Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was to assess whether the baseline risk of psychiatric and cardiovascular disease in patients with diabetes mellitus differs between those starting to use antiobesity drugs and those not starting to use these drugs. A retrospective nested case-control study within the General Practice Research Database (1987-2002) was done. The cohort included all patients with diabetes mellitus (n = 141,164). Information on patient characteristics (general, cardiovascular, and psychiatric characteristics) was extracted from the medical records. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A total of 511 patients starting to use antiobesity drugs (cases) and 3,065 controls were included in the study cohort. Starters were younger and more frequently female. Of the starters, 91.8% did not receive any dietary advice before starting treatment. Depression (in the year before index date) was associated with the use of antiobesity drugs (OR 2.2; 95% CI 1.7-2.8), as was anxiety (OR 1.6; 95% CI 1.1-2.4). Of the cases, 25.2% had multiple cardiovascular risk factors (>4) compared to 19.0% of the controls. The baseline risk for psychiatric disorders and cardiovascular disease was found to be higher in patients with diabetes mellitus starting to use antiobesity drugs compared to patients with diabetes mellitus not starting such treatment.
Obesity (Silver Spring) 2008 Oct
PMID:Psychiatric and cardiovascular comorbidities in patients with diabetes mellitus starting antiobesity drugs. 1871 29

Phenotypic heterogeneity complicates detection of genomic loci predisposing to type 2 diabetes, potentially obscuring or unmasking specific loci. We conducted ordered-subsets linkage analyses (OSAs) for diabetes-related quantitative traits (fasting insulin and glucose, hemoglobin A1c (HbA1c), and 28-year-time-averaged fasting plasma glucose (FPG)) from 330 families of the Framingham Offspring Study. We calculated mean BMI, waist circumference (WC), and a diabetes "age-of-onset score" for each family. We constructed subsets by adding one family at a time in increasing (lean family to obese) or decreasing (obese to lean) adiposity order, or increasing or decreasing propensity to develop diabetes at a younger age, with the OSA LOD reported as the maximum LOD observed in any subset. Permutation P values tested the hypothesis that phenotypic ordering showed stronger linkage than random ordering. On chromosome 1, ordering by increasing family mean WC increased linkage to time-averaged FPG at 256 cM from LOD = 2.4 to 3.5 (permuted P = 0.02) and to HbA1c at 180 cM from LOD = 2.0 to 3.3 (P = 0.01). On chromosome 19, ordering by decreasing WC increased linkage to fasting insulin at 68 cM from LOD = 2.7 to 4.6 (P = 0.002), and ordering by decreasing propensity to develop diabetes at a young age increased linkage to fasting insulin at 73 cM from LOD = 2.7 to 4.0 (P = 0.046). We conclude that chromosomes 1 and 19 could harbor adiposity-interacting diabetes susceptibility genes. Such interactions might also influence trait-locus associations and may be useful to consider in diabetes genome-wide association studies.
Obesity (Silver Spring) 2008 Oct
PMID:Ordered stratification to reduce heterogeneity in linkage to diabetes-related quantitative traits. 1871 43

Retinol-binding protein 4 (RBP-4) has been reported to be associated with visceral-fat accumulation and parameters of the metabolic syndrome (MetS). In this study, we investigated the relationship between RBP-4, visceral fat, and the MetS during pronounced weight loss after bariatric surgery. Thirty-six subjects were examined before and 2 years after surgery. Abdominal-fat distribution was determined by ultrasound, metabolic parameters, and serum RBP-4 levels by standard methods. After surgery BMI decreased by 9.07 kg/m(2), visceral-fat diameter (VFD) decreased by 60.6%, and RBP-4 serum levels by 16.6%. Change of RBP-4 levels was associated with reductions of waist (r = 0.364, P = 0.037), waist-to-hip ratio (WHR) (r = 0.415, P = 0.016), and VFD (r = 0.425, P = 0.010). MetS, as defined by International Diabetes Federation (IDF), was present in 19 patients at baseline and in nine patients at follow-up. Change in RBP-4 levels was the best predictor for the diagnosis of MetS at follow-up. In the subgroup without MetS at baseline, the decrease in RBP-4 levels (-28.1% vs. -6.3%, P = 0.020) and reduction in VFD (-66.9% vs. -55.0%, P = 0.038) were significantly greater compared to the subgroup with MetS. We demonstrate a marked decrease of RBP-4 levels after bariatric surgery, which correlates with reduction in visceral-fat mass. Furthermore, the extent of changes in RBP-4 levels differs according to the severity of the MetS.
Obesity (Silver Spring) 2008 Nov
PMID:Retinol-binding protein 4, visceral fat, and the metabolic syndrome: effects of weight loss. 1871 70

