Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We aimed to define the detailed clinical features of Japanese childhood-onset Type 2 diabetes mellitus (T2DM) patients who were followed-up, and to determine whether discernable characteristics were dissimilar or not from those of adult- and childhood-onset T2DM in other countries. Subjects were 22 patients (10 males and 12 females) under treatment without HNF-1alpha or mitochondrial gene mutations, and who were apparently diagnosed as diabetic when less than 15 years of age. Body mass indexes at onset in boys and girls were 25.8 +/- 6.3 and 24.7 +/- 3.6, respectively, with mean ages 13.3 +/- 1.7 and 12.8 +/- 2.0 years, respectively. Most patients had a short diabetic duration that required insulin treatment. One or both parents of 18 of the 22 T2DM subjects were diabetic and 7 subjects had a history of diabetes in their family across three generations. We demonstrated that a relatively large number of Japanese childhood-onset T2DM cases have a strong genetic factor, and are not necessarily related to excessive obesity. Furthermore, most required insulin therapy in the initial stages because of insufficient pancreatic beta-cell reserves. This suggests that malfunction of pancreatic beta-cells triggers hyperglycemia resulting in the requirement for insulin in Japanese some childhood-onset T2DM patients.
Acta Diabetol 2007 Dec
PMID:Clinical and genetic features of childhood-onset Type 2 diabetes in Japan. 1776 98

Peroxisome proliferators-activated receptor gamma (PPAR gamma) is a nuclear hormone receptor that serves as a master regulator for adipocytes-specific genes contributing to adipocytes differentiation, insulin sensitivity and lipid metabolism. The substitution of proline to alanine at codon 12 of the PPAR gamma 2 gene (Pro12Ala polymorphism) is most widely studied, and the associations with diabetes, obesity, and other clinical parameters have been reported and discussed in several ethnic groups. Among native Qatar ethnicity, however, there is no report about this polymorphism. The aim of this study was to estimate the allele frequency of the Pro12Ala polymorphism of PPAR gamma 2 gene among Qatari population and investigate the association between this polymorphism and obesity or type 2 diabetes. This is a matched case-control study. It was carried out among diabetic patients and healthy subjects at the Primary Healthcare Clinics, and the survey was conducted from February 2003 to March 2006 in Qatari male and female nationals aged 35 to 60 years. The study was based on matched age, sex, and ethnicity of 400 cases (with diabetes) and 450 controls (without diabetes). Face-to-face interviews were based on a questionnaire that included variables such as age, sex, sociodemographic status, body mass index (BMI), and obesity. Their health status was assessed by medical conditions, family history, and blood pressure measurements. The allele frequency of Pro12Ala polymorphism in PPAR gamma 2 gene among Qataris is lower than that in many Caucasian ethnic groups. No association is seen between the Pro12Ala and type 2 Diabetes (0.055 vs 0.059, OR = 1.1311, P = 0.669). Nearly half of the diabetic type 2 patients (48.5%) were obese (BMI > 30) compared to nondiabetic subjects (29.8%) (P < 0.001). In this study, no association is seen between the Pro12Ala polymorphism in PPAR gamma 2 gene and the type 2 diabetes in Qatar.
Acta Diabetol 2008 Mar
PMID:Lack of association between the Pro12Ala polymorphism of the PPAR-gamma 2 gene and type 2 diabetes mellitus in the Qatari consanguineous population. 1780 73

