetes

    PubMed Central

    Chen, Shuang; Wu, Xiaosong

    2016-01-01

    In previous studies, abdominal obesity has been related to total low-grade inflammation and in some cases has resulted in insulin resistance and other metabolism related disorders such as diabetes. Quercetin is a polyphenol, which is a derivative of plants, and has been shown in vitro as well as in a few animal models to have several potential anti-inflammatory as well as anticarcinogenic applications. The substance has also been shown to aid in the attenuation of lipid peroxidation, platelet aggregation, and capillary permeability. However, further research is called for to gain a better understanding of how quercetin is able to provide these beneficial effects. This manuscript reviewed quercetin's anti-inflammatory properties in relation to obesity and type 2 diabetes. PMID:28003714

  17. 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.

  18. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes.

    PubMed

    Musso, Giovanni; Gambino, Roberto; Cassader, Maurizio

    2011-01-01

    Novel, culture-independent, molecular and metagenomic techniques have provided new insight into the complex interactions between the mammalian host and gut microbial species. It is increasingly evident that gut microbes may shape the host metabolic and immune network activity and ultimately influence the development of obesity and diabetes. We discuss the evidence connecting gut microflora to obesity and to type 1 and type 2 diabetes, and we present recent insights into potential mechanisms underlying this relationship: increased nutrient absorption from the diet, prolonged intestinal transit time, altered bile acid entero-hepatic cycle, increased cellular uptake of circulating triglycerides, enhanced de novo lipogenesis, reduced free fatty acid oxidation, altered tissue composition of biologically active polyunsaturated fatty acid, chronic low-grade inflammation triggered by the endotoxin toll-like receptor 4 axis, and altered intestinal barrier function.

  19. 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.

  20. Prevalence of diabetes mellitus and obesity in the Keewatin District of the Canadian Arctic.

    PubMed

    Orr, P H; Martin, B D; Patterson, K; Moffatt, M E

    1998-01-01

    Through a medical chart review, the prevalence of diagnosed diabetes mellitus in Inuit of the Keewatin District of the Canadian Northwest Territories was determined to be 0.27%. All cases were in adults, and no cases of gestational diabetes were noted. The prevalence and pattern of obesity were determined from measurements of body mass index (BMI), skinfold thickness, and waist-hip ratio obtained during the 1990-91 Keewatin Health Assessment Study. Thirty-one percent of 414 randomly identified adults (29% of men, 37% of women) were overweight (BMI > 27). Central fat patterning was more prevalent in women and less prevalent in men from the Keewatin compared to the general Canadian population. Comparison of skinfold thickness values to published measurements obtained from earlier arctic surveys supports the hypothesis that changes in diet and activity levels associated with urbanization have resulted in increased obesity in the Inuit.

  1. Calcium homeostasis and organelle function in the pathogenesis of obesity and diabetes

    PubMed Central

    Arruda, Ana Paula; Hotamisligil, Gökhan S.

    2015-01-01

    Summary A number of chronic metabolic pathologies, including obesity, diabetes, cardiovascular disease, asthma, and cancer cluster together to present the greatest threat to human health. As research in this field has advanced, it has become clear that unresolved metabolic inflammation, organelle dysfunction, and other cellular and metabolic stresses underlie the development of these chronic metabolic diseases. However, the relationship between these systems and pathological mechanisms is poorly understood. Here, we will discuss the role of cellular Ca2+ homeostasis as a critical mechanism integrating the myriad of cellular and subcellular dysfunctional networks found in metabolic tissues such as liver and adipose tissue in the context of metabolic disease particularly in obesity and diabetes. PMID:26190652

  2. Advances in the Science, Treatment, and Prevention of the Disease of Obesity: Reflections From a Diabetes Care Editors’ Expert Forum

    PubMed Central

    Bray, George A.; Home, Philip D.; Garvey, W. Timothy; Klein, Samuel; Pi-Sunyer, F. Xavier; Hu, Frank B.; Raz, Itamar; Van Gaal, Luc; Wolfe, Bruce M.; Ryan, Donna H.

    2015-01-01

    As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave concern. In June 2014, a Diabetes Care Editors’ Expert Forum convened to review the state of obesity research and discuss the latest prevention initiatives and behavioral, medical, and surgical therapies. This article, an outgrowth of the forum, offers an expansive view of the obesity epidemic, beginning with a discussion of its root causes. Recent insights into the genetic and physiological factors that influence body weight are reviewed, as are the pathophysiology of obesity-related metabolic dysfunction and the concept of metabolically healthy obesity. The authors address the crucial question of how much weight loss is necessary to yield meaningful benefits. They describe the challenges of behavioral modification and predictors of its success. The effects of diabetes pharmacotherapies on body weight are reviewed, including potential weight-neutral combination therapies. The authors also summarize the evidence for safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The article concludes with an impassioned call for researchers, clinicians, governmental agencies, health policymakers, and health-related industries to collectively embrace the urgent mandate to improve prevention and treatment and for society at large to acknowledge and manage obesity as a serious disease. PMID:26421334

  3. 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.

  4. 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

  5. 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

  6. Ubc13 haploinsufficiency protects against age-related insulin resistance and high-fat diet-induced obesity

    PubMed Central

    Joo, Erina; Fukushima, Toru; Harada, Norio; Reed, John C.; Matsuzawa, Shu-ichi; Inagaki, Nobuya

    2016-01-01

    Obesity is associated with low-grade inflammation that leads to insulin resistance and type 2 diabetes via Toll-like Receptor (TLR) and TNF-family cytokine receptor (TNFR) signaling pathways. Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical K63-linked polyubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in TLR and TNFR pathways. However, the relationship between Ubc13 and metabolic disease remains unclear. In this study, we investigated the role of Ubc13 in insulin resistance and high-fat diet (HFD)-induced obesity. We compared wild-type (WT) and Ubc13 haploinsufficient (ubc13+/−) mice under normal diet (ND) and HFD, since homozygous knockout mice (ubc13−/−) are embryonic lethal. Male and female ubc13+/− mice were protected against age-related insulin resistance under ND and HFD compared to WT mice. Interestingly, only female ubc13+/− mice were protected against HFD-induced obesity and hepatic steatosis. Moreover, only female HFD-fed ubc13+/− mice showed lower expression of inflammatory cytokines that was secondary to reduction in weight gain not present in the other groups. In summary, our results indicate that suppression of Ubc13 activity may play a metabolic role independent of its inflammatory function. Thus, Ubc13 could represent a therapeutic target for insulin resistance, diet-induced obesity, and associated metabolic dysfunctions. PMID:27796312

  7. Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

    PubMed Central

    El husseny, Mostafa Wanees Ahmed; Mamdouh, Mediana; Shaban, Sara; Zaki, Marwa Mostafa Mohamed; Ahmed, Osama M.

    2017-01-01

    Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP) and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM), insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity. PMID:28286779

  8. Mitochondrial alteration in type 2 diabetes and obesity: an epigenetic link.

    PubMed

    Cheng, Zhiyong; Almeida, Fabio A

    2014-01-01

    The growing epidemic of type 2 diabetes mellitus (T2DM) and obesity is largely attributed to the current lifestyle of over-consumption and physical inactivity. As the primary platform controlling metabolic and energy homeostasis, mitochondria show aberrant changes in T2DM and obese subjects. While the underlying mechanism is under extensive investigation, epigenetic regulation is now emerging to play an important role in mitochondrial biogenesis, function, and dynamics. In line with lifestyle modifications preventing mitochondrial alterations and metabolic disorders, exercise has been shown to change DNA methylation of the promoter of PGC1α to favor gene expression responsible for mitochondrial biogenesis and function. In this article we discuss the epigenetic mechanism of mitochondrial alteration in T2DM and obesity, and the effects of lifestyle on epigenetic regulation. Future studies designed to further explore and integrate the epigenetic mechanisms with lifestyle modification may lead to interdisciplinary interventions and novel preventive options for mitochondrial alteration and metabolic disorders.

  9. Peroxisome proliferator-activated receptor: effects on nutritional homeostasis, obesity and diabetes mellitus.

    PubMed

    Viana Abranches, M; Esteves de Oliveira, F C; Bressan, J

    2011-01-01

    The obesity and the metabolic disorders associated characterize the metabolic syndrome, which has increased at an alarming rate around the world. It is known that environmental and genetic factors are involved in the genesis of obesity. Peroxisome Proliferator-Activated Receptors (PPARs) stand out among these factors. They compose the nuclear receptor superfamily and there are in three isoforms (PPARα,PPARβ/δ and PPARγ), which play an important role in the regulation of the metabolism of carbohydrates, lipids and proteins. The present review aims to understand the relationship between the diet, the PPARs and the control of the blood glucose and body weight, since the understanding about the mechanisms by which these receptors act may benefit the development of the strategies aiming at prevention and elaboration of therapeutics actions which are more effective for the treatment of obesity and diabetes.

  10. Physical activity in children: prevention of obesity and type 2 diabetes.

    PubMed

    Rush, Elaine; Simmons, David

    2014-01-01

    There is strong evidence that increased physical activity is beneficial for blood glucose homeostasis and the prevention of obesity and type 2 diabetes mellitus. This chapter takes a life course approach with an emphasis on the intrauterine and childhood stages of life. Firstly, growth and development at critical periods with a focus on skeletal muscle and adipose tissue; then, obesity and type 2 diabetes mellitus are considered in relation to physical activity and sedentary behaviour. The importance of the development of fundamental movement skills in early childhood for both physical fitness and also growth and development is emphasised. Physical activity guidelines in westernised countries are examined for commonalities. Finally, the effective translation of the evidence base for the benefits of physical activity into randomised controlled trials and then into real-world public health services that are sustainable is addressed with a case study from New Zealand of Project Energize--a through-school physical activity and nutrition intervention. Physical activity, alongside a 'healthy diet' is arguably the best preventive measure and treatment for both obesity and type 2 diabetes. It is an essential and normal activity of daily life, and all aspects of the life course and the environment should support physical activity.

  11. Mediterranean diet rich in olive oil and obesity, metabolic syndrome and diabetes mellitus.

    PubMed

    Pérez-Martínez, Pablo; García-Ríos, Antonio; Delgado-Lista, Javier; Pérez-Jiménez, Francisco; López-Miranda, José

    2011-01-01

    After decades of epidemiological, clinical and experimental research, it has become clear that consumption of Mediterranean dietary patterns rich in olive oil has a profound influence on health outcomes, including obesity, metabolic syndrome (MetS) and diabetes mellitus. Traditionally, many beneficial properties associated with this oil have been ascribed to its high oleic acid content. Olive oil, however, is a functional food that, besides having high-monounsaturated (MUFA) content, contains other minor components with biological properties. In this line, phenolic compounds have shown antioxidant and antiinflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Research into the pharmacological properties of the minor components of olive oil is very active and could lead to the formulation of functional food and nutraceuticals. Although more data are mandatory the Mediterranean diet rich in olive oil does not contribute to obesity and appears to be a useful tool in the lifestyle management of the MetS. Moreover there is good scientific support for MUFA diets, especially those based on olive oil, as an alternative approach to low-fat diets for the medical nutritional therapy in diabetes. The objective of this review is to present evidence illustrating the relationship between Mediterranean diet, olive oil and metabolic diseases, including obesity, MetS and diabetes mellitus and to discuss potential mechanisms by which this food can help in disease prevention and treatment.

  12. Obesity and Diabetes in Vulnerable Populations: Reflection on Proximal and Distal Causes

    PubMed Central

    Candib, Lucy M.

