Perceived Stress and Weight Gain in Adolescence: A Longitudinal Analysis

Although perceived stress has been hypothesized to be a risk factor for obesity, epidemiological studies relating stress to weight gain have shown mixed results. We examined prospective associations between perceived stress and changes in waist circumference and BMI in a large study of adolescents. As part of the Health and Behaviour in Teenagers Study (HABITS), height, weight, and waist circumference were measured annually in 4,065 adolescents aged from 11 to 16. Waist and BMI standard deviation scores (SDS) were used as indices of adiposity. Adolescents completed a measure of perceived stress each year, from which mean stress scores over the 5‐year period were also calculated and divided by tertile into lower, moderate, and higher stress. Associations between perceived stress at each year and adiposity 1–4 years later and also adiposity trajectories over the whole period in relation to mean stress were investigated. Analyses were adjusted for age, sex, ethnicity, socioeconomic deprivation, pubertal timing, and smoking. Perceived stress in any year was not related prospectively to increases in waist or BMI SDS 1–4 years later, nor was there any evidence that higher stress over the whole period was associated with greater gains in waist or BMI SDS. However, waist and BMI SDS were significantly higher in the moderate‐ and higher‐stress groups than the lower‐stress group across the whole 5‐year period. Persistent stress was associated with higher waist circumference and BMI in adolescence, but did not lead to differential changes over 5 years.     

A Prospective Study of Adiposity and All‐Cause Mortality: The Malmö Diet and Cancer Study

Objective: This study aims to examine the association between various measures of adiposity and all‐cause mortality in Swedish middle‐aged and older men and women and, additionally, to describe the influences of age and sex on these associations. Research Methods and Procedures: A prospective analysis was performed in a cohort of 10,902 men and 16,814 women ages 45 to 73 years who participated in the Malmö Diet and Cancer Study in Sweden. Baseline examinations took place between 1991 and 1996, and 982 deaths were documented during an average follow‐up of 5.7 years. All‐cause mortality was related to the following variables measured at baseline: body mass index (BMI), percentage of body fat, lean body mass (LBM), and waist‐to‐hip ratio (WHR), with adjustment for age and selected covariates. Body composition data were derived from bioelectrical impedance analysis. Results: The association between percentage of body fat and mortality was modified by age, particularly in women. For instance, fatness was associated with excess mortality in the younger women but with reduced mortality in the older women. Weaker associations were seen for BMI than for percentage of body fat in both sexes. Placement in the top quintiles of waist‐to‐hip ratio, independent of overall body fat, was a stronger predictor of mortality in women than in men. The observed associations could not be explained by bias from early death or antecedent disease. Discussion: The findings reveal sex and age differences for the effects of adiposity and WHR on mortality and indicate the importance of considering direct measures of adiposity, as opposed to BMI, when describing obesity‐related mortality risks.     

Relationships of Age and Weekly Running Distance to BMI and Circumferences in 41, 582 Physically Active Women

Objective: To assess in women whether age‐related increases in adiposity are dependent on exercise, and, contrariwise, whether exercise‐related declines in adiposity are dependent on age. Research Methods and Procedures: Cross‐sectional analyses were conducted of 41, 582 female runners. Results: Age affected the relationships between vigorous exercise and adiposity. The decline in BMI per kilometer per week run was linear in 18 to 23 year olds and became increasingly non‐linear (convex) with age. Waist, hip, and chest circumferences declined significantly with running distance across all age groups, but the declines were significantly greater in older than younger women, particularly among shorter distance runners. The relationships between body circumferences and running distance became increasingly convex in older women. Conversely, vigorous exercise diminished the apparent increase in adiposity with age. The increase in average BMI with age was greatest in women who ran <8 km/wk, intermediate in women who ran 8 to 15 km/wk or 16 to 31 km/wk, and least in those who averaged over 32 km/wk. Before age 45, waist circumference rose for those who ran 0 to 7 km/wk, showed no significant relationship to age for those who ran 8 to 39 km/wk, and declined in those who ran 40 to 55 and 56 km/wk and more. Age related‐increases in hip and chest circumferences before 45 years old were significantly less in women who ran longer weekly distances. Discussion: These cross‐sectional associations are consistent with the hypothesis that exercise may mitigate age‐related increases in adiposity and that age affects exercise‐induced reductions in adiposity (although causality remains to be determined experimentally).     