The FTO gene was recently identified as a susceptibility locus for both obesity and type 2 diabetes by whole-genome association analyses of several European populations. We tested for an association between FTO risk alleles and obesity and diabetes in a well-characterized multiethnic cohort of postmenopausal women in the United States. We genotyped two most significantly associated single-nucleotide polymorphisms (SNPs) (rs9939609 and rs8050136) in intron 1 of FTO gene in a nested case-control study of 1,517 diabetes cases and 2,123 controls from the Women's Health Initiative-Observational Study (WHI-OS). The allelic frequencies of either rs9939609 or rs8050136 differed widely across four ethnic groups. The frequency of the rare allele A of rs9939609 among controls was much lower in Asians/Pacific Islanders (17%) than in blacks (45%), whites (40%), and Hispanics (31%). We found significant associations of rs9939609 with BMI and waist circumference in white and Hispanic women, but not among black and Asian/Pacific Islander women. On average, each copy of the risk-allele A at rs9939609 was significantly associated with 0.45 kg/m(2) increase in BMI (95% confidence interval (CI): 0.16-0.74; P = 0.004) and 0.97 cm increase in waist circumference (95% CI: 0.21-0.65; P = 0.0002). Similar results were observed for rs8050136. However, we found no significant genetic associations with diabetes risk, either within the full study sample or in any ethnic group. In conclusion, common genetic variants in the intron 1 of FTO gene may confer a modest susceptibility to obesity in an ethnicity-specific manner, but may be unlikely to contribute to a clinically significant diabetes risk.
Obesity (Silver Spring) 2008 Nov
PMID:FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women. 1878 25

Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol that results in the development of fibrotic cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3 days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in the cardiac extracts of DIO mice were significantly elevated, reflecting primarily the dietary fatty acid (FA) composition. Compared with lean controls, cardiac FA oxidation (FAO) capacity of DIO mice was significantly higher, concurrent with increased expression of FA metabolism gene transcripts. Following 15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased susceptibility to I/R and, in contrast to lean mice, developed microinfarction, which was associated with an exaggerated inflammatory response. Repetitive I/R in DIO mice was associated with more profound significant downregulation of FA metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive metabolic changes of FA metabolism contribute to enhanced myocardial injury in diet-induced obesity.
Obesity (Silver Spring) 2008 Dec
PMID:Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity. 1883 12

The aim of this study was to examine the association between glycemia and markers of early atherosclerosis in healthy nondiabetic individuals. In 309 individuals without diabetes or symptomatic cardiovascular disease, we assessed long-term glycemia by glycosylated hemoglobin (HbA1c) and endothelial function by flow-mediated dilatation (FMD) in the brachial artery. HbA1c was negatively associated with FMD (r = -0.162, P = 0.004). Multivariate linear regression analysis after adjusting for common risk factors of cardiovascular disease showed that BMI was an effect modifier of the association between HbA1c and FMD (P = 0.034 for the HbA1c x BMI interaction). We stratified the FMD outcome data into two groups separated by the median BMI (group 1: BMI < or = 26.1 kg/m(2) and group 2: BMI > 26.1 kg/m(2)). In the lower BMI group, HbA1c was an independent predictor of FMD even when adjusted for confounding factors associated with impaired glucose metabolism (r = -0.215, P = 0.009), but in the higher BMI group HbA1c was not associated with FMD (r = -0.051, P = 0.5). In a nondiabetic population, long-term glycemia was associated with endothelial dysfunction only in lean individuals. In the overweight individuals, this association was not apparent, possibly because some of the mechanisms that mediate the effect of glycemia on vascular function are shared by obesity.
Obesity (Silver Spring) 2008 Dec
PMID:The association between glycemia and endothelial function in nondiabetic individuals: the importance of body weight. 1884 51

For a given level of adiposity, greater lower body circumferences appear to exert a protective effect on several disease outcomes including cardiovascular disease and diabetes; however, the independent associations between extremity circumferences and mortality have not been widely investigated. The purpose of this study was to determine the independent and shared influences of upper- and lower-body circumferences on the risk of mortality in a population-based sample of adults. The sample included 10,638 adults 20-69 years of age (5,012 men; 5,626 women) from the nationally representative 1981 Canada Fitness Survey (CFS), who were monitored for over 12 years for mortality. BMI was calculated from measured height and weight. Waist, hip, thigh, calf, and upper arm circumferences were measured using a flexible, nonelastic anthropometric tape. Sex-specific proportional hazards regression models were used to evaluate the relationship between standardized values (Z-scores) of extremity circumference measures, waist circumference (WC) and mortality. Age, smoking status, alcohol consumption, and leisure-time physical activity were collected by questionnaire and were included as covariates. During 131,563 person-years of follow-up, there were 340 deaths in men and 231 in women. After mutual adjustment, WC was positively associated with mortality whereas arm, thigh, and calf circumferences were significantly protective in men, and arm and thigh circumferences were protective in women. In conclusion, waist and extremity circumferences appear to have opposite, independent effects on mortality in this sample of Canadians. Independent of BMI and WC, men and women with larger extremity circumferences had a lower risk of mortality.
Obesity (Silver Spring) 2008 Dec
PMID:Influence of central and extremity circumferences on all-cause mortality in men and women. 1892 48

Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders including diabetes, hypertension, and heart disease. It is generally accepted that the regulation of adipogenesis or adipokines expression prevents obesity. In this study, we show that isorhamnetin inhibits adipocyte differentiation, as evidenced by reduced triglyceride (TG) accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity. At the molecular level, the mRNA expression levels of peroxidase proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), which are the major adipogenic transcription factors, were markedly reduced by isorhamnetin. However, the mRNA levels of C/EBP-beta and -delta, the upstream regulators of PPAR-gamma and C/EBP-alpha, were not reduced by isorhamnetin. Moreover, the mRNA levels of PPAR-gamma target genes such as lipoprotein lipase (LPL), CD36, aP2, and liver X receptor-alpha (LXR-alpha) were downregulated by isorhamnetin. We also showed that isorhamnetin inhibits the expression and secretion of adiponectin, and the results of adiponectin promoter assays suggest the inhibition of PPAR-gamma expression as a possible mechanism underlying the isorhamnetin-mediated effects. Taken together, these results indicate that isorhamnetin inhibits adipogenesis through downregulation of PPAR-gamma and C/EBP-alpha.
Obesity (Silver Spring) 2009 Feb
PMID:Isorhamnetin represses adipogenesis in 3T3-L1 cells. 1894 72

Despite its overall excellent outcomes, weight loss after Roux-en-Y gastric bypass (RYGB) is highly variable. We conducted this study to identify clinical predictors of weight loss after RYGB. We reviewed charts from 300 consecutive patients who underwent RYGB from August 1999 to November 2002. Data collected included patient demographics, medical comorbidities, and diet history. Of the 20 variables selected for univariate analysis, 9 with univariate P values <or= 0.15 were entered into a multivariable regression analysis. Using backward selection, covariates with P < 0.05 were retained. Potential confounders were added back into the model and assessed for effect on all model variables. Complete records were available for 246 of the 300 patients (82%). The patient characteristics were 75% female, 93% white, mean age of 45 years, and mean initial BMI of 52.3 kg/m(2). One year after surgery, patients lost an average of 64.8% of their excess weight (s.d. = 20.5%). The multivariable regression analysis revealed that limited physical activity, higher initial BMI, lower educational level, diabetes, and decreased attendance at postoperative appointments had an adverse effect on weight loss after RYGB. A model including these five factors accounts for 41% of the observed variability in weight loss (adjusted r(2) = 0.41). In this cohort, higher initial BMI and limited physical activity were the strongest predictors of decreased excess weight loss following RYGB. Limited physical activity may be particularly important because it represents an opportunity for potentially meaningful pre- and postsurgical intervention to maximize weight loss following RYGB.
Obesity (Silver Spring) 2009 Jan
PMID:Capacity for physical activity predicts weight loss after Roux-en-Y gastric bypass. 1899 74

The aim of the study was to compare BMI with waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-stature ratio (WSR) as a predictor of diabetes incidence. A total of 1,841 men and 2,104 women of Mauritian Indian and Mauritian Creole ethnicity, aged 25-74 years, free of diabetes, hypertension, cardiovascular disease, and gout were seen at baseline in 1987 or 1992, and follow-up in 1992 and/or 1998. At all time points, participants underwent a 2 h 75 g oral glucose tolerance test. Hazard ratios for diabetes incidence were estimated applying an interval-censored survival analysis using age as timescale. Six hundred and twenty-eight individuals developed diabetes during the follow-up period. Multivariable adjusted hazard ratios for diabetes incidence corresponding to a 1 s.d. increase in baseline BMI, WC, WHR, and WSR for Mauritian Indians were 1.49 (1.31-1.71), 1.58 (1.38-1.81), 1.54 (1.37-1.72), and 1.61 (1.41-1.84) in men and 1.33 (1.17-1.51), 1.35 (1.19-1.53), 1.39 (1.24-1.55), and 1.38 (1.21-1.57) in women, respectively; and for Mauritian Creoles they were 1.86 (1.51-2.30), 2.07 (1.68-2.56), 1.92 (1.62-2.26), and 2.17 (1.76-2.69) in men and 1.29 (1.06-1.55), 1.27 (1.04-1.55), 1.24 (1.04-1.48), and 1.27 (1.04-1.55) in women. Paired homogeneity tests showed that there was no difference between BMI and each of the central obesity indicators (all P > 0.05). The relation of BMI with the development of diabetes was as strong as that for indicators of central obesity in this study population.
Obesity (Silver Spring) 2009 Feb
PMID:BMI compared with central obesity indicators as a predictor of diabetes incidence in Mauritius. 1900 66


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