    2007-01-01

    Around the world obesity and diabetes are climbing to epidemic proportion, even in countries previously characterized by scarcity. Likewise, people from low-income and minority communities, as well as immigrants from the developing world, increasingly visit physicians in North America with obesity, metabolic syndrome, or diabetes. Explanations limited to lifestyle factors such as diet and exercise are inadequate to explain the universality of what can be called a syndemic, a complex and widespread phenomenon in population health produced by multiple reinforcing conditions. Underlying the problem are complex factors—genetic, physiological, psychological, familial, social, economic, and political—coalescing to overdetermine these conditions. These interacting factors include events occurring during fetal life, maternal physiology and life context, the thrifty genotype, the nutritional transition, health impact of urbanization and immigration, social attributions and cultural perceptions of increased weight, and changes in food costs and availability resulting from globalization. Better appreciation of the complexity of causation underlying the worldwide epidemic of obesity and diabetes can refocus the work of clinicians and researchers to work at multiple levels to address prevention and treatment for these conditions among vulnerable populations. PMID:18025493

  13. Nutrigenomic basis of beneficial effects of chromium(III) on obesity and diabetes.

    PubMed

    Lau, Francis C; Bagchi, Manashi; Sen, Chandan K; Bagchi, Debasis

    2008-10-01

    Insulin resistance has been shown to be the major contributing factor to the metabolic syndrome, which comprises a cluster of risk factors for metabolic aberrations such as obesity, dyslipidemia, hypertension, and hyperglycemia. Additionally, insulin resistance has been associated with the occurrence of cardiovascular disease and type 2 diabetes. Epidemiological studies indicate that obesity and diabetes have become alarmingly prevalent in recent years. Substantial evidence suggests that dietary interventions and regular exercise greatly improve body mass index and lipid profile as well as alleviate insulin resistance. Therefore, dietary supplements such as insulin-sensitizing agents may be beneficial in the prevention and treatment of obesity and type 2 diabetes. Numerous in vitro and in vivo studies suggest that chromium supplements, particularly niacin-bound chromium or chromium-nicotinate, may be effective in attenuating insulin resistance and lowering plasma cholesterol levels. Utilizing the powerful technology of nutrigenomics to identify the genes regulated by chromium supplementation may shed some light on the underlying mechanisms of chromium-gene interactions, and thus provide strategies to mitigate and prevent insulin-resistance-related disorders.

  14. 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.

  15. Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice

    PubMed Central

    Fukuta, Kazufumi; Shirakami, Yohei; Maruta, Akinori; Obara, Koki; Iritani, Soichi; Nakamura, Nobuhiko; Kochi, Takahiro; Kubota, Masaya; Sakai, Hiroyasu; Tanaka, Takuji; Shimizu, Masahito

    2017-01-01

    Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks. At the time of sacrifice, PTX administration markedly suppressed the development of premalignant lesions in the colorectum. The levels of oxidative stress markers were significantly decreased in the PTX-treated group compared with those in the untreated control group. In PTX-administered mice, the mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and TNF-α, and the number of proliferating cell nuclear antigen (PCNA)-positive cells in the colonic mucosa, were significantly reduced. These observations suggest that PTX attenuated chronic inflammation and oxidative stress, and prevented the development of colonic tumorigenesis in an obesity-related colon cancer model. PMID:28212276

  16. Carbonylated plasma proteins as potential biomarkers of obesity induced type 2 diabetes mellitus.

    PubMed

    Bollineni, Ravi Chand; Fedorova, Maria; Blüher, Matthias; Hoffmann, Ralf

    2014-11-07

    Protein carbonylation is a common nonenzymatic oxidative post-translational modification, which is often considered as biomarker of oxidative stress. Recent evidence links protein carbonylation also to obesity and type 2 diabetes mellitus (T2DM), though the protein targets of carbonylation in human plasma have not been identified. In this study, we profiled carbonylated proteins in plasma samples obtained from lean individuals and obese patients with or without T2DM. The plasma samples were digested with trypsin, carbonyl groups were derivatized with O-(biotinylcarbazoylmethyl)hydroxylamine, enriched by avidin affinity chromatography, and analyzed by RPC-MS/MS. Signals of potentially modified peptides were targeted in a second LC-MS/MS analysis to retrieve the peptide sequence and the modified residues. A total of 158 unique carbonylated proteins were identified, of which 52 were detected in plasma samples of all three groups. Interestingly, 36 carbonylated proteins were detected only in obese patients with T2DM, whereas 18 were detected in both nondiabetic groups. The carbonylated proteins originated mostly from liver, plasma, platelet, and endothelium. Functionally, they were mainly involved in cell adhesion, signaling, angiogenesis, and cytoskeletal remodeling. Among the identified carbonylated proteins were several candidates, such as VEGFR-2, MMP-1, argin, MKK4, and compliment C5, already connected before to diabetes, obesity and metabolic diseases.

  17. Omentin-1 plasma levels and cholesterol metabolism in obese patients with diabetes mellitus type 1: impact of weight reduction

    PubMed Central

    Lesná, J; Tichá, A; Hyšpler, R; Musil, F; Bláha, V; Sobotka, L; Zadák, Z; Šmahelová, A

    2015-01-01

    Background: Omentin-1 is an anti-inflammatory adipokine produced preferentially by visceral adipose tissue. Plasma levels of omentin-1 are decreased in obesity and other insulin-resistant states. Insulin resistance contributes to the changes of cholesterol synthesis and absorption as well. The aim of this study was to characterise omentin-1 plasma levels in obese patients with diabetes mellitus type 1 during weight reduction, and to elucidate the relationship between cholesterol metabolism and omentin-1. Methods: Plasma levels of omentin-1 were measured in obese type 1 diabetics (n=14, body mass index >30 kg m−2, age 29–62 years) by enzyme-linked immunosorbent assay (BioVendor). Gas chromatography with flame ionisation detector (Fisons Plc.,) was used to measure squalene and non-cholesterol sterols—markers of cholesterol synthesis and absorption (phase I). Measurements were repeated after 1 month (phase II; 1 week of fasting in the hospital setting and 3 weeks on a diet containing 150 g saccharides per day) and after 1 year (phase III) on a diet with 225 g saccharides per day. Results: Omentin-1 plasma levels were stable during phases I and II, but significantly increased (P<0.001) during phase III. Omentin-1 plasma dynamics were significantly associated with plasma levels of high-density lipoprotein (P=0.005) and triacylglycerols (P=0.01), as well as with lathosterol (P=0.03). Conclusion: Omentin-1 plasma levels significantly increased during the weight reduction programme. Omentin-1 plasma dynamics suggest a close relationship with cholesterol metabolism. PMID:26524638

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

    PubMed Central

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

    2012-01-01

    OBJECTIVE 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. MATERIALS/METHODS 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. RESULTS 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. CONCLUSIONS 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. Impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women.

    PubMed

    Surekha, T; Himabindu, Y; Sriharibabu, M; Pandey, Anil Kumar

    2014-01-01

    Physical inactivity is a leading risk factor for overweight and obesity in the society. Prevalence of overweight and obesity in the reproductive age group women not only affects maternal health but also the health of the off spring. Infertility is a common problem in India affecting 13-19 million people at any given time. Even though it is not life threatening, infertility causes intense mental agony and trauma that can only be best described by infertile couples themselves. Infertility is more common in overweight and obese individuals compared to normal weight individuals. Decreasing ovarian reserve is an important factor for infertility in women. This study examined the impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women. The observations made in this study reveal that physical activity improves ovarian reserve markers in all reproductive age women but this improvement is more distinct and statistically significant in overweight and obese women compared to normal weight women.

  20. 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.

  1. 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…

  2. Using weight-for-age percentiles to screen for overweight and obese children and adolescents.

    PubMed

    Gamliel, Adir; Ziv-Baran, Tomer; Siegel, Robert M; Fogelman, Yacov; Dubnov-Raz, Gal

    2015-12-01

    There are relatively low rates of screening for overweight and obesity among children and adolescents in primary care. A simplified method for such screening is needed. The study objective was to examine if weight-for-age percentiles are sufficiently sensitive in identifying overweight and obesity in children and adolescents. We used data from two distinct sources: four consecutive cycles of the National Health and Nutrition Examination Surveys (NHANES) from the years 2005 to 2012, using participants aged 2-17.9 years for whom data on age, sex, weight, and height were available (n=12,884), and primary care clinic measurements (n=15,152). Primary outcomes were the threshold values of weight-for-age percentiles which best discriminated between normal weight, overweight, and obesity status. Receiver operating characteristic analyses demonstrated that weight-for-age percentiles well discriminated between normal weight and overweight and between non-obese and obese individuals (area under curve=0.956 and 0.977, respectively, both p<0.001). Following Classification and Regression Trees analysis, the 90th and 75th weight-for-age percentiles were chosen as appropriate cutoffs for obesity and overweight, respectively. These cutoffs had high sensitivity and negative predictive value in identifying obese participants (94.3% and 98.6%, respectively, for the 90th percentile) and in identifying overweight participants (93.2% and 95.9%, respectively, for the 75th percentile). The sensitivities and specificities were nearly identical across race and sex, and in the validation data from NHANES 2011 to 2012 and primary care. We conclude that weight-for-age percentiles can discriminate between normal weight, overweight and obese children, and adolescents. The 75th and 90th weight-for-age percentiles correspond well with the BMI cutoffs for pediatric overweight and obesity, respectively.

  3. Obesity and metabolic surgery in type 1 diabetes mellitus.

    PubMed

    Raab, Heike; Weiner, R A; Frenken, M; Rett, K; Weiner, S

    2013-03-01

    Introducción: La cirugía de la obesidad es un método eficaz para el tratamiento de la obesidad y la diabetes mellitus tipo 2. Este tipo de diabetes puede se resuelve por completo en el 78,1% de los pacientes diabéticos y mejora en el 86,6% de los pacientes diabéticos. Sin embargo, poco se sabe acerca de la cirugía bariátrica en la diabetes mellitus tipo 1. Métodos: Presentamos 6 pacientes mujeres obesas con diabetes mellitus tipo 1 que se sometieron a cirugía bariátrica. Dos de ellas fueron sometidas a un bypass gástrico en-Y-Roux (BPGYR), una se le realizó una gastrectomía en manga y a las tres restantes una derivación biliopancreática con-switch duodenal (DBP-SD). Resultados: Nuestros resultados mostraron una reducción de peso notable, así como una mejora en el control de la glucosa en sangre y el requerimiento de insulina en los años de seguimiento después de la cirugía. El IMC prequirúrgico de las 6 pacientes osciló entre 37,3-46,0 kg/m2 y mejoró a 25,8-29,0 kg/m2 un año después de la cirugía. La HbA1c disminuyó de 6,7-9,8% antes de la cirugía a 5,7-8,5% un año después de la cirugía. El requerimiento diario de insulina se redujo de 62-150 UI/día antes de la cirugía a 15-54 UI /día al cabo de un año. Conclusión: Los resultados son impresionantes y muestran una mejora en la sensibilidad a la insulina tras una cirugía de la obesidad. No obstante, un control óptimo de la glucosa de sangre sigue siendo muy importante en la terapia de la diabetes mellitus tipo 1 para evitarcomplicaciones a largo plazo.

  4. Association of hepatitis C with insulin resistance and type 2 diabetes in US general population: the impact of the epidemic of obesity.