We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From what can be gathered from the very few studies on the UPS in diabetic cardiovascular diseases published so far, the system seems to be functionally active to a different extent in the initiation, progression, and complication stage of atherosclerosis in the diabetic people. Further evidence for this theory, however, has to be given, for instance by specifically targeted antagonism of the UPS. Nonetheless, this hypothesis may help us understand why diverse therapeutic interventions, which have in common the ability to reduce ubiquitin-proteasome activity, can impede or delay the onset of diabetes and cardiovascular diseases (CVD). People with type 2 diabetes are disproportionately affected by CVD, compared with those without diabetes 1. The prevalence, incidence, and mortality from all forms of CVD (myocardial infarction, cerebro-vascular disease and congestive heart failure) are strikingly increased in persons with diabetes compared with those withoutdiabetes 2. Furthermore, diabetic patients have not benefited by the advances in the management of obesity, dyslipidemia, and hypertension that have resulted in a decrease in mortality for coronary heart disease (CHD) patients without diabetes 3. Nevertheless, these risk factors do not fully explain the excess risk for CHD associated with diabetes 45. Thus, the determinants of progression of atherosclerosis in persons with diabetes must be elucidated. Beyond the major risk factors, several studies have demonstrated that such factors, strictly related to diabetes, as insulin-resistance, post-prandial hyperglycemia and chronic hyperglycemia play a role in the atherosclerotic process and may require intervention 67. Moreover, it is important to recognize that these risk factors frequently "cluster" inindividual patients and possibly interact with each other, favouring the atherosclerosis progression toward plaque instability. Thus, a fundamental question is, "which is the common soil hypothesis that may unifying the burden of all these factors on atherosclerosis of diabetic patients? Because evidences suggest that insulin-resistance, diabetes and CHD share in common a deregulation of ubiquitin-proteasome system (UPS), the major pathway for nonlysosomal intracellular protein degradation in eucaryotic cells 89, in this review ubiquitin-proteasome deregulation is proposed as the common persistent pathogenic factor mediating the initial stage of the atherosclerosis as well as the progression to complicated plaque in diabetic patients.
Cardiovasc Diabetol 2007 Oct 30
PMID:The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes. 1797 Dec 5

The prevalence of obesity has been increasing dramatically in the last decades; the major metabolic complication of obesity is insulin resistance and type-2 diabetes because there are pathogenetic mechanisms linking obesity and type-2 diabetes. Diabetes is also rapidly increasing worldwide; such a description of the key stages in the evolution of type-2 diabetes may be of great interest for implementing antidiabetes treatment. In recent times, type-2 diabetes therapy has been based on drugs, which improve insulin sensibility or stimulate insulin secretion or slow down glucose absorption. Recently, an ADA and EASD consensus has been released to develop a common approach for the management of hyperglycaemia in adults. The development of new classes of blood-glucose-lowering medications to supplement the older therapies, such as lifestyle-directed interventions, insulin, sulfonylureas, and metformin, has increased the different possible options for the treatment of type-2 diabetes. Therapeutic approaches aiming to potentiate the biological effects of incretins include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-IV (DPP-IV) activity (incretin enhancers) will be very useful to slow down type-2 diabetes progression. Weight-loss interventions, such as a hypocaloric diet and physical exercise, in addition to agents such as orlistat, sibutramine and cannabinoid receptor antagonists, may have favourable effects upon fat storage, nutrient metabolism and ultimately glucose tolerance or type-2 diabetes. When the therapeutic target is not achieved, insulin with metformin could be suggested, but is this approach the ideal one for all patients? Perhaps it is possible to delay the initiation of insulin therapy, therefore, the actual and future therapeutical options are considered in the present review.
Acta Diabetol 2008 Jun
PMID:Time to insulin in type-2 diabetes: high hurdles or Santiago way? 1840 82

Type 2 diabetes mellitus (T2DM) is characterized by impaired insulin secretion, peripheral insulin resistance, and increased hepatic glucose production. Genes that contribute to genetic susceptibility to T2DM function in numerous biochemical pathways. Uncoupling protein-2 (UCP2) functions as a negative regulator of insulin secretion. Animal studies show induction of UCP2 plays a pathogenic role in the progression of obesity-induced T2DM and some human studies have shown an association between a common UCP2 polymorphism, Ala55Val (rs660339), and T2DM, obesity, and resting metabolic rate with the Val/Val genotype conferring increased risk. We investigated the relationship between the Ala55Val variant and incidence of T2DM among 12,056 participants in the Atherosclerosis Risk in Communities (ARIC) Study aged 45-64 years at baseline. Incident T2DM (n = 1,406) cases were identified over 9 years of follow-up. The Val55 allele frequency was 44% in blacks and 41% in whites. The rate of T2DM per 1,000 person was 15.0, 15.6, and 15.6 yearsfor Ala/Ala, Ala/Val, and Val/Val genotypes, respectively. We found no significant association between UCP2 genotypes and incident T2DM in the whole cohort, in race-gender subgroups, or in categories of body mass index (normal, overweight and obese). The Ala55Val polymorphism of UCP2 was not associated with incident T2DM in the ARIC cohort.
Acta Diabetol 2008 Sep
PMID:Lack of association between uncoupling protein-2 Ala55Val polymorphism and incident diabetes in the atherosclerosis risk in communities study. 1849 42

