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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Zucker diabetic fatty (ZDF) rat is a commonly used animal model of type 2 diabetes yet complete descriptions of insulin resistance in this model are limited. We present a full characterisation of in vivo insulin resistance in obese (fa/fa) animals compared to lean (+/?) littermates. Anaesthetised, ten-week old, obese ZDF rats and their lean littermates underwent a hyperinsulinaemic euglycaemic glucose clamp. Compared with lean littermates, obese ZDF rats required an 89% lower glucose infusion rate to maintain euglycaemia and showed a 35% decrease in peripheral glucose disposal. Insulin-stimulated glucose uptake (R(g')) in obese animals was also significantly less in all skeletal muscles studied. R(g') in cardiac and white adipose tissue was not different between the two groups. Total glycogen content in skeletal and cardiac muscle was significantly less in obese animals, while total glycogen content in the liver was significantly greater than in lean littermates. Glycogen synthesis was also decreased in skeletal muscle of obese animals. Compared with lean animals, total triglyceride content was significantly greater in skeletal muscle, heart and liver of obese ZDF rats. Obese animals also showed significantly increased glucose incorporation into lipid in all of these tissues, indicating an increase in lipogenesis. Collectively, these results provide an integrated characterisation of in vivo insulin resistance in obese ZDF rats and a direct comparison with lean littermates.
Acta Diabetol 2005 Dec
PMID:Insulin resistance in the Zucker diabetic fatty rat: a metabolic characterisation of obese and lean phenotypes. 1638 3

The epidemic of obesity concerns also children and adolescents. Excess weight increases the risk of metabolic complications, diabetes type 2, hypertension, cardiovascular disease, pulmonary and musculoskeletal disorders, psychosocial problems. Simple obesity leads to secondary endocrine disturbances. Long lasting insulin resistance and proinflammatory state induced by cytokines, which are produced in adipose tissue, play the main role in the development of obesity associated complications. Many disturbances can be reversed at the early stage, if even small weight loss is achieved.
Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw 2006
PMID:[Obesity related complications in children and adolescents]. 1702 Jun 60

Obstructive sleep apnoea (OSA) is a cardio-metabolic disorder. Whether metabolic syndrome (MS), insulin resistance (IR) and albuminuria are independently associated with OSA is unclear, but defining the interactions between OSA and various cardiovascular (CV) risk factors independent of obesity facilitates the development of therapeutic strategies to mitigate their increased CV risks. We prospectively recruited 38 subjects with OSA and 41 controls. Anthropometric measurements, glucose, lipids, insulin and blood pressure (BP) were measured after an overnight fast. IR state was defined as homeostasis model assessment (HOMA) value >3.99 and MS diagnosed according to the International Diabetes Federation (IDF) criteria. Subjects with OSA were more obese, more insulin resistant, more hyperglycaemic, had higher Epworth score (measure of day time somnolence) and systolic blood pressure levels. The prevalence of MS was higher in OSA compared with non-OSA subjects (74% vs 24%, p < 0.001). The prevalence of microalbuminuria in both groups was negligible. Logistic regression adjusted for age, BMI and smoking showed that the patient with OSA was 5.9 (95% CI 2.0-17.6) times more likely to have MS than non-OSA patient. Triglyceride (p = 0.031), glucose (0.023) and Epworth score (0.003) values were independently associated with OSA after adjusting for BMI and other covariates whilst IR status was found not to be significant. Using the ROC curve analysis, we found that a waist circumference of >103 cm would predict MS in patients with OSA at 75-78% sensitivity and 61-64% specificity. The agreement between MS and IR state in this cohort is poor. Thus, OSA is associated with MS independent of obesity predominantly due to increased triglyceride, glucose and Epworth score values but not IR or microalbuminuria status. This observation suggests an alternative pathogenic factor mediating the increased cardiovascular risk in patients with OSA and MS, other than that due to IR. The independent link between Epworth score and MS in patients with OSA implicates the role of daytime sleepiness and chronic hypoxia as a potential mediator. Given the discordant between MS and IR state, measurement of waist is useful for predicting mainly MS but not insulin resistance status in patients with OSA. Appropriate pharmacological intervention targeting these independent factors is important in reducing the increased CV risks among patients with OSA.
Cardiovasc Diabetol 2006 Nov 01
PMID:Obstructive sleep apnoea is independently associated with the metabolic syndrome but not insulin resistance state. 1707 84

