Inhibition of Cortisol Secretion by Dexamethasone in Relation to Body Fat Distribution: A Dose-Response Study

In this study, dexamethasone (dex) was administered in random order in doses of 0.05, 0.125, 0.25 and 0.5 mg at 10 p.m. with measurements of serum Cortisol in the morning (8 a.m.) of this and the following day. The test was performed on 22 apparently healthy men, 40 to 60 years of age, recruited from laboratory personnel, outpatient clinics or advertisements in a newspaper. Eight had a body mass index (BMI) (kg/m²) of <25 and 14 of >25. Twelve men had a waist hip ratio (WHR) of <1.0 and 10 men had a WHR of<1.0. Cortisol values at baseline were correlated inversely with WHR and were usually lower in men with a high (>1.0) rather than a low than low (<1.0) WHR after dex inhibition. There was apparently no inhibition by dex at 0.05 and 0.125 mg on average in men with a WHR of >1.0. In addition, the inhibition at 0.5 mg dex correlated negatively with the WHR and was significantly lower (p<0.05) in men with a WHR of >1.0 than in men with a WHR of <1.0. None of these differences or relationships was found to be dependent on BMI. It is concluded that men with an elevated WHR experience a decrease in the inhibition of Cortisol secretion by dex. It is suggested that this could explain or contribute to the elevated sensitivity of their HPA axis. Furthermore, lower morning Cortisol concentrations suggest a change in diurnal secretion patterns.     

Mendelian randomization analysis of the causal impact of body mass index and waist-hip ratio on rates of hospital admission

We analyze how measures of adiposity – body mass index (BMI) and waist hip ratio (WHR) – causally influence rates of hospital admission. Conventional analyses of this relationship are susceptible to omitted variable bias from variables that jointly influence both hospital admission and adipose status. We implement a novel quasi-Poisson instrumental variable model in a Mendelian randomization framework, identifying causal effects from random perturbations to germline genetic variation. We estimate the individual and joint effects of BMI, WHR, and WHR adjusted for BMI. We also implement multivariable instrumental variable methods in which the causal effect of one exposure is estimated conditionally on the causal effect of another exposure. Data on 310,471 participants and over 550,000 inpatient admissions in the UK Biobank were used to perform one-sample and two-sample Mendelian randomization analyses. The results supported a causal role of adiposity on hospital admissions, with consistency across all estimates and sensitivity analyses. Point estimates were generally larger than estimates from comparable observational specifications. We observed an attenuation of the BMI effect when adjusting for WHR in the multivariable Mendelian randomization analyses, suggesting that an adverse fat distribution, rather than a higher BMI itself, may drive the relationship between adiposity and risk of hospital admission.     

Waist-to-hip ratio versus body mass index as predictors of fitness in women

The claim that men prefer women with low waist-to-hip ratios (WHR) has been vigorously disputed. We examine self-report data from 359 primiparous Polish women (with normal singleton births and healthy infants) and show that WHR correlates with at least one component of a woman’s biological fitness (her first child’s birth weight, a variable that significantly affects infant survival rates). However, a woman’s Body Mass Index (BMI) is a better predictor of her child’s neonatal weight in small-bodied women (<54 kg). The failure to find a preference for low WHR in some traditional populations may thus be a consequence of the fact that, even in western populations, body mass is a better predictor of fitness in those cases characterized by low maternal body weight. Boguslaw Pawłowski Ph.D., D.Sc., is a researcher and lecturer in biological anthropology at the University of Wrocław, Poland. His research interests focus on mechanisms of human evolution (with special attention to the evolution of subcutaneous fat tissue distribution) and human mate choice. Robin Dunbar Ph.D., FBA is British Academy Research Professor of Evolutionary Psychology at the University of Liverpool, England, and co-Director of the British Academy Centenary Research Project. His research interests focus on the evolutionary and environmental determinants of social and reproductive strategies, with particular references to humans, nonhuman primates, and ungulates.     

Identification of a novel duplication CFTRdup2 and functional impact of large rearrangements identified in the CFTR gene

The aim of this study was to investigate associations of two candidate gene SNPs of the endocannabinoid receptor type 1 gene (CNR1) with overweight, obesity and obesity-related traits in Chinese retired women. The study subjects were a subsample of the Taizhou Retiree Women Cohort, consisting of 2812 retired women aged 50-64 years recruited from Taizhou, Jiangsu, China. Neither rs2023239 nor rs806381 polymorphism was significantly associated with body mass index-defined overweight and obesity or waist-to-hip-ratio-defined obesity. For obesity-related traits, rs2023239 was significantly associated with glutamate pyruvate transaminase (GPT) (median, 18.00 vs 17.00 for TT and TC genotypes, respectively, P=0.043). The rs806381 also showed significant association with triglyceride (TG) (mean±SD, 1.46±0.20 vs 1.53±0.20 for GA and GG+AA genotypes, respectively, P=0.013) under the dominant genetic model. In conclusion, the rs2023239 and rs806381 polymorphisms of CNR1 were not associated with increased overweight and obesity risk. But the rs2023239 polymorphism was significantly associated with GPT, and the rs806381 polymorphism was significantly associated with TG.     