The incretin system has been shown to stimulate insulin secretion in a glucose dependent manner and currently fosters considerable hope for the treatment of diabetes. Recently, we have shown that the dipeptidylpeptidase-4 (DPP4) gene, which is responsible for incretin inactivation, was overexpressed in omental adipose tissue of obese men with the metabolic syndrome, compared to men not characterized by this condition. Since the cardiovascular disease (CVD) risk profile shows substantial inter-individual variability in obesity, this study aimed at verifying whether DPP4 polymorphisms contribute to explain such a difference. In the first step of this multi-stage study, seven tagging SNPs were genotyped in a sample of 576 obese (BMI>40 kg/m(2)) individuals and tested for their association with blood pressure and lipids, as well as diabetes-related phenotypes. Then, in an additional sample of 572 obese individuals (stage 2), SNPs showing trends (P<0.10) for an association in the first sample were genotyped and reanalyzed. Logistic regressions were used to compute odds ratio for obesity-related metabolic complications. In sample 1, homozygotes for rs17848915 and rs7608798 minor alleles were at lower risk of hyperglycemia/diabetes (P=0.002) and elevated plasma triglyceride levels (P=0.030) respectively, whereas rs1558957 heterozygotes were at higher risk to have high plasma triglyceride (P=0.040), HDL- (P=0.021), LDL- (P=0.001) and total-cholesterol (P=0.003) levels. However, none of these associations was consistently replicated in stage 2. This first comprehensive genetic analysis does not support the notion that DPP4 polymorphisms could modulate the CVD risk profile among obese patients.
Acta Diabetol 2009 Mar
PMID:Comprehensive genetic analysis of the dipeptidyl peptidase-4 gene and cardiovascular disease risk factors in obese individuals. 1868 83

Sleep disturbances may be associated with impaired glucose metabolism. The aim of this study was to evaluate sleep duration and quality in relation to glycemic control in patients with type 2 diabetes. In a cross-sectional study, sleep duration and quality were assessed in 47 middle-aged patients with type 2 diabetes treated with oral agents and without sleep disturbing complications and 23 healthy control subjects similar by age, sex, body mass index, occupation and schooling. Sleep was recorded by wrist-actigraphy for three consecutive days under free-living conditions. Univariate analysis showed lower sleep maintenance (P = 0.002) and sleep efficiency (P = 0.005), and higher fragmentation index (P < 0.0001), total activity score (P = 0.05) and moving time (P < 0.0001) in patients with type 2 diabetes. After adjusting for age, gender and schooling, fragmentation index and moving time remained significantly higher in the patients with diabetes (P < 0.05, both). HbA1c correlated inversely with sleep efficiency (r = -0.29; P = 0.047) and positively with moving time (r = 0.31; P = 0.031). These findings suggest that type 2 diabetes is associated with sleep disruptions even in the absence of complications or obesity. The relevance of sleep abnormalities to metabolic control and possible strategies to improve sleep quality in type 2 diabetes deserve further investigation.
Acta Diabetol 2008 Dec
PMID:Sleep abnormalities in type 2 diabetes may be associated with glycemic control. 1868 6

