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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pubertal transition has been identified as a time of risk for development of type 2 diabetes, particularly among vulnerable groups, such as African Americans (AAs). Documented ethnic differences in insulin secretory dynamics may predispose overweight AA adolescents to risk for type 2 diabetes. The objectives of this longitudinal study were to quantify insulin secretion and clearance in a cohort of 90 AA and European American (EA) children over the pubertal transition and to explore the association of genetic factors and adiposity with repeated measures of insulin secretion and clearance during this critical period. Insulin sensitivity was determined by intravenous glucose tolerance test (IVGTT) and minimal modeling; insulin secretion and clearance by C-peptide modeling; genetic ancestry by admixture analysis. Mixed-model longitudinal analysis indicated that African genetic admixture (AfADM) was independently and positively associated with first-phase insulin secretion within the entire group (P < 0.001), and among lean children (P < 0.01). When examined within pubertal stage, this relationship became significant at Tanner stage 3. Total body fat was a significant determinant of first-phase insulin secretion overall and among obese children (P < 0.001). Total body fat, but not AfADM, was associated with insulin clearance (P < 0.001). In conclusion, genetic factors, as reflected in AfADM, may explain greater first-phase insulin secretion among peripubertal AA vs. EA; however, the influence of genetic factors is superseded by adiposity. The pubertal transition may affect the development of the beta-cell response to glucose in a manner that differs with ethnic/genetic background.
Obesity (Silver Spring) 2009 Jul
PMID:Obesity attenuates the contribution of African admixture to the insulin secretory profile in peripubertal children: a longitudinal analysis. 1919 65

We examined the prospective association of childhood BMI z-score and BMI categories (normal or overweight) with young adult diabetes, controlling for early life, childhood, and adolescence factors. A subsample of 2,639 young adults from the Mater-University study of pregnancy (MUSP) and its outcomes, a prospective birth cohort who were born in Brisbane, Australia and for whom we had measured height and weight at 5 years and self-reported diabetes at age 21 years. The risk of developing diabetes by age 21 years was greater among young adults who had greater BMI z-score or were overweight at age 5 years than those who had normal BMI at age 5 years. Young adults who were overweight at age 5 years had an increased odds ratio of 2.60 (95% confidence interval (CI): 1.29, 5.22, in age- and sex-adjusted model) of experiencing diabetes by age 21 years. Adjustment for potential confounders and mediators including intrauterine environmental factors, childhood dietary patterns, television watching, participation in sports and exercise, and current weight, did not substantively alter these associations. Overweight and increasing BMI z-score at childhood is an independent predictor of young adult's type 1 and type 2 diabetes. Findings of this study suggest that childhood BMI may be central to the development and rising incidence of all diabetes.
Obesity (Silver Spring) 2009 Jun
PMID:Childhood overweight status predicts diabetes at age 21 years: a follow-up study. 1921 72

Measures of obesity, especially central adiposity, have been associated with reduced lung function. However, previous studies may have been affected by confounding by physical activity and fitness. This study aimed to examine the relationship among body fatness, fat distribution, and lung function, adjusted for physical activity energy expenditure (PAEE) and aerobic fitness (VO(2)max), in a cohort of British white adults with a family history of type 2 diabetes. A total of 320 adults (mean age 40.4 +/- 6.0 years) attended for anthropometric and VO(2)max testing, and had ambulatory heart rate monitoring for 4 days to determine PAEE. Spirometry was used to measure forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC). The tests were repeated 12 months later, and a cross-sectional analysis using linear regression with repeated measures was performed. Measures of obesity (BMI, waist circumference (WC), fat mass (FM), body fat percentage (BF%)) were associated with lower lung function in men and women (P < 0.01), while waist-to-hip ratio (WHR) was associated with lower lung function in men only (P < 0.001). Associations remained after adjusting for age, smoking status, height, PAEE, and VO(2)max. The estimated difference in mean FEV(1) and FVC per unit increase in the exposure measures were consistently stronger in men compared to women (P for interaction <0.001). Obesity is inversely associated with lung function in adults, but central fat distribution appears to have a stronger relationship with respiratory mechanics in men than in women. These associations were independent of the degree of physical activity and aerobic fitness in this cohort.
Obesity (Silver Spring) 2009 Mar
PMID:Obesity is associated with altered lung function independently of physical activity and fitness. 1921 60