    PubMed

    Stepanova, M; Lam, B; Younossi, Y; Srishord, M K; Younossi, Z M

    2012-05-01

    Studies from tertiary care medical centres have linked hepatitis C virus (HCV) to the development of insulin resistance (IR) and type 2 diabetes. The aim of the study is to assess the relationship between HCV positivity and insulin resistance/diabetes in the US population. Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 1988 and 2008 were used. HCV infection was diagnosed using a positive serologic anti-HCV test. Additionally, diabetes was diagnosed as fasting blood glucose ≥126 mg/dL and/or the use of hypoglycaemic medications. Insulin resistance was defined as a homeostasis of model assessment (HOMA) score of >3.0. Logistic regression was used to estimate the odds ratios (ORs) of each of the potential risk factors for diabetes mellitus (DM). The SUDAAN 10.0 was used to run descriptive and regression analyses. A total of 39 506 individuals from three NHANES cycles (1988-1994, 1999-2004 and 2005-2008) with complete demographic and relevant clinical data were included. Over these three NHANES cycles, prevalence of hepatitis C did not significantly change. During the first NHANES cycle (1988-1994), insulin and diabetes were independently associated with hepatitis C. However, during the later study cycles (1998-2008), these associations were no longer significant. In contrast, other important known risk factors for diabetes and IR (male gender, non-Caucasian race, age and obesity) remained significant over all three NHANES cycles. Although HCV infection was independently associated with an increased risk of diabetes and IR in the US population over a decade ago, assessment of the later NHANES cycles shows that this relationship may have become diluted by the rapid rise of other risks for diabetes, specifically, the prevalence of obesity.

  5. Adipose tissue macrophages in the Development of Obesity-induced Inflammation, Insulin Resistance and Type 2 Diabetes

    PubMed Central

    Lee, Jongsoon

    2014-01-01

    It has been increasingly accepted that chronic subacute inflammation plays an important role in the development of insulin resistance and Type 2 Diabetes in animals and humans. Particularly supporting this is that suppression of systemic inflammation in Type 2 Diabetes improves glycemic control; this also points to a new potential therapeutic target for the treatment of Type 2 Diabetes. Recent studies strongly suggest that obesity-induced inflammation is mainly mediated by tissue resident immune cells, with particular attention being focused on adipose tissue macrophages (ATMs). This review delineates the current progress made in understanding obesity-induced inflammation and the roles ATMs play in this process. PMID:23397293

  6. Associations between sleep loss and increased risk of obesity and diabetes.

    PubMed

    Knutson, Kristen L; Van Cauter, Eve

    2008-01-01

    During the past few decades, sleep curtailment has become a very common 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. Evidence is rapidly accumulating 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 waking 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.

  7. 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

  8. 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.

  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. 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

  11. 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

  12. Robotic pancreas transplantation in a type 1 diabetic patient with morbid obesity

    PubMed Central

    Yeh, Chun Chieh; Spaggiari, Mario; Tzvetanov, Ivo; Oberholzer, José

    2017-01-01

    Abstract Rationale: Obesity is considered a relative contraindication to pancreas transplantation due to increased risks of wound-related complications. Robotic surgeries have never been applied for pancreas transplantation in obese recipients though robotic kidney transplantation did and already proved its value in reducing wound-related complications in obese recipients. Patient concerns & Diagnoses: We performed the first robotic pancreas after kidney transplantation for a 34-year-old Hispanic type 1 diabetic male with class III obesity (BMI = 41 kg/m2). Interventions: The pancreas graft was procured and benched in the standard fashion. Methylene blue was used to detect any vascular leaks. The operation was completed via two 12-mm ports (camera, laparoscopic bed-side assistance), two 8-mm ports for robotic arms, and a 7-cm epigastric incision for hand port. The portal vein and arterial Y-graft of the pancreas were anastomosed to the recipient's left external iliac vein and artery, respectively. Duodenum-bladder drainage was performed with a circular stapler. Outcomes: Duration of warm and cold ischemia was: 45 minutes and 7 hours, respectively. The patient was discharged uneventfully without wound-related complications. Excellent metabolic control was achieved with hemoglobin A1c lowering from 9% before transplantation to 4.4% on day 120. The patient remained in nondiabetic status in 1-year follow-up. Lessons: In conclusion, robotic pancreas transplantation is feasible in patients with morbid obesity. PMID:28178127

  13. The update of anthocyanins on obesity and type 2 diabetes: experimental evidence and clinical perspectives.

    PubMed

    Guo, Honghui; Ling, Wenhua

    2015-03-01

    With the dramatically increasing prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide, there is an urgent need for new strategies to combat the growing epidemic of these metabolic diseases. Diet is an essential factor affecting the development of and risk for obesity and T2DM and it can either help or hurt. In searching for preventative and therapeutic strategies, it is therefore advantageous to consider the potential of certain foods and their bioactive compounds to reverse or prevent the pathogenic processes associated with metabolic disease. Anthocyanins are naturally occurring polyphenolic compounds abundant in dark-colored fruits, vegetables and grains. Epidemiological studies suggest that increased consumption of anthocyanins lowers the risk of T2DM. Many in vitro and in vivo studies also reveal an array of mechanisms through which anthocyanins could prevent or reverse obesity- and T2DM-related pathologies including promotion of antioxidant and anti-inflammatory activities, improvement of insulin resistance, and hypolipidemic and hypoglycemic actions. Here, we summarize the data on anthocyanin-mediated protection against obesity and T2DM and the underlying mechanisms. Further population-based and long-term human intervention studies are necessary to ultimately evaluate the use of anthocyanins for protection/prevention against the development of obesity and T2DM.

  14. 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

  15. 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.

  16. 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

    2014-06-20

    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.

  17. 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.

  18. Novel canine models of obese prediabetes and mild type 2 diabetes

    PubMed Central

    Liu, Huiwen; Mooradian, Vahe; Castro, Ana Valeria B.; Kabir, Morvarid; Stefanovski, Darko; Zheng, Dan; Kirkman, Erlinda L.; Bergman, Richard N.

    2010-01-01

    Human type 2 diabetes mellitus (T2DM) is often characterized by obesity-associated insulin resistance (IR) and β-cell function deficiency. Development of relevant large animal models to study T2DM is important and timely, because most existing models have dramatic reductions in pancreatic function and no associated obesity and IR, features that resemble more T1DM than T2DM. Our goal was to create a canine model of T2DM in which obesity-associated IR occurs first, followed by moderate reduction in β-cell function, leading to mild diabetes or impaired glucose tolerance. Lean dogs (n = 12) received a high-fat diet that increased visceral (52%, P < 0.001) and subcutaneous (130%, P < 0.001) fat and resulted in a 31% reduction in insulin sensitivity (SI) (5.8 ± 0.7 × 10−4 to 4.1 ± 0.5 × 10−4 μU·ml−1·min−1, P < 0.05). Animals then received a single low dose of streptozotocin (STZ; range 30–15 mg/kg). The decrease in β-cell function was dose dependent and resulted in three diabetes models: 1) frank hyperglycemia (high STZ dose); 2) mild T2DM with normal or impaired fasting glucose (FG), 2-h glucose >200 mg/dl during OGTT and 77–93% AIRg reduction (intermediate dose); and 3) prediabetes with normal FG, normal 2-h glucose during OGTT and 17–74% AIRg reduction (low dose). Twelve weeks after STZ, animals without frank diabetes had 58% more body fat, decreased β-cell function (17–93%), and 40% lower SI. We conclude that high-fat feeding and variable-dose STZ in dog result in stable models of obesity, insulin resistance, and 1) overt diabetes, 2) mild T2DM, or 3) impaired glucose tolerance. These models open new avenues for studying the mechanism of compensatory changes that occur in T2DM and for evaluating new therapeutic strategies to prevent progression or to treat overt diabetes. PMID:19843874

  19. Genetic Evidence for a Causal Role of Obesity in Diabetic Kidney Disease.

    PubMed

    Todd, Jennifer N; Dahlström, Emma H; Salem, Rany M; Sandholm, Niina; Forsblom, Carol; McKnight, Amy J; Maxwell, Alexander P; Brennan, Eoin; Sadlier, Denise; Godson, Catherine; Groop, Per-Henrik; Hirschhorn, Joel N; Florez, Jose C

    2015-12-01

    Obesity has been posited as an independent risk factor for diabetic kidney disease (DKD), but establishing causality from observational data is problematic. We aimed to test whether obesity is causally related to DKD using Mendelian randomization, which exploits the random assortment of genes during meiosis. In 6,049 subjects with type 1 diabetes, we used a weighted genetic risk score (GRS) comprised of 32 validated BMI loci as an instrument to test the relationship of BMI with macroalbuminuria, end-stage renal disease (ESRD), or DKD defined as presence of macroalbuminuria or ESRD. We compared these results with cross-sectional and longitudinal observational associations. Longitudinal analysis demonstrated a U-shaped relationship of BMI with development of macroalbuminuria, ESRD, or DKD over time. Cross-sectional observational analysis showed no association with overall DKD, higher odds of macroalbuminuria (for every 1 kg/m(2) higher BMI, odds ratio [OR] 1.05, 95% CI 1.03-1.07, P < 0.001), and lower odds of ESRD (OR 0.95, 95% CI 0.93-0.97, P < 0.001). Mendelian randomization analysis showed a 1 kg/m(2) higher BMI conferring an increased risk in macroalbuminuria (OR 1.28, 95% CI 1.11-1.45, P = 0.001), ESRD (OR 1.43, 95% CI 1.20-1.72, P < 0.001), and DKD (OR 1.33, 95% CI 1.17-1.51, P < 0.001). Our results provide genetic evidence for a causal link between obesity and DKD in type 1 diabetes. As obesity prevalence rises, this finding predicts an increase in DKD prevalence unless intervention should occur.

  20. Genetic Evidence for a Causal Role of Obesity in Diabetic Kidney Disease

    PubMed Central

    Todd, Jennifer N.; Dahlström, Emma H.; Salem, Rany M.; Sandholm, Niina; Forsblom, Carol; McKnight, Amy J.; Maxwell, Alexander P.; Brennan, Eoin; Sadlier, Denise; Godson, Catherine; Groop, Per-Henrik; Hirschhorn, Joel N.

    2015-01-01

    Obesity has been posited as an independent risk factor for diabetic kidney disease (DKD), but establishing causality from observational data is problematic. We aimed to test whether obesity is causally related to DKD using Mendelian randomization, which exploits the random assortment of genes during meiosis. In 6,049 subjects with type 1 diabetes, we used a weighted genetic risk score (GRS) comprised of 32 validated BMI loci as an instrument to test the relationship of BMI with macroalbuminuria, end-stage renal disease (ESRD), or DKD defined as presence of macroalbuminuria or ESRD. We compared these results with cross-sectional and longitudinal observational associations. Longitudinal analysis demonstrated a U-shaped relationship of BMI with development of macroalbuminuria, ESRD, or DKD over time. Cross-sectional observational analysis showed no association with overall DKD, higher odds of macroalbuminuria (for every 1 kg/m2 higher BMI, odds ratio [OR] 1.05, 95% CI 1.03–1.07, P < 0.001), and lower odds of ESRD (OR 0.95, 95% CI 0.93–0.97, P < 0.001). Mendelian randomization analysis showed a 1 kg/m2 higher BMI conferring an increased risk in macroalbuminuria (OR 1.28, 95% CI 1.11–1.45, P = 0.001), ESRD (OR 1.43, 95% CI 1.20–1.72, P < 0.001), and DKD (OR 1.33, 95% CI 1.17–1.51, P < 0.001). Our results provide genetic evidence for a causal link between obesity and DKD in type 1 diabetes. As obesity prevalence rises, this finding predicts an increase in DKD prevalence unless intervention should occur. PMID:26307587

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Role of Environmental Chemicals in Diabetes and Obesity: A National Toxicology Program Workshop Review

    PubMed Central

    Heindel, Jerrold J.; Bucher, John R.; Gallo, Michael A.