F2-isoprostanes and adiposity in older adults

We examined whether a systemic marker of oxidative stress, F₂‐isoprostanes (F₂‐IPs), was associated with total and regional adiposity, adipocytokines, and change in adiposity. Using data from 726 participants enrolled in the Health, Aging, and Body Composition (Health ABC) study, F₂‐IPs and adipocytokines were measured from baseline plasma samples. Total adiposity was measured by whole‐body dual‐energy X‐ray absorptiometry and regional adiposity by abdominal and thigh computed tomography scans at baseline and 5‐year follow‐up. ANOVA models were estimated to examine associations between F₂‐IP tertiles and baseline adiposity and changes in body composition. Median F₂‐IPs was 54.3 pg/ml; women had significantly higher levels than men (61.5 vs. 48.9 pg/ml, P < 0.001). F₂‐IPs were associated with higher levels of adiponectin, leptin, and tumor necrosis factor‐α (TNF‐α). Positive associations were found between F₂‐IPs and all measures of total and regional adiposity among women. In linear regression models, adipocytokines mediated associations among women. Over 5 years of follow‐up, women in the highest vs. lowest F₂‐IP tertile exhibited significant loss of weight (lowest tertile: ?1.1 kg, highest tertile: ?2.7 kg, P < 0.05). In conclusion, F₂‐IPs were associated with measures of total and regional adiposity in women alone and these associations were partially explained by adipocytokines. F₂‐IPs predicted loss of total adiposity over time among women.     

Comparison of Overall Obesity and Body Fat Distribution in Predicting Risk of Mortality

Results of studies comparing overall obesity and abdominal adiposity or body fat distribution with risk of mortality have varied considerably. We compared the relative importance and joint association of overall obesity and body fat distribution in predicting risk of mortality. Participants included 5,799 men and 6,429 women aged 30–102 years enrolled in the third National Health and Nutrition Examination Survey who completed a baseline health examination during 1988–1994. During a 12‐year follow‐up (102,172 person‐years), 1,188 men and 925 women died. In multivariable‐adjusted analyses, waist‐to‐thigh ratio (WTR) in both sexes (P_trend <0.01 for both) and waist‐to‐hip ratio (WHR) in women (P_trend 0.001) were positively associated with mortality in middle‐aged adults (30–64 years), while BMI and waist circumference (WC) exhibited U‐ or J‐shaped associations. Risk of mortality increased with a higher WHR and WTR among normal weight (BMI 18.5–24.9 kg/m²) and obese (BMI ≥30.0 kg/m²) adults. In older adults (65–102 years), a higher BMI in both sexes (P_trend <0.05) and WC in men (P_trend 0.001) were associated with increased survival, while remaining measures of body fat distribution exhibited either no association or an inverse relation with mortality. In conclusion, ratio measures of body fat distribution are strongly and positively associated with mortality and offer additional prognostic information beyond BMI and WC in middle‐aged adults. A higher BMI in both sexes and WC in men were associated with increased survival in older adults, while a higher WHR or WTR either decreased or did not influence risk of death.     

Skinfolds and coronary heart disease risk factors are more strongly associated with BMI than with the body adiposity index

Objective:

A recent, cross‐sectional analysis of adults found that the hip circumference divided by height^1.5 minus 18 (the body adiposity index, BAI) was strongly correlated (r = 0.79) with percent body fat determined by dual energy X‐ray absorptiometry. The BAI was proposed as a more accurate index of body fatness than BMI. We examined whether BAI was more strongly related, than was BMI and waist circumference, to skinfold thicknesses and levels of various risk factors for coronary heart disease.

Design and Methods:

Cross‐sectional analyses of adults (n = 14,263 for skinfold thickness; n=6291 for fasting lipid levels) in the National Health and Nutrition Examination Survey (NHANES) III, 1988‐1994.

Results:

As compared with BMI and waist circumference, we found that BAI was less strongly associated with the skinfold sum and with risk factor levels. For example, correlations with the skinfold sum were r = 0.79 (BMI) vs. r = 0.70 (BAI) among men, and r = 0.86 (BMI) vs. r = 0.79 (BAI) among women; p < 0.001 for the difference between each pair of correlations. An overall index of the 7 risk factors was also more strongly associated with BMI and waist circumference than BAI in analyses stratified by sex, race‐ethnicity and age. Multivariable analyses indicated that if BMI was known, BAI provided little additional information on risk factor levels.

Conclusions:

Based on the observed associations with risk factor levels and skinfold thicknesses, we conclude that BAI is unlikely to be a better index of adiposity than BMI.     