Serum adiponectin levels have been positively associated with insulin sensitivity and are decreased in type 2 diabetes (T2D) and obesity. Genetic and environmental factors influence serum adiponectin and may contribute to risk of metabolic syndrome and T2D. Therefore, we investigated the effect of ADIPOQ single-nucleotide polymorphisms (SNPs), -11377C>G and -11391G>A, on metabolic-related traits, and their modulation by dietary fat in white Americans. Data were collected from 1,083 subjects participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Mean serum adiponectin concentration was higher for carriers of the -11391A allele (P = 0.001) but lower for the -11377G allele carriers (P = 0.017). Moreover, we found a significant association with obesity traits for the -11391G>A SNP. Carriers of the -11391A allele had significantly lower weight (P = 0.029), BMI (P = 0.019), waist (P = 0.003), and hip circumferences (P = 0.004) compared to noncarriers. Interestingly, the associations of the -11391G>A with BMI and obesity risk were modified by monounsaturated fatty acids (MUFAs) intake (P-interaction = 0.021 and 0.034 for BMI and obesity risk, respectively). In subjects with MUFA intake above the median (> or =13% of energy intake), -11391A carriers had lower BMI (27.1 kg/m(2) for GA+AA vs. 29.1 kg/m(2) for GG, P = 0.002) and decreased obesity risk (odds ratio for -11391A = 0.52, 95% confidence interval (CI); 0.28-0.96; P = 0.031). However, we did not detect genotype-related differences for BMI or obesity in subjects with MUFA intake <13%. Our findings support a significant association between the -11391G>A SNPs and obesity-related traits and the potential to moderate such effects using dietary modification.
Obesity (Silver Spring) 2009 Mar
PMID:ADIPOQ polymorphisms, monounsaturated fatty acids, and obesity risk: the GOLDN study. 1923 39

We determined serum adiponectin's role as a biomarker of metabolic syndrome (MetS), type 2 diabetes (DM) and hypertension among Turkish adults who have a high prevalence of MetS. Individuals with measured serum adiponectin concentrations, constituting a random sample of Turkish adults, were studied cross-sectionally. MetS was identified by criteria of the Adult Treatment Panel-III modified for male abdominal obesity. Median age of 547 men and 652 women was 54 years. MetS was identified in 46%. Linear regression analysis among nine variables revealed homeostatic model assessment (HOMA) index in both sexes and C-reactive protein (CRP) only in men as inversely associated covariates of adiponectin, and sex hormone-binding globulin (SHBG) as positive covariate in women. Age-adjusted sex-specifically dichotomized high vs. low adiponectin levels were significantly associated with DM (odds ratio (OR) 0.55, P = 0.01) and hypertension (OR 0.64, P = 0.012) in women, but not in men. Further adjustment for smoking status and presence of high/low BMI did not alter this sex-based relationship. As regards association with MetS, low adiponectin and high BMI interacted significantly in each sex. Yet adiponectin was associated only in men additively to the simultaneously adjusted five MetS components. We conclude that adiponectin concentrations, clearly linked to metabolic disorders, may diverge among sexes regarding protection against cardiometabolic risk through anti-inflammatory or antioxidative function, Turkish men alone revealing significant dysfunction independent of obesity. This dysfunction may underlie also the association of adiponectin levels with MetS in men to be independent of the MetS components.
Obesity (Silver Spring) 2009 Mar
PMID:Serum adiponectin confers little protection against diabetes and hypertension in Turkish men. 1923 42