The influence of adipose tissue location on postural control

A growing body of evidence suggests, that excessive body weight is inseparably connected with postural instability. In none of previous studies, body weight distribution has been considered as a factor, which may affect results of a static posturography. The purpose of the present study is to quantify some center of foot pressure (COP) characteristics in 40 obese women with android type of obesity (waist-to-hip ratio - WHR ≥ 0.85, BMI: 37.5 ± 5.4) and 40 obese women with gynoid type of obesity (WHR < 0.85, BMI: 36.9 ± 5.1). Variables of postural sway were acquired while subjects were standing quietly on a force plate with eyes open and closed. Both in the sagittal and frontal plane sway range, average velocity, and maximal velocity of COP were calculated. Moreover, the total average velocity and total maximal velocity of the COP displacement were computed.Women with abdominal obesity showed a larger sway range in the anterior-posterior plane with eyes open (p < 0.0282) and eyes closed conditions (p < 0.0115) and a greater maximal COP velocity to compare with subjects with gynoidal obese type (p < 0.0112) with eyes closed condition.The postural stability in obese women from the biomechanical point of view is strongly dependent on body distribution. Women with the abdominal obesity type may be exposed to a greater risk of postural instability as compare to women with gynoid fat distribution.     

Waist Circumference as the Best Predictor of Noninsulin Dependent Diabetes Mellitus (NIDDM) Compared to Body Mass Index,Waist/hip Ratio and Other Anthropometric Measurements in Mexican Americans—A 7-Year Prospective Study

Although a number of obesity-related variables are recognized risk factors for NIDDM, few studies have addressed which one is the best predictor. A cohort of 721 Mexican Americans aged 25–64 years who were free of NIDDM at baseline were followed for an average of 7.2 years; 105 new cases of NIDDM were diagnosed. Body weight, body mass index (BMI), waist and hip circumferences, waist/hip ratio (WHR), triceps and subscapular skinfolds were all positively predictive of NIDDM independent of age and sex. There were modest to strong correlations between these anthropometric variables, however, waist circumference was the strongest predictor of NIDDM. The predictive power of a single measurement of waist circumference was at least equal to that of WHR and BMI combined. The risk of NIDDM for those in the highest quartile of waist circumference was 11 times greater than for those in the lowest quartile (95% confidence interval: 4.2–28.8). The waist-NIDDM relation was stronger in subjects with BMI ≤ 27 kg/m² (OR: 6.0 for a 1 SD difference) than in subjects with BMI > 27 kg/m2 (OR: 1.7 for a 1 SD difference). In multivariate analysis, waist circumference was the only significant predictor of NIDDM in models that included other anthropometric variables either separately or simultaneously. WHR and BMI were independent predictors of NIDDM after adjustment for each other, however, their predictive abilities disappeared after adjustment for waist circumference. The data indicate that waist is the best obesity-related predictor of NIDDM. This finding suggests that the distribution of body fat, especially abdominal localization, is a more important determinant than the total amount of body fat of the development of NIDDM in Mexican Americans.     

Pro-inflammatory cytokine gene polymorphisms and threat for coronary heart disease in a North Indian Agrawal population

The association of IFN-γ (+ 874 A/T; rs2430561), TNF-α (− 308 G/A; rs1800629) and TNF-β (+ 252 A/G; rs909253) with Coronary Heart Disease (CHD) has not been rigorously tested in Indian population. In the present study we sought to examine the role of these cytokines in the causation of CHD and their association with conventional CHD risk factors. A total of 138 case and 187 unrelated healthy controls aged 35 to 80 years, matched on ethnicity and geography were collected from North Indian Agrawal population. Single nucleotide polymorphisms at the promoter TNF-α − 308 G/A and the intronic IFN-γ + 874 A/T were analyzed by allele-specific PCR, and the intronic TNF-β + 252 A/G was analyzed by RFLP. Of the three selected polymorphisms, genotypic distribution of IFN-γ + 874 A/T and TNF-β + 252 A/G polymorphisms was significantly different between patients and controls in the present study. OR revealed statistically significant risk for CHD with respect to IFN-γ + 874 T allele, whereas OR for TNF-β + 252 A/G showed three fold risk in homozygous condition though not significant. No such trend could be observed for TNF-α − 308 G/A polymorphism. Multivariate logistic regression after adjusting for all the confounders showed significant risk for CHD with the genotypes and genotypic combinations of all the three markers (albeit not significant with TNF-α). Increased risk for CHD was likely to be associated with interaction of IFN-γ with diastolic hypertension, TNF-α with diabetes and BMI, and TNF-β with serum triglyceride and very low density lipoprotein (VLDL) levels. The results suggest that these selected cytokine polymorphisms could possibly serve as potential bio-markers for CHD in conjunction with specific conventional risk factors.     

Is there any association of apolipoprotein E gene polymorphism with obesity status and lipid profiles? Tehran Lipid and Glucose Study (TLGS)

Aims

Considering the key role played by the apolipoprotein E (Apo E) gene in the regulation of lipid metabolism and obesity, the current study has evaluate the association between abdominal obesity and Apo E gene polymorphism in a population of Tehran.

