Tenomodulin is associated with obesity and diabetes risk: the Finnish diabetes prevention study

We recently showed that long-term weight reduction changes the gene expression profile of adipose tissue in overweight individuals with impaired glucose tolerance (IGT). One of the responding genes was X-chromosomal tenomodulin (TNMD), a putative angiogenesis inhibitor. Our aim was to study the associations of individual single nucleotide polymorphisms and haplotypes with adiposity, glucose metabolism, and the risk of type 2 diabetes (T2D). Seven single nucleotide polymorphisms from two different haploblocks were genotyped from 507 participants of the Finnish Diabetes Prevention Study (DPS). Sex-specific genotype effects were observed. Three markers of haploblock 1 were associated with features of adiposity in women (rs5966709, rs4828037) and men (rs11798018). Markers rs2073163 and rs1155794 from haploblock 2 were associated with 2-hour plasma glucose levels in men during the 3-year follow-up. The same two markers together with rs2073162 associated with the conversion of IGT to T2D in men. The risk of developing T2D was approximately 2-fold in individuals with genotypes associated with higher 2-hour plasma glucose levels; the hazard ratios were 2.192 (p = 0.025) for rs2073162-A, 2.191 (p = 0.027) for rs2073163-C, and 1.998 (p = 0.054) for rs1155974-T. These results suggest that TNMD polymorphisms are associated with adiposity and also with glucose metabolism and conversion from IGT to T2D in men.     

Correlates of health-related quality of life in overweight and obese adults with type 2 diabetes

Objective: This paper describes and examines conceptually relevant correlates of health‐related quality of life (HRQL) in overweight or obese persons with type 2 diabetes. Research Design and Procedures: The investigation was a cross‐sectional study of 5145 overweight or obese adults with type 2 diabetes between the ages of 45 and 74 years. Analyses examined the relationship that demographic characteristics, disease burden, and cardiovascular fitness had with HRQL: the Short Form 36 (SF‐36) and the Beck Depression Inventory (BDI) II. Results: Means for the SF‐36 physical component summary (PCS) scores, the mental component summary scores, and the BDI‐II were as follows: 47.0, 54.0, and 5.7. Less desirable PCS scores were related to several comorbidities, insulin use, physical complaints, a high BMI, low metabolic equivalent (MET) capacity, and lower education. Interactions between categories of obesity and MET capacity revealed that greater BMI was related to lower PCS scores when individuals had lower MET capacities yet was absent for those individuals who had higher MET capacities. In addition, although greater BMI was associated with more severe depressive symptomatology, this association was the most dramatic for those with class III obesity who had low MET capacity. Discussion: Although participants in Look AHEAD had a favorable profile on the SF‐36 and the BDI‐II at baseline, lower PCS scores were related to disease severity and the presence of other comorbidities. More important, although the temporal ordering of associations cannot be determined in a cross‐sectional design, the interactions between obesity class and MET capacity suggest that the adverse effect of BMI on PCS and BDI‐II scores may be buffered by higher MET capacities.     

Genetic predisposition for Type 2 diabetes, but not for overweight/obesity, is associated with a restricted adipogenesis

Background

Development of Type 2 diabetes, like obesity, is promoted by a genetic predisposition. Although several genetic variants have been identified they only account for a small proportion of risk. We have asked if genetic risk is associated with abnormalities in storing excess lipids in the abdominal subcutaneous adipose tissue.

Methodology/Principal Findings

We recruited 164 lean and 500 overweight/obese individuals with or without a genetic predisposition for Type 2 diabetes or obesity. Adipose cell size was measured in biopsies from the abdominal adipose tissue as well as insulin sensitivity (HOMA index), HDL-cholesterol and Apo AI and Apo B. 166 additional non-obese individuals with a genetic predisposition for Type 2 diabetes underwent a euglycemic hyperinsulinemic clamp to measure insulin sensitivity. Genetic predisposition for Type 2 diabetes, but not for overweight/obesity, was associated with inappropriate expansion of the adipose cells, reduced insulin sensitivity and a more proatherogenic lipid profile in non-obese individuals. However, obesity per se induced a similar expansion of adipose cells and dysmetabolic state irrespective of genetic predisposition.