With the emerging obesity pandemic, identifying those who appear to be protected from adverse consequences such as type 2 diabetes and certain malignancies will become important. We propose that the circulating immune system plays a role in the development of these comorbidities. Clinical data and blood samples were collected from 52 patients with severe obesity attending a hospital weight-management clinic and 11 lean healthy controls. Patients were classified into metabolically "healthy obese" (n = 26; mean age 42.6 years, mean BMI 46.8 kg/m(2)) or "unhealthy obese" (n = 26; mean age 45 years, mean BMI 47.5 kg/m(2)) groups, based upon standard cutoff points for blood pressure, lipid profile, and fasting glucose. Circulating lymphoid populations and phenotypes were assessed by flow cytometry. Obese patients had significantly less circulating natural killer (NK) and cytotoxic T lymphocytes (CTL) compared to lean controls. There were significantly higher levels of NK cells and CTLs in the healthy obese group compared to the unhealthy obese group (NK: 11.7% vs. 6.5%, P < 0.0001, CD8 13.4% vs. 9.3%, P = 0.04), independent of age and BMI and these NK cells were also less activated in the healthy compared to the unhealthy group (CD69, 4.1% vs. 11.8%, P = 0.03). This is the first time that quantitative differences in the circulating immune system of obese patients with similar BMI but different metabolic profiles have been described. The significantly higher levels of CTLs and NK cells, which express fewer inhibitory molecules, could protect against malignancy, infection, and metabolic disease seen in obesity.
Obesity (Silver Spring) 2009 Mar
PMID:Are natural killer cells protecting the metabolically healthy obese patient? 1923 45

Adrenomedullin (ADM) is a vasoactive peptide found to be related to obesity and its comorbidities: type 2 diabetes, hypertension, atherosclerosis, and coronary heart disease. ADM is increased both in plasma and in adipose tissue of obese individuals when compared to lean subjects and is considered as a member of the adipokine family. We determined plasma midregional proadrenomedullin (MR-proADM) concentrations in a cohort of 357 subjects with BMI ranging from 17.5 to 42.3 kg/m2 and no additional medical history. In parallel, 28 severely obese patients scheduled to undergo laparoscopic Roux-en-Y gastric bypass (RYGB) surgery were studied at two time points: before and 1 year after surgery. Outcome measurements were: MR-proADM, cortisol, leptin, C-reactive protein (CRP) thyroid-stimulating hormone (TSH), creatinine and metabolic parameters. BMI correlated significantly to plasma MR-proADM levels (r=0.714, P<0.001), also after adjustment for age and gender (r=0.767, P<0.001). In obese subjects, there was a positive relationship between MR-proADM and leptin (r=0.511, P=0.006). Following RYGB, plasma MR-proADM decreased from 0.76+/-0.03 to 0.62+/-0.02 pg/ml (P<0.0001). RYGB-induced changes in MR-proADM correlated significantly to changes in leptin (r=0.533, P=0.004) and in CRP (r=0.429, P=0.023). We conclude that BMI is an independent predictor of circulating MR-proADM levels. Weight loss after RYGB is associated with a significant decrease in plasma MR-proADM, which is related to surgery-induced changes in both circulating leptin and systemic inflammation.
Obesity (Silver Spring) 2009 Jun
PMID:Plasma MR-proADM correlates to BMI and decreases in relation to leptin after gastric bypass surgery. 1924 78

Few randomized trials attempt to improve insulin sensitivity and associated metabolic risks in overweight Latino youth. The purpose of this study is to examine the effects of a modified carbohydrate nutrition program combined with strength training on insulin sensitivity, adiposity, and other type 2 diabetes risk factors in overweight Latino adolescents. In a 16-week randomized trial, 54 overweight Latino adolescents (15.5 +/- 1.0 years) were randomly assigned to: (i) Control (C; n = 16), (ii) Nutrition (N; n = 21), or (iii) Nutrition + Strength training (N+ST; n = 17). The N group received modified carbohydrate nutrition classes (once per week), while the N+ST received the same nutrition classes plus strength training (twice per week). The following were measured at pre- and postintervention: strength by 1-repetition maximum, dietary intake by 3-day records, body composition by dual-energy X-ray absorptiometry, glucose/insulin indices by oral glucose tolerance test (OGTT) and intravenous glucose tolerance test with minimal modeling. Across intervention group effects were tested using analysis of covariance with post hoc pairwise comparisons. A significant overall intervention effect was found for improvement in bench press (P < 0.001) and reductions in energy (P = 0.05), carbohydrate (P = 0.04) and fat intake (P = 0.03). There were no significant intervention effects on insulin sensitivity, body composition, or most glucose/insulin indices with the exception of glucose incremental area under the curve (IAUC) (P = 0.05), which decreased in the N and N+ST group by 18 and 6.3% compared to a 32% increase in the C group. In conclusion, this intense, culturally tailored intervention resulted in no significant intervention effects on measured risk factors with the exception of a beneficial effect on glycemic response to oral glucose.
Obesity (Silver Spring) 2009 Aug
PMID:Randomized control trial to improve adiposity and insulin resistance in overweight Latino adolescents. 1924 80