Materials and methods

A cross-sectional study was performed on 345 men and 498 women, aged 19–86 years, selected from among participants of the Tehran Lipid and Glucose Study. The RFLP-PCR technique was employed to investigate polymorphism in the gene fragments. Based on the national survey of risk factors for non-communicable diseases of Iran, waist circumference (WC) cut off was set at 89 cm for men and 91 cm for women. The risk effect of obesity related variables and lipid profiles in two groups of WC were examined by logistic regression. For body mass index (BMI), waist to hip ratio (WHR), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), fasting blood sugar (FBS), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and blood pressure (BP), the standard risk cut-offs were applied.

Results

Frequencies of E2, E3, and E4 alleles were 9.7, 73, and 14.6%, respectively. The presence of the E3 allele was significantly associated with higher TG level in subjects with high WC, while, the presence of E4 allele decreased the plasma HDL-C (E2:52.1 ± 13.1 vs., E3:48.9 ± 11.2 vs., E4:44.6 ± 10.6 mg/dl, p < 0.05), HDL-C2 (E2:20.4 ± 9.2 vs., E3:19.1 ± 8.8 vs., E4:16.3 ± 7.9 mg/dl, p < 0.05), and HDL-C3 (E2:32.1 ± 7.4 vs., E3:30.3 ± 6.2 vs., E4:28.3 ± 6.1 mg/dl, p < 0.05) in normal WC subjects. The presence of the E3 carrier increased the risk of having higher plasma TG, compared with the E2 carrier (95% CI OR = 1.91, 1.02–3.57; p = 0.04).

Conclusion

According to the results of this study, the E3 carrier, caused an approximately 90% increase in the levels of TG in the group with abdominal obesity.     

The calcium-sensing receptor R990G polymorphism is associated with increased risk of hypertriglyceridemia in obese Chinese

Background

We have demonstrated that the calcium-sensing receptor (CaSR) is involved in lipid metabolism; however, whether CaSR polymorphisms affect lipid metabolism in obesity is still unclear. The present study aimed to determine the effects of CaSR polymorphisms on HTG risk in obese Chinese.

Methods

A total of 972 subjects with HTG and 1197 with normal triglyceride (NTG) were stratified by body mass index (BMI) into normal weight, overweight or obesity subgroups. After 12-h fasting, CaSR polymorphisms in exon 7 were determined in the blood. Serum lipids and glucose, as well as height, body weight and waist circumference were measured. The anthropometric and metabolic characteristics of the NTG subjects were re-evaluated 3 years later.

Results

There were no genotypic or allelic distribution differences for the A986S or Q1011E polymorphisms between the NTG and HTG groups. However, the G/G genotypic and G allelic distributions of the CaSR R990G polymorphism in the HTG group were higher than the NTG group (p < 0.001). After stratification, in obese subjects, the homozygous (G/G) distribution of the CaSR R990G polymorphism in the HTG group was significantly higher than in the NTG group (p = 0.001), and showed an increased risk of HTG at baseline [OR = 2.55, 95% CI = 1.65–3.92, p < 0.006]. Interaction of the CaSR R990G polymorphism with BMI was associated with increased risk of HTG (β = 0.927, p < 0.001). Re-evaluation of the NTG subjects revealed significantly increased serum triglyceride levels in obese homozygous versus wildtype carriers (p < 0.05).

Conclusions

These results suggest that the CaSR R990G polymorphism is associated with increased risk of HTG, especially in obese Chinese, and may be a potential genetic predictor of diseases related to HTG.     

Elevated circulating vaspin levels were decreased by rosiglitazone therapy in T2DM patients with poor glycemic control on metformin alone

Vaspin has been regarded as a novel adipokine with potential insulin sensitizing properties. The aim of the present study is to investigate the effects of rosiglitazone therapy on plasma vaspin in type 2 diabetes patients (T2DM) inadequately controlled on metformin alone. A total of 105 subjects, including 37 subjects with normal glucose tolerance (NGT), 37 subjects with impaired glucose regulating (IGR), and 31 T2DM patients with poor glycemic control on metformin alone were enrolled in this study. Fasting plasma vaspin levels were higher in T2DM patients with poor glycemic control than that in IGR and NGT groups (1.19 ± 0.74 vs. 0.46 ± 0.26 and 0.54 ± 0.28 μg/L, P < 0.05). There was no difference between IGR and NGT groups. In T2DM patients, fasting plasma vaspin concentrations were significantly decreased after rosiglizatone therapy for 12 weeks (1.19 ± 0.74 vs. 0.91 ± 0.54 μg/L, P < 0.05), accompanied with significant amelioration of insulin sensitivity and glucose control. Plasma vaspin levels were positively associated with the fasting insulin and the homeostasis model assessment of IR (HOMA-IR). In conclusion, plasma vaspin level is higher in T2DM patients with poor glycemic control. And rosiglitazone therapy decreased plasma vaspin levels through glucose and insulin sensitivity regulation.