    2012-01-01

    Background: There has been increasing interest in the concept that exposures to environmental chemicals may be contributing factors to the epidemics of diabetes and obesity. On 11–13 January 2011, the National Institute of Environmental Health Sciences (NIEHS) Division of the National Toxicology Program (NTP) organized a workshop to evaluate the current state of the science on these topics of increasing public health concern. Objective: The main objective of the workshop was to develop recommendations for a research agenda after completing a critical analysis of the literature for humans and experimental animals exposed to certain environmental chemicals. The environmental exposures considered at the workshop were arsenic, persistent organic pollutants, maternal smoking/nicotine, organotins, phthalates, bisphenol A, and pesticides. High-throughput screening data from Toxicology in the 21st Century (Tox21) were also considered as a way to evaluate potential cellular pathways and generate -hypotheses for testing which and how certain chemicals might perturb biological processes related to diabetes and obesity. Conclusions: Overall, the review of the existing literature identified linkages between several of the environmental exposures and type 2 diabetes. There was also support for the “developmental obesogen” hypothesis, which suggests that chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes or the development of neural circuits that regulate feeding behavior. The effects may be most apparent when the developmental exposure is combined with consumption of a high-calorie, high-carbohydrate, or high-fat diet later in life. Research on environmental chemical exposures and type 1 diabetes was very limited. This lack of research was considered a critical data gap. In this workshop review, we outline the major themes that emerged from the workshop and discuss activities that NIEHS/NTP is undertaking to address research

  6. Relevance of sodium/glucose cotransporter-1 (SGLT1) to diabetes mellitus and obesity in dogs.

    PubMed

    Batchelor, D J; German, A J; Shirazi-Beechey, S P

    2013-04-01

    Glucose transport across the enterocyte brush border membrane by sodium/glucose cotransporter-1 (SGLT1, coded by Slc5a1) is the rate-limiting step for intestinal glucose transport. The relevance of SGLT1 expression in predisposition to diabetes mellitus and to obesity was investigated in dogs. Cultured Caco-2/TC7 cells were shown to express SGLT1 in vitro. A 2-kbp fragment of the Slc5a1 5' flanking region was cloned from canine genomic DNA, ligated into reporter gene plasmids, and shown to drive reporter gene expression in these cells above control (P < 0.001). To determine the effect of the 3 known SNPs in this region on promoter function, new promoter/reporter constructs (all permutations of these 3 SNPs) were created by site-directed mutagenesis. No significant differences in promoter function were seen, suggesting that these SNPs do not have a significant effect on the constitutive transcription of SGLT1 mRNA in dogs. A search for novel SNPs in this region in dogs was made in 2 breeds predisposed to diabetes mellitus (Samoyed and cairn terrier), 2 breeds that rarely develop diabetes (boxer and German shepherd), and 2 breeds predisposed to obesity (Labrador retriever and cocker spaniel). The Slc5a1 5' flanking region was amplified from 10 healthy individuals of each of these breeds by high-fidelity PCR with the use of breed-labeled primers and sequenced by pyrosequencing. The sequence of the Slc5a1 5' flanking region in all individuals of all breeds tested was identical. On this evidence, variations in Slc5a1 promoter sequence between dogs do not influence the pathogenesis of diabetes mellitus or obesity in these breeds.

  7. Lifestyle modification and behavior therapy effectively reduce body weight and increase serum level of brain-derived neurotrophic factor in obese non-diabetic patients with schizophrenia.

    PubMed

    Kuo, Feng-Chih; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Kuo, Philip; Chen, Yi-Chyan; Hung, Yi-Jen

    2013-09-30

    The goal of the study was to elucidate the relationship between serum circulating brain-derived neurotrophic factor (BDNF) and body weight reduction via lifestyle modification and behavior therapy in obese non-diabetic patients with chronic schizophrenia. Thirty-three obese non-diabetic subjects with schizophrenia treated with stable antipsychotic medication in a day-care unit for at least 3 months were recruited. Thirty age-, body weight-matched subjects without psychiatric disorders were enrolled as controls. All participants underwent a 10-week weight reduction program, including lifestyle modification, psychosocial treatment, behavior therapy and exercise in the day-care unit. Blood biochemistry, serum BDNF, adipokine (adiponectin), inflammatory markers (C-reactive protein, tumor necrosis factor-alpha and interleukin-6) and oral glucose tolerance test were evaluated before and after the program. Serum BDNF concentrations were significantly lower among patients with schizophrenia compared to control subjects. Serum BDNF levels were significantly increased following the weight reduction program. Elevations in serum BDNF levels were positively correlated with body weight and body mass index reduction. Altogether, our results demonstrate that a non-pharmacological weight reduction program effectively reduces body weight with significant elevation of serum BDNF levels in obese non-diabetic patients with schizophrenia.

  8. Preventive Effect of Boiogito on Metabolic Disorders in the TSOD Mouse, a Model of Spontaneous Obese Type II Diabetes Mellitus.

    PubMed

    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.

  9. Controlled downregulation of the cannabinoid CB1 receptor provides a promising approach for the treatment of obesity and obesity-derived type 2 diabetes.

    PubMed

    Lu, Dai; Dopart, Rachel; Kendall, Debra A

    2016-01-01

    Increased activity of the endocannabinoid system has emerged as a pathogenic factor in visceral obesity, which is a risk factor for type 2 diabetes mellitus (T2DM). The endocannabinoid system is composed of at least two Gprotein-coupled receptors (GPCRs), the cannabinoid receptor type 1 (CB1), and the cannabinoid receptor type 2 (CB2). Downregulation of CB1 activity in rodents and humans has proven efficacious to reduce food intake, abdominal adiposity, fasting glucose levels, and cardiometabolic risk factors. Unfortunately, downregulation of CB1 activity by universally active CB1 inverse agonists has been found to elicit psychiatric side effects, which led to the termination of using globally active CB1 inverse agonists to treat diet-induced obesity. Interestingly, preclinical studies have shown that downregulation of CB1 activity by CB1 neutral antagonists or peripherally restricted CB1 inverse agonists provided similar anorectic effects and metabolic benefits without psychiatric side effects seen in globally active CB1 inverse agonists. Furthermore, downregulation of CB1 activity may ease endoplasmic reticulum and mitochondrial stress which are contributors to obesity-induced insulin resistance and type 2 diabetes. This suggests new approaches for cannabinoid-based therapy in the management of obesity and obesity-related metabolic disorders including type 2 diabetes.

  10. Genetic vulnerability to diabetes and obesity: does education offset the risk?

    PubMed

    Liu, S Y; Walter, S; Marden, J; Rehkopf, D H; Kubzansky, L D; Nguyen, T; Glymour, M M

    2015-02-01

    The prevalence of type 2 diabetes (T2D) and obesity has recently increased dramatically. These common diseases are likely to arise from the interaction of multiple genetic, socio-demographic and environmental risk factors. While previous research has found genetic risk and education to be strong predictors of these diseases, few studies to date have examined their joint effects. This study investigates whether education modifies the association between genetic background and risk for type 2 diabetes (T2D) and obesity. Using data from non-Hispanic Whites in the Health and Retirement Study (HRS, n = 8398), we tested whether education modifies genetic risk for obesity and T2D, offsetting genetic effects; whether this effect is larger for individuals who have high risk for other (unobserved) reasons, i.e., at higher quantiles of HbA1c and BMI; and whether effects differ by gender. We measured T2D risk using Hemoglobin A1c (HbA1c) level, and obesity risk using body-mass index (BMI). We constructed separate genetic risk scores (GRS) for obesity and diabetes respectively based on the most current available information on the single nucleotide polymorphism (SNPs) confirmed as genome-wide significant predictors for BMI (29 SNPs) and diabetes risk (39 SNPs). Linear regression models with years of schooling indicate that the effect of genetic risk on HbA1c is smaller among people with more years of schooling and larger among those with less than a high school (HS) degree compared to HS degree-holders. Quantile regression models show that the GRS × education effect systematically increased along the HbA1c outcome distribution; for example the GRS × years of education interaction coefficient was -0.01 (95% CI = -0.03, 0.00) at the 10th percentile compared to -0.03 (95% CI = -0.07, 0.00) at the 90th percentile. These results suggest that education may be an important socioeconomic source of heterogeneity in responses to genetic vulnerability to T2D.

  11. [Overweight, obesity, diabetes, and hypertension in endometrial cancer].

    PubMed

    Sanz-Chávez, Tania L N; Vilar-Compte, Diana; de Nicola-Delfín, Luigina; Meneses-García, Abelardo

    2013-01-01

    Introducción: en mujeres posmenopáusicas, el exceso de grasa ha sido asociado con un incremento del riesgo de padecer cáncer de endometrio. El objetivo del estudio fue conocer la frecuencia de sobrepeso, obesidad, diabetes e hipertensión en pacientes con cáncer de endometrio. Métodos: se obtuvieron datos demográficos, clínicos, de laboratorio e histopatológicos de los expedientes electrónicos de las pacientes con diagnóstico de cáncer de endometrio en el periodo comprendido de enero del 2009 a julio del 2011. Posteriormente, se efectuó un análisis descriptivo de la información. Resultados: se incluyó un total de 274 expedientes. El promedio de edad de las pacientes fue de 54 años. El 50.4 % eran posmenopáusicas. En el momento del diagnóstico, 112 casos (48.6 %) se encontraban en etapa clínica I. Del total de pacientes, 104 (37.9 %) presentaron diabetes mellitus, 122 (44.5 %) hipertensión arterial, 194 (72.6 %) sobrepeso u obesidad, y se registraron 24 casos con síndrome metabólico. Conclusiones: para este diagnóstico, los resultados muestran un mayor número de casos de sobrepeso y obesidad en comparación con otros países. Es necesario que se hagan más estudios para evaluar la relación del exceso de grasa como factor de riesgo para el cáncer de endometrio.

  12. Association between metabolic syndrome, obesity, diabetes mellitus and oncological outcomes of bladder cancer: a systematic review.

    PubMed

    Cantiello, Francesco; Cicione, Antonio; Salonia, Andrea; Autorino, Riccardo; De Nunzio, Cosimo; Briganti, Alberto; Gandaglia, Giorgio; Dell'Oglio, Paolo; Capogrosso, Paolo; Damiano, Rocco

    2015-01-01

    Metabolic syndrome is a cluster of several metabolic abnormalities, its prevalence is increasing worldwide. To summarize the most recent evidence regarding the relationship between metabolic syndrome, its components and the oncological outcomes in bladder cancer patients, a National Center for Biotechnology Information PubMed search for relevant articles either published or e-published up to March 2014 was carried out by combining the following Patient population, Intervention, Comparison, Outcome terms: metabolic syndrome, obesity, body mass index, hyperglycemia, insulin resistance, diabetes, hypertension, dyslipidemia, bladder cancer, risk, mortality, cancer specific survival, disease recurrence and progression. Metabolic syndrome is a complex, highly prevalent disorder, and central obesity, insulin resistance, dyslipidemia and hypertension are its main components. Published findings would suggest that metabolic syndrome per se might be associated with an increased risk of bladder cancer in male patients, but it did not seem to confer a risk of worse prognosis. Considering the primary components of metabolic syndrome (hypertension, obesity and dyslipidemia), available data are uncertain, and it is no possible to reach a conclusion yet on either a direct or an indirect association with bladder cancer risk and prognosis. Only with regard to type 2 diabetes mellitus, available data would suggest a potential negative correlation. However, as the evaluation of bladder cancer risk and prognosis in patients with metabolic disorders is certainly complex, further studies are urgently required to better assess the actual role of these metabolic disorders.

  13. Vascular health in children and adolescents: effects of obesity and diabetes.

    PubMed

    Short, Kevin R; Blackett, Piers R; Gardner, Andrew W; Copeland, Kenneth C

    2009-01-01

    The foundations for cardiovascular disease in adults are laid in childhood and accelerated by the presence of comorbid conditions, such as obesity, diabetes, hypertension, and dyslipidemia. Early detection of vascular dysfunction is an important clinical objective to identify those at risk for subsequent cardiovascular morbidity and events, and to initiate behavioral and medical interventions to reduce risk. Typically, cardiovascular screening is recommended for young adults, especially in people with a family history of cardiovascular conditions. Children and adolescents were once considered to be at low risk, but with the growing health concerns related to sedentary lifestyle, poor diet and obesity, cardiovascular screening may be needed earlier so that interventions to improve cardiovascular health can be initiated. This review describes comorbid conditions that increase cardiovascular risk in youth, namely obesity and diabetes, and describes noninvasive methods to objectively detect vascular disease and quantify vascular function and structure through measurements of endothelial function, arterial compliance, and intima-media thickness. Additionally, current strategies directed toward prevention of vascular disease in these populations, including exercise, dietary interventions and pharmacological therapy are described.