The aim of this study was to assess the frequency of fatty acid binding protein 2 (FABP2) Ala54Thr genetic polymorphism and to evaluate its association with obesity and insulin resistance in Chilean aboriginal populations. A sample of 96 urban Aymara and 111 urban Mapuche subjects aged 20-80 years were recruited for this cross-sectional study. Glucose, insulin and lipid profile were measured in fasting plasma samples. Insulin resistance was estimated through the HOMA-IR model. FABP2 Ala54Thr genotypes were determined by PCR followed by RFLP analysis. The allele frequency of Thr54 variant was estimated as 18.2% in Aymara subjects, which is one of the lowest reported to date. The corresponding frequency in Mapuche subjects was 31.9% (p<0.002). Regarding genotype-phenotype associations, no significant differences were found in any of the anthropometric or metabolic variables according to Ala54Thr genotypes. After adjustment by BMI and metabolic variables through a logistic regression analysis, the association of the FABP2 polymorphism with ethnic group persisted (Mapuche group: OR=2.37, 95% CI 1.319-4.277, p=0.004) It is unlikely that Ala54Thr polymorphism of the FABP2 gene plays a relevant role in obesity and insulin resistance in Chilean ethnic groups.
Acta Diabetol 2006 Dec
PMID:Lack of association between the fatty acid binding protein 2 (FABP2) polymorphism with obesity and insulin resistance in two aboriginal populations from Chile. 1721 57

Currently there is a surge of interest in the association of obesity with growth hormone (GH). Our hypothesis is that genetic variation within the hGH area could predispose to obesity in type 2 diabetes. We examined 68 Caucasian subjects with type 2 diabetes from the central area of Continental Italy. In these subjects we examined four polymorphic loci (Msp1A, Msp1B, BglIIA and BglIIB) located in the hGH gene region (chromosome 17q22-9-24). A sample of 192 adults from the population of Central Italy were studied as controls. Msp1B and Msp1A polymorphisms are associated with BMI. For both polymorphisms the proportion of overweight subjects is greater in the *1/*1 genotype than in carriers of the *2 allele (97% vs. 79% and 94% vs. 86% respectively). For both polymorphisms, the mean value of BMI is greater in the *1/*1 genotype than in carriers of the *2 allele. The mean values of age at onset of diabetes are greater in Msp1B*1/*1 and Msp1A*1/*1 genotypes than in carriers of the *2 allele. BglIIA and BglIIB polymorphisms are not associated with being overweight. The present study suggests that the structural organisation of the hGH genomic area may have an important role in being overweight associated with type 2 diabetes.
Acta Diabetol 2006 Dec
PMID:Genetic polymorphism within human growth hormone gene region and BMI in type 2 diabetes. 1721 58