Conclusions/Significance

Genetic predisposition for Type 2 diabetes, but not obesity, is associated with an impaired ability to recruit new adipose cells to store excess lipids in the subcutaneous adipose tissue, thereby promoting ectopic lipid deposition. This becomes particularly evident in non-obese individuals since obesity per se promotes a dysmetabolic state irrespective of genetic predisposition. These results identify a novel susceptibility factor making individuals with a genetic predisposition for Type 2 diabetes particularly sensitive to the environment and caloric excess.     

The polymorphisms of UCP1 genes associated with fat metabolism,obesity and diabetes

Uncoupling protein 1 (UCP1), a 32-kDa protein located in the inner mitochondrial membrane, is abundant in brown adipose tissue, as a proton transporter in mitochondria inner membrane which uncouples oxidative metabolism from ATP synthesis and dissipates energy through the heat. UCP1 has been reported to play important roles for energy homeostasis in rodents and neonate of larger mammals including human. Recently, numerous candidate genes were searched to determine the genetic factors implicated in the pathogenesis of obesity, related metabolic disorders and diabetes. UCP-1, which plays a major role in thermogenesis, was suggested to be one of the candidates. This review summarizes data supporting the existence of brown adipocytes and the role of UCP1 in energy dissipation in adult humans, and the genetic variety association with the fat metabolism, obesity and diabetes.     

The association between overweight/obesity and psychological distress: A population based cross-sectional study in Saudi Arabia

ObjectivesThe objective of this study was to compare the association between mental well-being between obese (classes 1 and 2), over-weight and non-obese population-based individualsMethodsA population-based cross-sectional study was conducted in Al-Kharj, Saudi Arabia. A total of 1019 Saudi nationals aged ≥ 18 years participated in the survey. BMI scores were used to categorize participants into three groups: Obese, overweighted and non-obese/non-overweight. Mental well-being was evaluated by using the validated Arabic version of the General Health Questionnaire version 12 (GHQ-12).ResultsWe used total GHQ score (Mean=12; SD=5.23) to compare mental well-being between the four BMI class categories. The overall one-way ANOVA model was statistically significant (F = 7.018, d = 6, P < 0.001). In multivariate analysis, after adjusting for sociodemographic variables, diabetes and smoking statuses we found that higher psychological distress (as evident by a higher total GHQ score) was associated with higher BMI. The unstandardized Beta regression coefficient = 2.627; P = 0.034). Females were more likely to have higher psychological distress than males (unstandardized Beta = 1.466, P = 0.003). Job status whether being unemployed or ‘civilian’ (civil worker) was significantly associated with higher psychological distress (unstandardized Beta = 1.405, P = 0.041). Being diabetic has a 1.6 times higher risk of psychological distress (unstandardized Beta = 1.604, P = 0.027).ConclusionThe study highlights the public health implications of psychological distress amongst individuals with overweight and obesity in Saudi Arabia. Future longitudinal studies should explore the temporality of this relationship.     

The influence of obesity on falls and quality of life

Objective

To determine (1) whether obese older adults had higher prevalence of falls and ambulatory stumbling, impaired balance and lower health-related quality of life (HRQL) than their normal weight counterparts, and (2) whether the falls and balance measures were associated with HRQL in obese adults.

Methods

Subjects who had a body mass index (BMI) greater than 30 kg/m² were classified into an obese group (n = 128) while those with BMI between 18.5 and 24.9 kg/m² were included into a normal weight group (n = 88). Functional tests were performed to assess balance, and questionnaires were administered to assess history of falls, ambulatory stumbling, and HRQL.