  14. Effect of magnesium ion supplementation on obesity and diabetes mellitus in Otsuka Long-Evans Tokushima Fatty (OLETF) rats under excessive food intake.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa

    2013-01-01

    Several epidemiologic studies have found that magnesium ion (Mg²⁺) is related to obesity and type 2 diabetes mellitus. However, there have been almost no reports on the effects of a combination of excessive food intake and Mg²⁺ supplementation on metabolic syndrome and various blood tests values for diabetes mellitus. In this study, we investigated changes in body weight and blood test values for diabetes mellitus of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for human type 2 diabetes mellitus via metabolic syndrome, under conditions of combined excessive food intake and Mg²⁺ supplementation. The rats received Mg²⁺ supplementation by drinking magnesium water (Mg²⁺; 200 mg/l). No significant differences were observed in the levels of food or water intake between OLETF rats drinking purified water (PW) or magnesium water (MW). Type 2 diabetes mellitus with metabolic syndrome developed at 30 weeks of age, and the body weights and plasma insulin levels of OLETF rats at 60 weeks of age were lower than those of normal rats. The plasma glucose (PG) levels in 38-week-old OLETF rats drinking MW were significantly lower than in those of rats drinking PW, while the body weights and the levels of triglycerides (TG) and insulin of 38-week-old MW-drinking OLETF rats were significantly higher than those of their PW-drinking counterparts. On the other hand, the decreases in body weight and insulin levels in 60-week-old OLETF rats were suppressed by MW supplementation. The present study demonstrates that Mg²⁺ supplementation delays the development of diabetes mellitus in OLETF rats under conditions of excessive food intake. In addition, obesity and high blood TG levels were observed in OLETF rats receiving Mg²⁺ supplementation in conjunction with excessive food intake.

  15. 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

  16. Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome.

    PubMed

    Wimalawansa, Sunil J

    2016-09-20

    The aim of this study is to determine the relationships of vitamin D with diabetes, insulin resistance obesity, and metabolic syndrome. Intra cellular vitamin D receptors and the 1-α hydroxylase enzyme are distributed ubiquitously in all tissues suggesting a multitude of functions of vitamin D. It plays an indirect but an important role in carbohydrate and lipid metabolism as reflected by its association with type 2 diabetes (T2D), metabolic syndrome, insulin secretion, insulin resistance, polycystic ovarian syndrome, and obesity. Peer-reviewed papers, related to the topic were extracted using key words, from PubMed, Medline, and other research databases. Correlations of vitamin D with diabetes, insulin resistance and metabolic syndrome were examined for this evidence-based review. In addition to the well-studied musculoskeletal effects, vitamin D decreases the insulin resistance, severity of T2D, prediabetes, metabolic syndrome, inflammation, and autoimmunity. Vitamin D exerts autocrine and paracrine effects such as direct intra-cellular effects via its receptors and the local production of 1,25(OH)2D3, especially in muscle and pancreatic β-cells. It also regulates calcium homeostasis and calcium flux through cell membranes, and activation of a cascade of key enzymes and cofactors associated with metabolic pathways. Cross-sectional, observational, and ecological studies reported inverse correlations between vitamin D status with hyperglycemia and glycemic control in patients with T2D, decrease the rate of conversion of prediabetes to diabetes, and obesity. However, no firm conclusions can be drawn from current studies, because (A) studies were underpowered; (B) few were designed for glycemic outcomes, (C) the minimum (or median) serum 25(OH) D levels achieved are not measured or reported; (D) most did not report the use of diabetes medications; (E) some trials used too little (F) others used too large, unphysiological and infrequent doses of vitamin D; and (G

  17. Are frequency and severity of sleep-disordered breathing in obese children and youth with and without type 2 diabetes mellitus different?

    PubMed

    Shalitin, Shlomit; Tauman, Riva; Meyerovitch, Joseph; Sivan, Yakov

    2014-10-01

    Obstructive sleep apnea (OSA) is a risk factor for insulin resistance and type 2 diabetes mellitus (T2DM) in adults. Data in children are limited. The aim was to study the frequency and severity of OSA and its association with cardiometabolic risk factors in obese children and adolescents with and without T2DM. In this prospective cross-sectional study, obese children and adolescents with and without T2DM underwent polysomnography and blood tests for fasting lipids, insulin, glucose, liver functions, and C-reactive protein. All participants completed a questionnaire on past and present sleep-disordered breathing (SDB). Results were compared between T2DM and obese non-diabetic controls matched for body mass index-standard deviation score (BMI-SDS) and also according to the glycemic status: T2DM, impaired glucose tolerance (IGT), and normal glycemic control. Eleven patients with T2DM (age 15.9 ± 3.6 years) and 30 BMI-SDS matched non-diabetic subjects (age 12.7 ± 3.0 years) were studied. Among the entire cohort, 45 % had a history of snoring, 26 % reported apneic episodes during sleep, and 65 % had daytime fatigue. There were no significant between-group differences in SDB history or abnormal polysomnographic results [apnea-hypopnea index (AHI) >5/h]. The percentage of subjects with AHI >5/h was 45.5 % in T2DM patients, 25 % in obese patients with IGT, and 18.2 % in obese patients without IGT, although the difference was not statistically significant (p = 0.25). Plasma C-reactive protein levels were related to both glycemic status and OSA severity. The severity of OSA in obese children and adolescents is unrelated to the presence of diabetes. OSA may play a minor role in the development and progression of T2DM in children and adolescents. Further studies in larger cohorts are required.

  18. Rationale and design of the Early Sleeve gastrectomy In New Onset Diabetic Obese Patients (ESINODOP) trial.

    PubMed

    Trastulli, Stefano; Desiderio, Jacopo; Grandone, Ilenia; Fontana, Lucia; Paolini, Luisa; Altomare, Maria; D'Angelo, Paola; Palazzi, Mariangela; Cirocchi, Roberto; Leotta, Sergio; Fatati, Giuseppe; Parisi, Amilcare

    2017-03-01

    No randomized clinical trials (RCTs) have yet evaluated the bariatric surgery's efficacy and safety in patients newly diagnosed with type 2 diabetes mellitus (T2DM). The aim of this multicenter RCT is to compare bariatric surgery, particularly laparoscopic sleeve gastrectomy (LSG), with conventional medical therapy (CMT) in obese patients (body mass index between 30 and 42 kg/m(2)) newly diagnosed with T2DM and without any diabetes-related complications at any stage. A total of 100 eligible patients will be randomized at a 1:1 ratio to undergo one of the two planned treatments and will be followed for at least 6 years after randomization. The main objective of the ESINODOP trial is to investigate the efficacy of LSG compared with CMT alone in inducing and maintaining a remission of T2DM (defined as HbA1c levels ≤6.0 %, without active pharmacologic therapy after 1 year). The remission of T2DM will also be evaluated with the criteria provided by the American Diabetes Association (ADA), and the additional parameters such as adverse event rates, micro- and macrovascular complications, weight loss, gastrointestinal hormones, and quality of life will be compared. The study started on September 2015 and the planned recruitment period is 3 years. Patient recruitment and follow-up take place in the two diabetology and nutrition centers participating in the study, which are performed on a national basis. The ESINODOP trial is designed with the intent of comparing the efficacy of CMT alone to that of CMT in conjunction with LSG performed at the time of diabetes diagnosis in mildly obese diabetic patients. Currently, patients with these characteristics are not eligible for bariatric/metabolic surgery.

  19. 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.

  20. [Possibilities of behavior modification in the treatment of diabetes mellitus and obesity].

    PubMed

    Sal, István; Papp, Ildikó; Perczel Forintos, Dóra

    2012-03-18

    Being aware of the worldwide spread of diabetes and obesity as well as its economic effects, the authors discuss the complex, behavior remediational methods of the treatment and its current questions. They emphasize the role of chronic stress in the etiopatogenesis of insulin resistance, metabolic syndrome, and type 2 diabetes. All these require a shift of paradigm in the field of treatment too. Based on literature data and on their own practical experience, the authors consider that behavior remediational can integrate two, sometimes still opposing medical philosophical views in order to foster the efficiency of medical work. They review elements of behavior remediation of diabetes, underlining self-management, acceptance of the illness, and motivation which can be followed by teaching theoretical and practical knowledge, the ongoing diabetes education. Comorbid psychological disorders impede these processes; their early recognition and complex treatment are essential. The authors present a cognitive, behavior remediational programme of weight loss, that can be used in practise, both in prevention and treatment of diabetes.

  1. 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

  2. Hepatic CREB3L3 controls whole-body energy homeostasis and improves obesity and diabetes.

    PubMed

    Nakagawa, Yoshimi; Satoh, Aoi; Yabe, Sachiko; Furusawa, Mika; Tokushige, Naoko; Tezuka, Hitomi; Mikami, Motoki; Iwata, Wakiko; Shingyouchi, Akiko; Matsuzaka, Takashi; Kiwata, Shiori; Fujimoto, Yuri; Shimizu, Hidehisa; Danno, Hirosuke; Yamamoto, Takashi; Ishii, Kiyoaki; Karasawa, Tadayoshi; Takeuchi, Yoshinori; Iwasaki, Hitoshi; Shimada, Masako; Kawakami, Yasushi; Urayama, Osamu; Sone, Hirohito; Takekoshi, Kazuhiro; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Yamada, Nobuhiro; Shimano, Hitoshi

    2014-12-01

    Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis during starvation. The membrane-bound transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3) has been reported to be activated during fasting and to regulate triglyceride metabolism. Here, we show that CREB3L3 confers a wide spectrum of metabolic responses to starvation in vivo. Adenoviral and transgenic overexpression of nuclear CREB3L3 induced systemic lipolysis, hepatic ketogenesis, and insulin sensitivity with increased energy expenditure, leading to marked reduction in body weight, plasma lipid levels, and glucose levels. CREB3L3 overexpression activated gene expression levels and plasma levels of antidiabetic hormones, including fibroblast growth factor 21 and IGF-binding protein 2. Amelioration of diabetes by hepatic activation of CREB3L3 was also observed in several types of diabetic obese mice. Nuclear CREB3L3 mutually activates the peroxisome proliferator-activated receptor (PPAR) α promoter in an autoloop fashion and is crucial for the ligand transactivation of PPARα by interacting with its transcriptional regulator, peroxisome proliferator-activated receptor gamma coactivator-1α. CREB3L3 directly and indirectly controls fibroblast growth factor 21 expression and its plasma level, which contributes at least partially to the catabolic effects of CREB3L3 on systemic energy homeostasis in the entire body. Therefore, CREB3L3 is a therapeutic target for obesity and diabetes.