Serum glycated albumin (GA) is the clinical markers reflecting recent plasma glucose levels. We have previously clarified that serum GA levels are low for obesity and chronic inflammation is involved in the obesity-associated decrease in GA levels through acceleration of albumin catabolism. The present study investigated whether smoking, which is a representative factor that increases CRP, affects serum GA levels. One hundred and three male subjects with normal glucose tolerance (70 nonsmokers, 33 smokers) were enrolled in this study. Smokers and nonsmokers displayed no significant differences in fasting plasma glucose (FPG), oral glucose tolerance test 2-h glucose and HbA(1C). CRP levels were significantly higher in smokers than in nonsmokers (P < 0.05). Serum GA levels were significantly lower in smokers than in nonsmokers (P < 0.05). Stepwise multivariate regression analysis identified FPG and age as positively associated, and BMI and smoking as negatively associated with serum GA levels. In conclusion, serum GA levels were significantly lower in smokers than in nonsmokers. Smoking was identified as a significant negative explanatory variable for serum GA levels. These findings suggest that the inflammation-induced acceleration of albumin metabolism may be involved in the mechanism by which smoking is associated with serum GA levels.
Acta Diabetol 2009 Jun
PMID:Serum glycated albumin levels are influenced by smoking status, independent of plasma glucose levels. 1883 52

Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD). Several studies pointed out the possible role of increased leptin in NAFLD in humans. The aim of this study is to determine the effect of metformin on plasma leptin levels in obese patients with type 2 diabetes mellitus and NAFLD compared with lifestyle interventions. Thirty-four obese patients with newly diagnosed type 2 diabetes mellitus were prospectively followed for 6 months. All patients had ultrasonographic evidence of NAFLD at baseline. The patients were randomized into two groups: group 1 (n = 15) followed lifestyle changes only and group 2 (n = 19) received metformin (1,700 mg/day). At the end of treatment, BMI, WHR, HbA1c, fasting glucose, leptin, HOMA-IR, alanine aminotransferase values decreased in both groups. No significant difference in the end-points was observed between two groups. Only in group 2, LDL decreased and HDL increased significantly. Liver echogenity decreased significantly at the end of study in both groups. The percentage of patients who no longer had evidence of NAFLD was not significantly different between the groups (20% of patients on lifestyle intervention vs. 16% of patients on metformin). The data demonstrate that, metformin and lifestyle interventions equally affected the plasma leptin levels, BMI and degree of NAFLD in obese patients with type 2 diabetes mellitus. In addition, the effects of metformin on the variables were not found to be mediated by leptin.
Acta Diabetol 2009 Jun
PMID:The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. 1883 53

Insulin resistance (IR) and obesity may be associated with impaired response to physical exercise. We aimed at assessing physical capacity in obese children with biopsy proven non-alcoholic fatty liver disease (NAFLD) as compared to normal weight and obese children without fatty liver disease. All male subjects, 20 NAFLD and 31 control individuals (20 obese, without NAFLD and 11 normal weight children) took part in the study. We evaluated changes in cardiovascular parameters during a bicycle-ergometer exercise test (James' test). Duration, power of exercise, heart rate (HR), blood pressure (BP), pulse pressure, cardiac output ((I)CO) and total peripheral vascular resistance indexed for height ((I)TPVR) were recorded at rest ((r)) and peak ((p)) exercise. The homeostatic model assessment was used to determine insulin resistance (HOMA-IR) and beta-cell action (HOMA-beta cell). In NAFLD and obese subjects, fasting leptin, insulin secretion, insulinogenic index (IGI), muscle insulin sensitivity (MISI) and hepatic insulin resistance index (HIRI) were assayed. Children with NAFLD were the most insulin-resistant (P = 0.001), and showed higher HIRI than obese controls (P = 0.05). At rest, they had the lowest values of SBP(r) (P = 0.001 vs. controls and P < or = 0.05 vs. obese controls); during the test, the highest values of (I)CO(p) (P = 0.005), Delta(I)CO (P = 0.003) and DeltaTRVP(p) (P < or = 0.0001). NAFLD and obese controls both had impaired DeltaHR(p) (P < or = 0.0001). However, obese controls were not able to reduce peripheral resistance during the test. HOMA-IR explained 28% of variance in Delta(I)CO of the whole sample, (P < or = 0.0001). In obese children with or without NAFLD, increased IR and body weight may induce cardiovascular compensatory changes in response to physical exercise with fairly different pathogenetic mechanisms, which are likely to be dependent on the different degree of IR.
Acta Diabetol 2009 Jun
PMID:Insulin resistance and exercise capacity in male children and adolescents with non-alcholic fatty liver disease. 1883 55


<< Previous 1 2 3 4 5 6 7 8 9 10