Effects of Obesity and Body Fat Distribution on Lipids and Lipoproteins in Nondiabetic American Indians: The Strong Heart Study

Objectives: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Research Methods and Procedures: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high‐density lipoprotei in (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/lipoproteins. Results: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m²) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m²), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = ?0.24, p < 0.001). There was a significant but weak relation with apoAI (r = ?0.14 p < 0.001). Waist circumference was positively related to triglycerides (r = 0.14 p < 0.001) and negatively related to HDL cholesterol (r = ?0.23, p < 0.001) and apoAI (r = ?0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r = 0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = ?0.35, p < 0.001) and apoAI (r = ?0.23, p < 0.001). Triglycerides increased with waist circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist circumference (r = ?0.36 p < 0.001). In both women and men there was an inverted U‐shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (?1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (?0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. Discussion: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles than general obesity in women; both were equally important in men.     

BMI, waist circumference, and incident urinary incontinence in older women

Overall body fat and central adiposity may reflect different mechanisms leading to urinary incontinence (UI). We examined the associations of BMI and waist circumference with incident UI, including the independent associations of BMI and waist circumference with UI type, among women aged 54-79 years in the Nurses' Health Study. Study participants reported their height in 1976 and their weight and waist circumference in 2000. From 2000 to 2002, we identified 6,790 women with incident UI at least monthly among 35,754 women reporting no UI in 2000. Type of incontinence was determined on questionnaires sent to cases with at least weekly incontinence. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression. There were highly significant trends of increasing risk of UI with increasing BMI and waist circumference (P for trend <0.001 for both). Multivariable RRs of developing at least monthly UI were 1.66 (95% CI 1.45-1.91) comparing women with a BMI of > or =35 kg/m(2) to women with BMI 21-22.9 kg/m(2) and 1.72 (95% CI 1.53-1.95) comparing women in extreme quintiles of waist circumference. When BMI and waist circumference were included in models simultaneously, BMI was associated with urge and mixed UI (P for trend 0.003 and 0.03, respectively), but not stress UI (P for trend 0.77). Waist circumference was associated only with stress UI (P for trend <0.001). These results suggest that women who avoid high BMI and waist circumference may have a lower risk of UI development.     

A comparison of adiposity measures as predictors of all-cause mortality: the Melbourne Collaborative Cohort Study

Objective: Our goal was to examine five different measures of adiposity as predictors of all‐cause mortality. Research Methods and Procedures: Subjects were 16,969 men and 24,344 women enrolled between 1990 and 1994 in the Melbourne Collaborative Cohort Study (27 to 75 years of age). There were 2822 deaths over a median follow‐up period of 11 years. BMI, waist circumference, and waist‐to‐hip ratio were obtained from direct anthropometric measurements. Fat mass and percentage fat were estimated by bioelectric impedance analysis. Results: Comparing the top quintile with the second quintile, for men there was an increased risk of between 20% and 30% for all‐cause mortality associated with each of the anthropometric measures. For women, there was an increased risk of 30% (95% confidence interval for hazard ratio, 1.1–1.6) observed for waist circumference and 50% (1.2–1.8) for waist‐to‐hip ratio, but little or no increased risk for BMI, fat mass, and percentage fat. Waist‐to‐hip ratio was positively and monotonically associated with all‐cause mortality for both men and women. There was a linear association between waist circumference and all‐cause mortality for men, whereas a U‐shaped association was observed for women. Discussion: Measures of central adiposity were better predictors of mortality in women in the Melbourne Collaborative Cohort Study compared with measures of overall adiposity. We recommend measuring waist and hip circumferences in population studies investigating the risk of all‐cause mortality associated with obesity. The use of additional measures such as bioelectric impedance is not justified for this outcome.     

Socioeconomic status and adiposity in childhood: a systematic review of cross-sectional studies 1990-2005