  3. Inadequate sleep as a contributor to obesity and type 2 diabetes.

    PubMed

    McNeil, Jessica; Doucet, Éric; Chaput, Jean-Philippe

    2013-04-01

    Epidemiological studies suggest that adults and children who are habitual short sleepers tend to have a higher body mass index, fat percentage and abdominal circumference when compared to average-duration sleepers. Reduced or disturbed sleep is also associated with certain predictors of type 2 diabetes, such as glucose intolerance, insulin resistance, reduced insulin response to glucose and a reduction in the disposition index. Current experimental evidence suggests that sleep restriction may lead to increased food intake but does not appear to result in decreased energy expenditure. Furthermore, sleep restriction has been reported to increase evening cortisol levels, which may decrease insulin sensitivity the next morning. This notion was further supported by studies, which noted decreases in the effectiveness of insulin-mediated glucose uptake the following morning. Further evidence suggests that short sleepers have glucose responses that are similar to average-duration sleepers, but at the cost of an increase in insulin release, which may be the result of decreased insulin sensitivity over time. Recent studies also provide evidence that sleep restriction enhances susceptibility to food stimuli, especially for energy-dense, high-carbohydrate foods. In summary, inadequate sleep, in both quality and quantity, should be regarded as a plausible risk factor for the development of obesity and type 2 diabetes. In addition to other health promotion measures, a good night's sleep should be seen as a critical health component by clinicians in the prevention and treatment of obesity and type 2 diabetes.

  4. Red raspberry (Rubus idaeus L.) intake decreases oxidative stress in obese diabetic (db/db) mice.

    PubMed

    Noratto, Giuliana D; Chew, Boon P; Atienza, Liezl M

    2017-07-15

    Red raspberry fruit intake was investigated on obese diabetic (db/db) mice for 8weeks. Animals fed isocaloric diets (5.3% freeze-dried raspberry, or control) were assessed for obesity-diabetes-disease risk biomarkers. Results showed that raspberry intake improved antioxidant status and lessened plasma interleukin (IL)-6 (0.3-fold of control, p<0.1); most likely through enhancing glutathione peroxidase (GPx) activity in liver (4.3-fold of control), and in blood (2.1-fold of control). Other disease-risk biomarkers were similar between groups (p>0.05). Plasma levels of total cholesterol (T-CHL), low density lipoprotein-cholesterol (LDL-CHL), and resistin were higher in the raspberry group. Overall, the enhanced detoxifying cell defenses exerted by raspberry intake might be due to its polyphenolics and fibre. This study demonstrates in vivo that raspberry intake, at a dose that can be achieved by human consumption, might protect against diabetes-induced oxidative stress.

  5. [Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome].

    PubMed

    Halmos, Tamás; Suba, Ilona

    2016-01-03

    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

  6. 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.

  7. 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

  8. Does obesity influence labour market outcomes among working-age adults? Evidence from Canadian longitudinal data.

    PubMed

    Larose, Samantha L; Kpelitse, Koffi A; Campbell, M Karen; Zaric, Gregory S; Sarma, Sisira

    2016-03-01

    Although a negative association between obesity and labour market outcomes is commonly reported in many studies, the causal nature of this relationship remains unclear. Using nationally representative longitudinal data from the last six confidential master files (2000/2001-2010/2011) of the National Population Health Survey, we examine the association between obesity and employment participation and earnings among working-age adults in Canada. After controlling for demographic and socioeconomic characteristics, lifestyle factors and time-invariant individual heterogeneity, our results show that obesity is not significantly associated with employment participation but is associated with reduced hourly wage rate and annual income among women by about 4% and 4.5%, respectively. The corresponding results for men show that obesity is associated with about 2% reduction in wage rate and income, but significant at 10% level. However, after controlling for the potential reverse causality bias using the lagged measure of obesity, the effect of obesity on wage rate and income became positive or statistically non-significant. Our findings suggest that obesity is not causally associated with negative labour market outcomes among working-age men in Canada. For working-age women, we find limited evidence of negative labour market outcomes.

  9. Naltrexone/bupropion for the treatment of obesity and obesity with Type 2 diabetes.

    PubMed

    Apovian, Caroline M

    2016-03-01

    Contrave(®) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, and is used with lifestyle modification. Its safety and efficacy were assessed in four randomized, double-blind, placebo-controlled, 56-week Phase III clinical trials in 4536 adult subjects: COR-1, COR-II, COR-BMOD and COR-DM. All four studies demonstrated statistically significant and clinically meaningful weight loss following up to 52 weeks of treatment with naltrexone/bupropion compared with placebo. The average weight loss from baseline across the four studies was approximately 11-22 lbs (5-9 kg). Results show the efficacy of Contrave for weight loss, as well as significant improvements in cardiometabolic markers. This review focuses on the four studies, their outcomes and the mechanism of action of Contrave.

  10. Combined Anti-Inflammatory and Anti-AGE Drug Treatments Have a Protective Effect on Intervertebral Discs in Mice with Diabetes

    PubMed Central

    Illien-Junger, Svenja; Grosjean, Fabrizio; Laudier, Damien M.; Vlassara, Helen; Striker, Gary E.; Iatridis, James C.

    2013-01-01

    Objective Diabetes and low back pain are debilitating diseases and modern epidemics. Diabetes and obesity are also highly correlated with intervertebral disc (IVD) degeneration and back pain. Advanced-glycation-end-products (AGEs) increase reactive-oxygen-species (ROS) and inflammation, and are one cause for early development of diabetes mellitus. We hypothesize that diabetes results in accumulation of AGEs in spines and associated spinal pathology via increased catabolism. We present a mouse model showing that: 1) diabetes induces pathological changes to structure and composition of IVDs and vertebrae; 2) diabetes is associated with accumulation of AGEs, TNFα, and increased catabolism spinal structures; and 3) oral-treatments with a combination of anti-inflammatory and anti-AGE drugs mitigate these diabetes-induced degenerative changes to the spine. Methods Three age-matched groups of ROP-Os mice were compared: non-diabetic, diabetic (streptozotocin (STZ)-induced), or diabetic mice treated with pentosan-polysulfate (anti-inflammatory) and pyridoxamine (AGE-inhibitor). Mice were euthanized and vertebra-IVD segments were analyzed by μCT, histology and Immunohistochemistry. Results Diabetic mice exhibited several pathological changes including loss in IVD height, decreased vertebral bone mass, decreased glycosaminoglycan content and morphologically altered IVDs with focal deposition of tissues highly expressing TNFα, MMP-13 and ADAMTS-5. Accumulation of larger amounts of methylglyoxal suggested that AGE accumulation was associated with these diabetic degenerative changes. However, treatment prevented or reduced these pathological effects on vertebrae and IVD. Conclusion This is the first study to demonstrate specific degenerative changes to nucleus pulposus (NP) morphology and their association with AGE accumulation in a diabetic mouse model. Furthermore, this is the first study to demonstrate that oral-treatments can inhibit AGE-induced ROS and inflammation in

  11. Intergenerational Cycle of Obesity and Diabetes: How Can We Reduce the Burdens of These Conditions on the Health of Future Generations?

    PubMed Central

    Battista, Marie-Claude; Hivert, Marie-France; Duval, Karine; Baillargeon, Jean-Patrice

    2011-01-01

    Prepregnancy overweight or obesity and excessive gestational weight gain have been associated with increased risk of maternal and neonatal complications. Moreover, offspring from obese women are more likely to develop obesity, diabetes mellitus, and cardiovascular diseases in their lifetime. Gestational diabetes mellitus (GDM) is one of the most common complications associated with obesity and appears to have a direct impact on the future metabolic health of the child. Fetal programming of metabolic function induced by obesity and GDM may have intergenerational effect and thus perpetuate the epidemic of cardiometabolic conditions. The present paper thus aims at discussing the impact of maternal obesity and GDM on the developmental programming of obesity and metabolic disorders in the offspring. The main interventions designed to reduce maternal obesity and GDM and their ability to break the vicious circle that perpetuates the transmission of obesity and metabolic conditions to the next generations are also addressed. PMID:22110473

  12. 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

  13. 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

  14. Inhibition of advanced glycation end products (AGEs): an implicit goal in clinical medicine for the treatment of diabetic nephropathy?

    PubMed

    Miyata, Toshio; Dan, Takashi

    2008-11-13

    Several factors are incriminated in the genesis of diabetic nephropathy (DN). To elucidate their interplays, we utilized a diabetic rat model with nephropathy (SHR/NDmcr-cp). This model is characterized by hypertension, obesity with the metabolic syndrome, diabetes with insulin resistance, and intrarenal AGE accumulation. Various therapeutic approaches were used to achieve renoprotection. Caloric restriction corrects metabolic abnormalities and protects the kidney without correcting hypertension. Anti-hypertensive agents, angiotensin II receptor blocker (ARB) and calcium channel blocker, lower blood pressure to the same extent, but only ARBs protect the kidney without changes in metabolic abnormalities. Glycemic control is better with insulin than with pioglitazone. The plasma insulin level is increased by insulin but decreased by pioglitazone which worsens the obesity. Nevertheless, pioglitazone provides renoprotection unlike insulin, perhaps as a result of the up-regulation of TGF-beta by hyperinsulinemia. Cobalt up-regulates the expression of a hypoxia-inducible factor (HIF) and its downstream genes (erythropoietin, VEGF, HO-1). It protects the kidney without correcting hypertension and metabolic abnormalities. Altogether, renoprotection is not necessarily associated with blood pressure or glycemic control. By contrast, it is almost always associated with a decreased AGE formation. AGE reduction may reflect a decreased oxidative stress as it is concomitant with a marked reduction of oxidative stress markers.

  15. Depletion of IL-2 receptor β-positive cells protects from diabetes in non-obese diabetic mice.

    PubMed

    Brauner, Hanna; Hall, Håkan T; Flodström-Tullberg, Malin; Kärre, Klas; Höglund, Petter; Johansson, Sofia

    2016-02-01

    The destruction of β-cells in type 1 diabetes (T1D) progresses silently until only a minor fraction of the β-cells remain. A late acting therapy leading to the prevention of further β-cell killing would therefore be desirable. CD122, the β chain of the interleukin-2 receptor, is highly expressed on natural killer (NK) cells and on a subpopulation of CD8 T cells. In this study, we have treated non-obese diabetic (NOD) mice with a depleting antibody against CD122. The treatment protected from diabetes, even when initiated just before disease onset. The degree of leukocyte infiltration into islets was unaffected by the treatment, further supporting effectiveness late in the disease process. It effectively removed all NK cells from the spleen, pancreas and pancreatic lymph nodes and abolished NK cell activity. Interestingly, despite the lack of CD122 expression on CD8 T cells in the pancreas, the overall frequency of CD8 cells decreased in this organ, whereas it was unaffected in the spleen. T cells were also still capable to respond against a foreign antigen. Conclusively, targeting of CD122(+) cells could represent a novel treatment strategy against T1D.

  16. The natural killer T lymphocyte: a player in the complex regulation of autoimmune diabetes in non-obese diabetic mice

    PubMed Central

    Cardell, S L

    2006-01-01

    Manipulation of the immune response to specifically prevent autoaggression requires an understanding of the complex interactions that occur during the pathogenesis of autoimmunity. Much attention has been paid to conventional T lymphocytes recognizing peptide antigens presented by classical major histocompatibility complex (MHC) class I and II molecules, as key players in the destructive autoreactive process. A pivotal role for different types of regulatory T lymphocytes in modulating the development of disease is also well established. Lately, CD1d-restricted natural killer T (NKT) lymphocytes have been the subject of intense investigation because of their ability to regulate a diversity of immune responses. The non-classical antigen presenting molecule CD1d presents lipids and glycolipids to this highly specialized subset of T lymphocytes found in both humans and mice. From experimental models of autoimmunity, evidence is accumulating that NKT cells can protect from disease. One of the best studied is the murine type 1 diabetes model, the non-obese diabetic (NOD) mouse. While the NKT cell population was first recognized to be deficient in NOD mice, augmenting NKT cell activity has been shown to suppress the development of autoimmune disease in this strain. The mechanism by which CD1d-restricted T cells exert this function is still described incompletely, but investigations in NOD mice are starting to unravel specific effects of NKT cell regulation. This review focuses on the role of CD1d-restricted NKT cells in the control of autoimmune diabetes. PMID:16412042

  17. 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

  18. 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 ...