Evidence exists that some clinical, metabolic and genetic risk factors are associated with the development of diabetic retinopathy (DR). The aim of the study was: (1) to define the prevalence of DR in the examined group of 267 patients with type 2 diabetes mellitus (T2DM) from a Polish population; (2) to identify in cross-sectional analysis, the clinical features associated with DR in the study group; and (3) to search for the association of 4 markers of vitamin D receptor (VDR), a candidate gene for vascular complications in diabetes, with DR. The examined group consisted of 146 female and 121 male T2DM patients (mean age at examination: 61.3+/-9.4 years; age at T2DM diagnosis: 50.0+/-9.2; T2DM duration: 11.3+/-7.8 years; body mass index (BMI): 30.5+/-5.5 kg/m(2); HbA1c: 7.8+/-1.5%). In all patients, the clinical and metabolic profile was determined. Diagnosis of DR was determined by a trained ophthalmologist by ophthalmoscopy after pupillary dilatation. Colour photographic documentation was made. The examined T2DM patients were genotyped for FokI, ApaI, BsmI and TaqI frequent VDR polymorphisms based on the restriction fragment length polymorphism method. The statistical analysis was performed using univariate and multivariate logistic regression (SAS) and haplotype analysis (Haplostat). DR was detected in 85 (31.8%) patients with T2DM. The multivariate analysis revealed that significant predictors of this complication were: never-smoking status (odds ratio 2.2, 95% confidence interval 1.2-4), urea serum level (1.3, 1.1-1.5), HbA1c level (1.4, 1.1-1.8) and insulin treatment (2.7, 1.4-5.1). Other features such as age of T2DM diagnosis, T2DM duration prior to ophthalmic exam, obesity (BMI>30), serum creatinine level, albumin/creatinine ratio and arterial hypertension were univariate predictors of DR, however they lost significance as independent predictors in multivariate analysis. Similarly, the alleles, genotypes, haplotype and haplotype combination of VDR were not associated with the examined complication. However, there was a suggestion of a possible slight association between the fbaT haplotype and DR (p=0.11). In conclusion, our study showed that DR in T2DM patients remains a frequent complication in Polish T2DM patients. We were able to confirm the role of some clinical risk factors, surprisingly including not-smoking status, as was previously shown in the UK Prospective Diabetes Study (UKPDS). VDR gene polymorphisms did not constitute a risk factor for this size of study group.
Acta Diabetol 2006 Dec
PMID:Clinical risk factors and the role of VDR gene polymorphisms in diabetic retinopathy in Polish type 2 diabetes patients. 1721 61

The KK/Ta strain serves as a suitable polygenic mouse model for type 2 diabetes associated with fasting hyperglycaemia, glucose intolerance, hyperinsulinaemia, mild obesity and dyslipidaemia. Recently, we reported the susceptibility loci contributing to type 2 diabetes and related phenotypes in KK/Ta mice. In the present study, to identify susceptibility genes for type 2 diabetes and related disorders, GeneChip Expression Analysis was employed to survey the gene expression profile in the liver of KK/Ta and BALB/c mice. M-cadherin, a calciumdependent intercellular adhesion molecule, showed increased expression in the liver of KK/Ta mice, and sequence analysis revealed three missense mutations. The relationship between these polymorphisms and various phenotypes in 208 KK/Ta x (BALB/c x KK/Ta) F1 backcross mice was analysed. Statistical analysis revealed that M-cadherin exhibits linkage to levels of triglyceride and insulin in sera, glucose tolerance and body weight. Although it has been postulated that M-cadherin may be important for the regulation of morphogenesis of skeletal muscle cells, these results suggest that M-cadherin may influence hypertriglyceridaemia, glucose intolerance, hyperinsulinaemia and obesity in KK/Ta mice.
Acta Diabetol 2007 Mar
PMID:M-cadherin, a candidate gene for type 2 diabetes and related phenotypes in a KK/Ta mouse model. 1735 79