Results

The obese group reported a higher prevalence of falls (27% vs. 15%), and ambulatory stumbling (32% vs. 14%) than the normal weight group. Furthermore, the obese group had lower HRQL, (p ≤ 0.05) for physical function (63 ± 27 vs. 75 ± 26; mean ± SD), role-physical (59 ± 40 vs. 74 ± 37), vitality (58 ± 23 vs. 66 ± 20), bodily pain (62 ± 25 vs. 74 ± 21) and general health (64 ± 19 vs. 70 ± 18). In the obese group, a history of falls was related (p ≤ 0.05) to lower scores in 4 domains of HRQL, and ambulatory stumbling was related (p ≤ 0.01) to 7 domains.

Conclusion

In middle-aged and older adults, obesity was associated with a higher prevalence of falls and stumbling during ambulation, as well as lower values in multiple domains of HRQL. Furthermore, a history of falls and ambulatory stumbling were related to lower measures of HRQL in obese adults.

     

Racial/ethnic differences in the prevalence of gestational diabetes mellitus and maternal overweight and obesity,by Nativity,Florida, 2004‐2007

Objective:

We examined the risk of gestational diabetes mellitus (GDM) among foreign‐born and U.S.‐born mothers by race/ethnicity and BMI category.

Design and Method:

We used 2004‐2007 linked birth certificate and maternal hospital discharge data of live, singleton deliveries in Florida to compare GDM risk among foreign‐born and U.S.‐born mothers by race/ethnicity and BMI category. We examined maternal BMI and controlled for maternal age, parity, and height.

Results:

Overall, 22.4% of the women in our study were foreign born. The relative risk (RR) of GDM among women who were overweight or obese (BMI ≥ 25.0 kg m^?2) was higher than among women with normal BMI (18.5‐24.9 kg m^?2) regardless of nativity, ranging from 1.3 (95% confidence interval (CI) = 1.0, 1.9) to 3.8 (95% CI = 2.1, 7.2).Foreign‐born women also had a higher GDM risk than U.S.‐born women, with RR ranging from 1.1 (95% CI = 1.1, 1.2) to 2.1 (95% CI = 1.4, 3.1). This finding was independent of BMI, age, parity, and height for all racial/ethnicity groups.

Conclusions:

Although we found differences in age, parity, and height by nativity, these differences did not substantially reduce the increased risk of GDM among foreign‐born mothers. Health practitioners should be aware of and have a better understanding of how race/ethnicity and nativity can affect women with a high risk of GDM. Although BMI is a major risk factor for GDM, it does not appear to be associated with race/ethnicity or nativity.

     

Major gene mutations associated with obesity and diabetes mellitus

Obesity and diabetes mellitus are associated with low or elevated serum leptin and insulin levels (U-like relation). Mutations in LEP and INS are linked to decreases in leptin and insulin while mutations in LEPR and INSR are linked to their increase. Homozygous LEP mutations are associated with the early onset of severe obesity and the diverse impairment of physiological functions. The recessive LEPR mutations are associated with similar pathology in homozygous state. Missense mutations of INS are dominant and induce the synthesis of chimeric proinsulin, which may interfere with the folding and processing of active insulin molecules. In the heterozygous state, they cause insulin deficiency and PND. Recessive INS mutations do not induce the synthesis of anomalous proinsulin, and they are only associated with PND in the homozygous state. Mutations of INSR induce insulin resistance, lipodystrophy, other pathologies, and suggest the important role of insulin in glucose level regulation and in the stimulation of fat accumulation.     

体质测量在超重和肥胖研究中的应用

本文通过查阅文献,对体质测量在评估超重、肥胖和预测健康风险中的应用进行了回顾性调查、总结和分析,并对体质量指数、体脂肪指数和内脏脂肪指数等测量指标的优势和局限性进行了分析和讨论.由于预测结果受多种因素的影响,因而预测评价时应根据不同地域的不同的研究对象和不同的预测风险,选用不同的测量指标和不同的测量工具.为同行们今后应...