  19. Involvement of splenic iron accumulation in the development of nonalcoholic steatohepatitis in Tsumura Suzuki Obese Diabetes mice

    PubMed Central

    Murotomi, Kazutoshi; Arai, Shigeyuki; Uchida, Satoko; Endo, Shin; Mitsuzumi, Hitoshi; Tabei, Yosuke; Yoshida, Yasukazu; Nakajima, Yoshihiro

    2016-01-01

    Nonalcoholic steatohepatitis (NASH) is a common hepatic manifestation of metabolic syndrome and can lead to hepatic cirrhosis and cancer. It is considered that NASH is caused by multiple parallel events, including abnormal lipid metabolism, gut-derived-endotoxin-induced inflammation, and adipocytokines derived from adipose tissue, suggesting that other tissues are involved in NASH development. Previous studies demonstrated that spleen enlargement is observed during the course of NASH pathogenesis. However, the involvement of splenic status in the progression of NASH remains unclear. In this study, we examined hepatic and splenic histopathological findings in the early stage of NASH using the Tsumura Suzuki Obese Diabetes (TSOD) mouse model established for assessing NASH. We found that 12-week-old TSOD mice clearly exhibited the histopathological features of NASH in the early stage. At this age, the spleen of TSOD mice showed markedly higher iron level than that of control Tsumura Suzuki Non Obesity (TSNO) mice. The level of accumulated iron was significantly decreased by feeding a diet with glucosyl hesperidin, a bioactive flavonoid, accompanied with alleviation of hepatic lesions. Furthermore, we found that splenic iron level was positively correlated with the severity of NASH manifestations, suggesting that abnormalities in the spleen are involved in the development of NASH. PMID:26932748

  20. Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography.

    PubMed

    Kerckhofs, G; Durand, M; Vangoitsenhoven, R; Marin, C; Van der Schueren, B; Carmeliet, G; Luyten, F P; Geris, L; Vandamme, K

    2016-10-19

    High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging.

  1. Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography

    NASA Astrophysics Data System (ADS)

    Kerckhofs, G.; Durand, M.; Vangoitsenhoven, R.; Marin, C.; van der Schueren, B.; Carmeliet, G.; Luyten, F. P.; Geris, L.; Vandamme, K.

    2016-10-01

    High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging.

  2. Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography

    PubMed Central

    Kerckhofs, G.; Durand, M.; Vangoitsenhoven, R.; Marin, C.; Van der Schueren, B.; Carmeliet, G.; Luyten, F. P.; Geris, L.; Vandamme, K.

    2016-01-01

    High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging. PMID:27759061

  3. What Is the Best NGS Enrichment Method for the Molecular Diagnosis of Monogenic Diabetes and Obesity?

    PubMed Central

    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

  4. Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy.

    PubMed

    Isidro, M Luisa; Penín, Manuel A; Nemiña, Rosa; Cordido, Fernando

    2007-08-01

    Context It has been reported that metformin might modify thyroid hormone economy. In two retrospective studies, initiation of treatment with metformin caused suppression of TSH to subnormal levels. Objective To prospectively evaluate if administration of metformin to obese, diabetic patients with primary hypothyroidism on stable thyroxine replacement doses modifies TSH levels. Patients and methods Eight obese, diabetic postmenopausal women with primary hypothyroidism participated in the study. They received 1,700 mg of metformin daily for 3 months. Weight, TSH, free T4, and free T3 levels were measured at baseline, 3 months after metformin initiation and 3 months after its withdrawal. Results After 3 months of on metformin, mean TSH was significantly lower than basal TSH (3.11 +/- 0.50 microUI/ml vs. 1.18 +/- 0.36 microUI/ml; P = 0.01). Mean TSH 3 months after metformin withdrawal was 2.21 +/- 0.37 microUI/ml, significantly higher than TSH after metformin (P = 0.05), but not different from basal TSH. Mean fT4 level increased during metformin administration (basal fT4: 1.23 +/- 0.06 ng/dl, fT4 after metformin: 1.32 +/- 0.04 ng/dl; P = ns), and decreased after its withdrawal (fT4 3 months after metformin withdrawal: 1.15 +/- 0.05 ng/dl; vs. 3 months after metformin, P = 0.04; vs. basal; P = ns). Conclusions In obese, diabetic patients with primary hypothyroidism on thyroxine replacement treatment, short-term metformin administration is associated with a significant fall in TSH.

  5. 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

  6. Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity

    PubMed Central

    Yue, Jessica T. Y.; Abraham, Mona A.; Bauer, Paige V.; LaPierre, Mary P.; Wang, Peili; Duca, Frank A.; Filippi, Beatrice M.; Chan, Owen; Lam, Tony K. T.

    2016-01-01

    Impaired glucose homeostasis and energy balance are integral to the pathophysiology of diabetes and obesity. Here we show that administration of a glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the dorsal vagal complex (DVC) suppresses glucose production, increases glucose tolerance and reduces food intake and body weight gain in healthy, obese and diabetic rats. These findings provide proof of concept that GlyT1 inhibition in the brain improves glucose and energy homeostasis. Considering the clinical safety and efficacy of GlyT1 inhibitors in raising glycine levels in clinical trials for schizophrenia, we propose that GlyT1 inhibitors have the potential to be repurposed as a treatment of both obesity and diabetes. PMID:27874011

  7. Lipocalin-2 expression and serum levels as early predictors of type 2 diabetes mellitus in obese women.

    PubMed

    Rashad, Nearmeen M; El-Shal, Amal S; Etewa, Rasha L; Wadea, Fady M

    2017-02-01

    Obesity and diabetes are increasing in epidemic proportions globally. Lipocalin-2 (LCN-2) is an inflammatory adipocytokine and obesity-related marker of low-grade inflammation. We aimed to investigate, for first time, the possible role of LCN-2 expression and serum levels in prediction of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) among obese Egyptian women. This study included 188 obese women and 180 controls. Obese women were subdivided into three subgroups according to their fasting blood glucose, normal glucose tolerance (NGT), IGT and T2DM. Circulating LCN-2 expression levels were determined by real time polymerase chain reaction. Serum LCN-2 concentrations were assessed by ELISA. Our findings revealed that LCN-2 expression and serum levels were higher in obese women compared to lean controls. They were higher in IGT and T2DM obese cases than in NGT obese women. Receiver operating characteristic analyses revealed that LCN-2 expression level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.735 and 0.740, respectively). It was an independent predictor of IGT and T2DM among obese women. Serum LCN-2 level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.705 and 0.728, respectively). It was independent predictor of T2DM without predicting IGT among obese women. The power of combined LCN-2 serum levels and expression in discriminating between IGT from NGT and T2DM from IGT obese women was high (AUC = 0.717 and 0.741, respectively). In conclusion, LCN-2 expression and serum levels could discriminate IGT from NGT and T2DM from IGT obese women and early predicting T2DM among obese women. While, LCN-2 expression level was the independent predictor of IGT in obese women. Combination of both LCN-2 expression and serum levels improved their diagnostic value in early detection of IGT and T2DM among obese women. © 2017 IUBMB Life, 69(2):88-97, 2017.

  8. Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes

    PubMed Central

    Kahles, Florian; Findeisen, Hannes M.; Bruemmer, Dennis

    2014-01-01

    Since its first description more than 20 years ago osteopontin has emerged as an active player in many physiological and pathological processes, including biomineralization, tissue remodeling and inflammation. As an extracellular matrix protein and proinflammatory cytokine osteopontin is thought to facilitate the recruitment of monocytes/macrophages and to mediate cytokine secretion in leukocytes. Modulation of immune cell response by osteopontin has been associated with various inflammatory diseases and may play a pivotal role in the development of adipose tissue inflammation and insulin resistance. Here we summarize recent findings on the role of osteopontin in metabolic disorders, particularly focusing on diabetes and obesity. PMID:24944898

  9. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P.

    2000-06-27

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  10. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P.

    1998-01-01

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  11. Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.

    PubMed

    Frank, Graeme R; Fox, Joyce; Candela, Ninfa; Jovanovic, Zorica; Bochukova, Elena; Levine, Jeremiah; Papenhausen, Peter R; O'Rahilly, Stephen; Farooqi, I Sadaf

    2013-01-01

    Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.

  12. Relationship of cytokines and AGE products in diabetic and non-diabetic patients with cataract

    PubMed Central

    Hamid, Sadaf; Gul, Anjuman; Hamid, Qamar

    2016-01-01

    Objectives Cytokines are important mediators of inflammatory and immune responses. The aim of this study was to investigate the changes in cytokines concentration (IL-6, IL-8 and TNF-α) and serum advanced glycation end products (sAGEs) in senile diabetics with or without cataract and non-diabetic patients with cataract. Methodology The study included 124 subjects (sixty or over sixty years age), distributed as four groups thirty senile diabetic patients with cataract (Group I) (16 female and 14 male), thirty senile non-diabetic patients with cataract (Group II) (15 female and 15 male), thirty three senile diabetic patients without any complication (Group III) (16 female and 17 male), thirty one apparently normal healthy individuals (Group IV) (16 female and 15 male), age, sex and weight matched with senile control subjects were investigated. Patients were selected on clinical grounds from Eye Ward Jinnah Postgraduate Medical Centre. Results Interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) levels were significantly increased (P < 0.001) in Group I and III as compared to Group II and IV. Fasting blood glucose, glycosylated hemoglobin, serum fructosamine, malondialdehyde (MDA), sAGEs, IL-6, IL-8 and TNF-α levels were significantly increased (P < 0.001) in Group I as compared to Group II and the levels were almost same in Group II and IV. There was a significant decrease in serum vitamin E and total antioxidant status (p< 0.001) in Group I and Group III as compared to Group II and Group IV. Conclusion The results of the present study thus demonstrated that levels increased in both condition but are more severe in diabetic patients with cataract that may be a predictor for cataractogenesis and the levels were almost same in Group II and IV. PMID:27833515

  13. 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

  14. Higher glomerular filtration rate is related to insulin resistance but not to obesity in a predominantly obese non-diabetic cohort

    PubMed Central

    Naderpoor, Negar; Lyons, Jasmine G.; Mousa, Aya; Ranasinha, Sanjeeva; Courten, Maximilian P. J. de; Soldatos, Georgia; Courten, Barbora de

    2017-01-01

    Glomerular hyperfiltration has been associated with obesity, insulin resistance, and systolic blood pressure (SBP). However, previous studies are limited by confounders such as pre-existing diabetes or hypertension, or have used indirect measures of adiposity and insulin sensitivity (IS). Therefore, we examined the relationship between estimated glomerular filtration rate (eGFR) and IS measured by the hyperinsulinaemic euglycaemic clamp in a healthy population on no medications. We performed oral glucose tolerance test (OGTT) and measured % body fat (DEXA), BMI, blood pressure and M-value (hyperinsulinaemic euglycaemic clamp) in 104 individuals (44 females and 60 males). The majority of the study population (n = 89, 85.6%) were classified on their BMI as overweight/obese. eGFR was related to age, BMI, M-value (IS), 2-hour glucose levels post OGTT and white blood cell count (WBC) (all p < 0.05); but not to SBP (p = 0.1) or fasting glucose levels (p = 0.2). After adjustment for gender, BMI, SBP and WBC, the inverse association between eGFR and M-value (p = 0.001), and 2-hour glucose post OGTT (p = 0.02) persisted. In conclusion, although eGFR has been associated with BMI and blood pressure in previous studies, in our healthy population, eGFR was more closely related to markers of glucose metabolism (IS and 2-hour glucose post OGTT) than to BMI and blood pressure. PMID:28368024

  15. 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

  16. 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.