Pancreatic beta-cell dysfunction is an important pathological change in type 2 diabetes, which is tightly related to obesity. However, the direct role of adipose tissue in beta-cell dysfunction has not been well understood. In this study, we examined the effects of 3T3-L1 adipocytes on MIN6 insulin-secreting cells in a co-culture system. MIN6 cells used here kept most of beta-cell functions but less sensitive to glucose stimulation. Tolbutamide, the KATP channel blocker, was therefore used to stimulate insulin secretion in this report. MIN6 cells co-cultured with 3T3-L1 adipocytes had significantly reduced intracellular calcium concentration ([Ca2+]i) and lost the ability to secrete insulin in response to tolbutamide, compared to the control cells. 3T3-L1 adipocytes significantly decreased the expression of insulin, glucokinase and Kir6.2 genes but increased the expression of uncoupling protein-2 (UCP-2) in MIN6 cells after one week of co-culture, as measured by semi-quantitative RT-PCR. 3T3-L1 adipocyte-conditioned medium also significantly decreased insulin secretion and the expression of insulin, glucokinase and Kir6.2 genes in MIN6 cells. The conditioned medium also reduced tyrosine kinase activity in MIN6 cells. The inhibitor of protein tyrosine kinase, genistein, decreased the expression of glucokinase and Kir6.2 in MIN6 cells, while two free fatty acids, oleic acid and linoleic acids, were found to increase UCP-2 expression. The present study demonstrates that 3T3-L1 adipocytes directly impair insulin secretion and the expression of important genes in MIN6 cells. The effects of T3-L1 adipocytes on MIN6 cells are ascribed to secreted bioactive factors and may be mediated via multiple pathways, which include the upregulation of UCP-2 expression via free fatty acids, and downregulation of glucokinase and Kir6.2 expression via decreasing protein tyrosine kinase activity.
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PMID:3T3-L1 adipocytes induce dysfunction of MIN6 insulin-secreting cells via multiple pathways mediated by secretory factors in a co-culture system. 1770 98

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Paucity of data on maternal-foetal status of essential trace elements in obese diabetic pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous blood samples were collected from obese gestational diabetic patients (Body Mass Index (BMI) >30) and control obese pregnant women (BMI>30) at time of spontaneous delivery or caesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se and Zn were determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant (TAO) in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-foetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se and Zn in serum of control obese pregnant women (n=10) averaged 2404, 2663, 11.0, 89.0 and 666 microg/l respectively, while in the obese diabetic group (n=11), the corresponding values averaged 2441, 2580, 13.3, 85.1 and 610 microg/l respectively. Activities of antioxidant enzymes such as SOD, GPX and TAO were not significantly different in maternal veins of control and diabetic groups. Varying differences were noted in the case of antioxidant enzyme activities in umbilical blood samples of control and study groups. We conclude that obesity is not associated with significant alterations in antioxidant enzyme status in gestational diabetes and only with relatively minor alterations in status of some essential trace elements.
Acta Diabetol 2007 Sep
PMID:Maternal-foetal status of copper, iron, molybdenum, selenium and zinc in obese gestational diabetic pregnancies. 1772 48

The aim of this study is to investigate whether the prediction of all-cause mortality from traditional risk factors is improved by adding electrolytes (serum-phosphate (S-P), serum-calcium (S-Ca) and serum-magnesium (S-Mg)) in a Cox regression. The study uses an 18-year follow-up of patients (n=2504) referred by physicians in primary health care and hospitals to the Vindeln Patient Education (VPE) Center, mainly with a diagnosis of hypertension (HT), type 2 diabetes mellitus (DM) and/or obesity. Cox regression, with the latest registered value and baseline values for risk factors, was used to study all-cause mortality in men and women. 221 out of 1096 men and 157 out of 1408 women died during the 18-year follow-up (20% and 11% respectively). The Cox regression analysis reveals that high blood glucose (B-Glu) and low S-Mg were significantly associated with increased all-cause mortality in the whole patient population as well as in men and women separately. Among women, type 2 DM and systolic blood pressure (SBP) and among men, high S-Ca, S-P, S-urate and body mass index (BMI) were the main predictors of all-cause mortality. There is significantly improved prediction of all-cause mortality with electrolytes added to the traditional risk factors. High B-Glu and low S-Mg in both men and women, and high S-Ca and S-P in men, are significantly associated with all-cause mortality. The metabolic disturbance in this high-risk group of patients can be more fully understood if ionic imbalance is included in the prediction of mortatlity.
Acta Diabetol 2007 Sep
PMID:Prediction of all-cause mortality in a patient population with hypertension and type 2 DM by using traditional risk factors and serum-phosphate,-calcium and-magnesium. 1772 52


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