Body fat distribution modulates risk for type 2 diabetes mellitus. We evaluated potentially involved metabolic risk factors. In a population of 282 male and 157 female healthy subjects (data from the San Antonio and the European Group of Insulin Resistance (EGIR) study cohorts), we evaluated associations between body fat distribution (assessed by waist and hip circumference) and parameters of lipid- and glucose metabolism, including clamp measurements of insulin sensitivity. After stratification for BMI, fasting triglycerides were lower in the presence of a large hip, and higher in a large waist. Persons with the largest BMI (3rd tertile) showed a difference in triglyceride levels of 1.5 vs. 2.4 mmol/l in large vs. small hip circumference groups (P < 0.038), and a difference of 1.5 vs. 1.2 mmol/l in large vs. small waist circumference groups (P < 0.025). A similar analysis did not reveal a difference in insulin sensitivity. Linear regression analyses confirmed the findings; they revealed negative associations between triglycerides and hip, and (for women borderline statistically significant) positive associations between triglycerides and waist, after adjustment for BMI, mutual confounding, and age (beta +/- s.e.; men: -0.48 +/- 0.005, P < 0.001, and 0.21 +/- 0.005, P < 0.05; women: -0.78 +/- 0.007, P < 0.001, and 0.24 +/- 0.005, P < 0.065), respectively. Linear regression analyses revealed similar opposite associations with high-density lipoprotein (HDL)-cholesterol, though not with glucose, insulin, or insulin sensitivity as measured with the clamp method. In our study population of healthy persons, body fat distribution is associated with fasting triglycerides and HDL-cholesterol, and not with insulin sensitivity. Metabolic risk of unfavorable body fat distribution may be modulated by lower triglyceride storage capacity.
Obesity (Silver Spring) 2009 Aug
PMID:Low fasting triglycerides: hallmark of the healthy large hip? 1924 83

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance. It is also a predisposing factor for type 2 diabetes. Dietary factors are believed to contribute to all three diseases. NAFLD is characterized by increased intrahepatic fat and mitochondrial dysfunction, and its etiology may be attributed to excessive fructose intake. Consumption of high fructose corn syrup-55 (HFCS-55) stands at up to 15% of the average total daily energy intake in the United States, and is linked to weight gain and obesity. The aim of this study was to establish whether HFCS-55 could contribute to the pathogenesis of NAFLD, by examining the effects of HFCS-55 on hepatocyte lipogenesis, insulin signaling, and cellular function, in vitro and in vivo. Exposure of hepatocytes to HFCS-55 caused a significant increase in hepatocellular triglyceride (TG) and lipogenic proteins. Basal production of reactive oxygen metabolite (ROM) was increased, together with a decreased capacity to respond to an oxidative challenge. HFCS-55 induced a downregulation of the insulin signaling pathway, as indicated by attenuated (ser473)phosphorylation of AKT1. The c-Jun amino-terminal kinase (JNK), which is intimately linked to insulin resistance, was also activated; and this was accompanied by an increase in endoplasmic reticulum (ER) stress and intracellular free calcium perturbation. Hepatocytes exposed to HFCS-55 exhibited mitochondrial dysfunction and released cytochrome C (CytC) into the cytosol. Hepatic steatosis and mitochondrial disruption was induced in vivo by a diet enriched with 20% HFCS 55; accompanied by hypoadiponectinemia and elevated fasting serum insulin and retinol-binding protein-4 (RBP4) levels. Taken together our findings indicate a potential mechanism by which HFCS-55 may contribute to the pathogenesis of NAFLD.
Obesity (Silver Spring) 2009 Nov
PMID:Diabetes of the liver: the link between nonalcoholic fatty liver disease and HFCS-55. 1928 20


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