  17. Nonalcoholic fatty liver disease and type 2 diabetes in obese children.

    PubMed

    Hecht, Lior; Weiss, Ram

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is commonly found in adults and adolescents with type 2 diabetes (T2DM). The cause-effect relations of these 2 conditions are complex and it is difficult to decipher whether one drives the other or vice versa. Genetic predispositions, along with obesity, are probably shared culprits of both. NAFLD may precede the diagnosis of diabetes and play a critical role of driving its development by way of increasing hepatic and whole body insulin resistance. On the other hand, T2DM is associated with hyperinsulinemia, a resistance to some of the effects of gut derived peptides and increased systemic free fatty acids, that can all promote hepatic lipid deposition. Thus, each condition may promote the development of the other and their mutual presence creates a vicious cycle. Upon studying this complex interplay from another angle, reduction of liver fat significantly improves glucose metabolism in patients with T2DM highlighting the tight pathophysiological link between them.

  18. Aging, obesity, and post-therapy cognitive recovery in breast cancer survivors.

    PubMed

    Huang, Zhezhou; Zheng, Ying; Bao, Pingping; Cai, Hui; Hong, Zhen; Ding, Ding; Jackson, James; Shu, Xiao-Ou; Dai, Qi

    2016-10-11

    Therapy-induced cognitive impairment is prevalent and long-lasting in cancer survivors, but factors affecting post-therapy cognitive recovery are unclear. We conducted this study to evaluate the associations of age, body mass index (BMI), waist-to-hip ratio (WHR), and physical activity (PA) with post-therapy cognitive changes in a population-based breast cancer (BC) survivor cohort. We collected information on PA, weight, height, waist and hip circumferences of 1286 BC survivors aged 20-75. We assessed their cognitive functions, including immediate memory, delayed memory, verbal fluency, and attention, at 18 and 36 months after cancer diagnosis. Linear regression models were used to examine the associations of age, BMI, WHR and PA with mean changes in cognitive scores from 18- to 36-month follow-up interview. We found that the post-therapy cognitive changes differed by age and obesity status. Verbal fluency and attention improved in younger patients aged <60 and non-abdominally obese patients, but deteriorated in older patients aged ≥60 (i.e. verbal fluency and attention) and abdominally obese patients (i.e. verbal fluency). Memory improved in all patients, with a smaller improvement in obese patients compared with normal-weight patients. No significant association was found between PA and post-therapy cognitive change. Due to the novelty of our findings and the limitations of our study, further research, including intervention trials, is warranted to confirm the causal relationship between obesity and cognitive impairments.

  19. Postmaximal contraction blood volume responses are blunted in obese and type 2 diabetic subjects in a muscle-specific manner.

    PubMed

    Sanchez, Otto A; Copenhaver, Elizabeth A; Chance, Marti A; Fowler, Michael J; Towse, Theodore F; Kent-Braun, Jane A; Damon, Bruce M

    2011-08-01

    The purpose of this study was to determine whether there are differences in postisometric contraction blood volume and oxygenation responses among groups of type 2 diabetes mellitus (T2DM), obese, and lean individuals detectable using MRI. Eight T2DM patients were individually matched by age, sex, and race to non-T2DM individuals with similar body mass index (obese) and lean subjects. Functional MRI was performed using a dual-gradient-recalled echo, echo-planar imaging sequence with a repetition time of 1 s and at two echo times (TE = 6 and 46 ms). Data were acquired before, during, and after 10-s isometric dorsiflexion contractions performed at 50 and 100% of maximal voluntary contraction (MVC) force. MRI signal intensity (SI) changes from the tibialis anterior and extensor digitorum longus muscles were plotted as functions of time for each TE. From each time course, the difference between the minimum and the maximum postcontraction SI (ΔSI) were determined for TE = 6 ms (ΔSI(6)) and TE = 46 ms (ΔSI(46)), reflecting variations in blood volume and oxyhemoglobin saturation, respectively. Following 50% MVC contractions, the mean postcontraction ΔSI(6) values were similar in the three groups. Following MVC only, and in the EDL muscle only, T2DM and obese participants had ∼56% lower ΔSI(6) than the lean individuals. Also following MVC only, the ΔSI(46) response in the EDL was lower in T2DM subjects than in lean individuals. These data suggest that skeletal muscle small vessel impairment occurs in T2DM and body mass index-matched subjects, in muscle-specific and contraction intensity-dependent manners.

  20. Postmaximal contraction blood volume responses are blunted in obese and type 2 diabetic subjects in a muscle-specific manner

    PubMed Central

    Sanchez, Otto A.; Copenhaver, Elizabeth A.; Chance, Marti A.; Fowler, Michael J.; Towse, Theodore F.; Kent-Braun, Jane A.

    2011-01-01

    The purpose of this study was to determine whether there are differences in postisometric contraction blood volume and oxygenation responses among groups of type 2 diabetes mellitus (T2DM), obese, and lean individuals detectable using MRI. Eight T2DM patients were individually matched by age, sex, and race to non-T2DM individuals with similar body mass index (obese) and lean subjects. Functional MRI was performed using a dual-gradient-recalled echo, echo-planar imaging sequence with a repetition time of 1 s and at two echo times (TE = 6 and 46 ms). Data were acquired before, during, and after 10-s isometric dorsiflexion contractions performed at 50 and 100% of maximal voluntary contraction (MVC) force. MRI signal intensity (SI) changes from the tibialis anterior and extensor digitorum longus muscles were plotted as functions of time for each TE. From each time course, the difference between the minimum and the maximum postcontraction SI (ΔSI) were determined for TE = 6 ms (ΔSI6) and TE = 46 ms (ΔSI46), reflecting variations in blood volume and oxyhemoglobin saturation, respectively. Following 50% MVC contractions, the mean postcontraction ΔSI6 values were similar in the three groups. Following MVC only, and in the EDL muscle only, T2DM and obese participants had ∼56% lower ΔSI6 than the lean individuals. Also following MVC only, the ΔSI46 response in the EDL was lower in T2DM subjects than in lean individuals. These data suggest that skeletal muscle small vessel impairment occurs in T2DM and body mass index-matched subjects, in muscle-specific and contraction intensity-dependent manners. PMID:21572006

  1. Vitamin B12 Status among Pregnant Women in the UK and Its Association with Obesity and Gestational Diabetes

    PubMed Central

    Sukumar, Nithya; Venkataraman, Hema; Wilson, Sean; Goljan, Ilona; Selvamoni, Selvin; Patel, Vinod; Saravanan, Ponnusamy

    2016-01-01

    Background: To evaluate vitamin B12 and folate status in pregnancy and their relationship with maternal obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Methods: A retrospective case-control study of 344 women (143 GDM, 201 no-GDM) attending a district general hospital and that had B12 and folate levels measured in the early 3rd trimester was performed. Maternal history including early pregnancy body mass index (BMI) and neonatal data (birthweight, sex, and gestational age) was recorded for all subjects. Results: 26% of the cohort had B12 levels <150 pmol/L (32% vs. 22% in the two groups respectively, p < 0.05) while 1.5% were folate deficient. After adjusting for confounders, 1st trimester BMI was negatively associated with 3rd trimester B12 levels. Women with B12 insufficiency had higher odds of obesity and GDM (aOR (95% CI) 2.40 (1.31, 4.40), p = 0.004, and 2.59 (1.35, 4.98), p = 0.004, respectively), although the latter was partly mediated by BMI. In women without GDM, the lowest quartile of B12 and highest quartile of folate had significantly higher adjusted risk of fetal macrosomia (RR 5.3 (1.26, 21.91), p = 0.02 and 4.99 (1.15, 21.62), p = 0.03 respectively). Conclusion: This is the first study from the UK to show that maternal B12 levels are associated with BMI, risk of GDM, and additionally may have an independent effect on macrosomia. Due to the increasing burden of maternal obesity and GDM, longitudinal studies with B12 measurements in early pregnancy are needed to explore this link. PMID:27916927

  2. Killer Treg cells ameliorate inflammatory insulitis in non-obese diabetic mice through local and systemic immunomodulation.

    PubMed

    Kaminitz, Ayelet; Yolcu, Esma S; Mizrahi, Keren; Shirwan, Haval; Askenasy, Nadir

    2013-08-01

    Treg cells endowed with enhanced killing activity through decoration with Fas-ligand (FasL) protein (killer Treg) have been effective in delay of hyperglycemia in prediabetic non-obese diabetic (NOD) mice. In this study, we assessed the therapeutic efficacy of these cells, harvested from age-matched euglycemic NOD donors, on the course of disease in new-onset diabetics. One dose of 4 × 10(6) killer Treg cells stabilized blood glucose associated with increased insulin levels in 5 of 9 mice and partially reversed the severity of islet inflammation, whereas naive Treg cells did not modulate the course of disease significantly. Killer Treg cells were shown to operate through induction of cell apoptosis within the pancreatic lymph nodes, resulting in reduced efficiency of adoptive disease transfer to NOD/SCID recipients. A second mechanism of action consisted of increased fractions of CD4(+)CD25(-)FoxP3(+) T cells in the pancreas and all lymphoid organs. Immunomodulation with FasL rather than Treg cells enhanced the expression of CD25 and FoxP3 in the thymus, suggesting a possible contribution of thymic output to prolonged stabilization of the glucose levels. Autologous Treg cells evolve as excellent vehicles for targeted delivery of FasL as an immunomodulatory protein, which delete pathogenic cells at the site of inflammation and induce systemic dominance of suppressor subsets.

  3. Increased insulin translation from an insulin splice-variant overexpressed in diabetes, obesity, and insulin resistance.

    PubMed

    Minn, Alexandra H; Lan, Hong; Rabaglia, Mary E; Harlan, David M; Peculis, Brenda A; Attie, Alan D; Shalev, Anath

    2005-03-01

    Type 2 diabetes occurs when pancreatic beta-cells become unable to compensate for the underlying insulin resistance. Insulin secretion requires beta-cell insulin stores to be replenished by insulin biosynthesis, which is mainly regulated at the translational level. Such translational regulation often involves the 5'-untranslated region. Recently, we identified a human insulin splice-variant (SPV) altering only the 5'-untranslated region and conferring increased translation efficiency. We now describe a mouse SPV (mSPV) that is found in the cytoplasm and exhibits increased translation efficiency resulting in more normal (prepro)insulin protein per RNA. The RNA stability of mSPV is not increased, but the predicted secondary RNA structure is altered, which may facilitate translation. To determine the role of mSPV in insulin resistance and diabetes, mSPV expression was measured by quantitative real-time RT-PCR in islets from three diabetic and/or insulin-resistant, obese and nonobese, mouse models (BTBRob/ob, C57BL/6ob/ob, and C57BL/6azip). Interestingly, mSPV expression was significantly higher in all diabetic/insulin-resistant mice compared with wild-type littermates and was dramatically induced in primary mouse islets incubated at high glucose. This raises the possibility that the mSPV may represent a compensatory beta-cell mechanism to enhance insulin biosynthesis when insulin requirements are elevated by hyperglycemia/insulin resistance.

  4. Serum Visfatin and Fetuin-A Levels and Glycemic Control in Patients with Obese Type 2 Diabetes Mellitus

    PubMed Central

    Gunduz, Fethiye Oztop; Temizel, Mustafa; Faki, Yilmaz; Cakmak, Mustafa; Durmuscan, Mustafa; Sezgin, Funda

    2011-01-01

    Background Visfatin is an adipokine produced by visceral adipose tissue and has insulin-mimicking effects. Fetuin-A is a hepatic secretory protein that binds the insulin receptor and inhibits insulin action both in vivo and in vitro. The authors of the present study aimed to investigate the levels of serum visfatin and fetuin-A and their correlation with hemoglobin A1c (HbA1c) and urine albumin levels in patients with type 2 diabetes mellitus (T2DM). Methods A total of 40 obese patients with T2DM (11 males and 29 females; age, 54.47±10.83 years and 23 obese nondiabetic controls (8 males and 15 females; age, 53.04±11.33 years) were included in the study. Age, sex, and body ma