Background: Sobal and Stunkard's review (1989) of 34 studies from developed countries published after 1941, found inconsistent relationships between socioeconomic status (SES) and childhood adiposity. Inverse associations (36%), no associations (38%), and positive associations (26%) were found in similar proportions. In view of the trends in pediatric obesity, the relationship between SES and adiposity may have changed. Objective: To describe the cross‐sectional association between SES and adiposity in school‐age children from western developed countries in epidemiological studies since 1989. Methods and Procedures: PubMed database was searched to identify potentially relevant publications. Epidemiological studies from western developed countries presenting cross‐sectional data on the bivariate association between an SES indicator and objectively measured adiposity in childhood (5–18 years), carried out after 1989 were included. SES indicators included parental education, parental occupation, family income, composite SES, and neighborhood SES. Results: Forty‐five studies satisfied the review criteria. SES was inversely associated with adiposity in 19 studies (42%), there was no association in 12 studies (27%), and in 14 studies (31%) there was a mixture of no associations and inverse associations across subgroups. No positive SES‐adiposity associations were seen in unadjusted analyses. With parental education as the SES indicator, inverse associations with adiposity were found in 15 of 20 studies (75%). Discussion: Research carried out within the past 15 years finds that associations between SES and adiposity in children are predominately inverse, and positive associations have all but disappeared. Research is needed to understand the mechanisms through which parental social class influences childhood adiposity.     

Adiposity measures and oxidative stress among police officers

Our objective was to investigate associations between adiposity measures (BMI, waist circumference, waist-to-hip ratio, waist-to-height ratio, and abdominal height) and biomarkers of oxidative stress (glutathione (GSH), GSH peroxidase (GSH-Px), vitamin C, thiobarbituric acid reactive substances (TBARS), and trolox equivalent antioxidant capacity (TEAC)) among police officers. This cross-sectional study included randomly selected police officers (43 policewomen; 67 policemen) from Buffalo, New York. Adiposity measures were performed using standardized methods. Biomarkers were measured on fasting blood specimens. An oxidative stress score (OSS) was created as a composite of the biomarkers. ANOVAs were used to compare mean levels of biomarkers across tertiles of the adiposity measures. Officers were 26- to 61-years old. GSH was inversely associated with waist circumference (trend P = 0.030) and waist-to-hip ratio (trend P = 0.026). GSH-Px was inversely associated with BMI (trend P = 0.004) and with waist-to-height ratio (trend P = 0.017). No associations were observed for TEAC, TBARS, or OSS with any adiposity measure. Significant interactions were observed by physical activity status for GSH with waist circumference and waist-to-hip ratio and for vitamin C with waist circumference, waist-to-hip and waist-to-height ratios. The above associations were inversely related only among officers who reported engaging in physical activity. Inverse associations were observed for BMI and waist circumference with GSH, but only among women; the interaction with gender was significant. Larger indices of adiposity were associated with increased levels of oxidative stress and decreased levels of antioxidant defense.     

The relationship between anthropometric indexes of adiposity and vascular function in the FATE cohort

Objective:

Numerous indexes of adiposity have been proposed and are currently in use in clinical practice and research. However, the correlation of these indexes with measures of vascular health remain poorly defined. This study investigated which measure of adiposity is most strongly associated with endothelial function.

Design and Methods:

Data from the Firefighters And Their Endothelium (FATE) study was used. The relationships between three measures of vascular function: flow‐mediated dilation (FMD), hyperemic velocity time integral (VTI), and hyperemic shear stress (HSS), and five measures of adiposity: BMI, waist circumference (WC), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHtR), and body adiposity index (BAI) were tested. Univariate comparisons were made, and subsequently models adjusted for traditional risk factors were constructed.

Results:

A total of 1,462 male firefighters (mean age 49 ± 9) without cardiovascular disease comprised the study population. No measure of adiposity correlated with FMD; all five measures of adiposity were negatively correlated with VTI and HSS (P values <0.0001), with WHtR most strongly correlated with VTI, and WC most strongly correlated with HSS (both P < 0.05). In models including all five measures of obesity simultaneously, BMI, WC, and WHtR were all predictive of HSS (all P values <0.05), and BMI and WHR were both predictive of VTI (P values <0.05).

Conclusions:

Anthropometric measures of adiposity may help refine estimations of atherosclerotic burden. BMI was most consistently associated with endothelial dysfunction, but measures of adiposity that reflect distribution of mass were additive.     

Stress reactivity and adiposity of youth

Objective: The relationship between stress reactivity and total or central adiposity in children has not been widely studied. Data from two studies were combined to determine the relationship between reactivity to interpersonal stress and the adiposity of children. Research Methods and Procedures: Stress reactivity to an interpersonal stressor (speech) was measured in 36 boys (9.8 ± 1.3 years of age) and 27 girls (9.3 ± 1.3 years of age). Total adiposity (percentage body fat) was estimated from skinfolds and central adiposity from the abdominal girth. Multiple regression was used to establish the associations of change in perceived stress and heart rate reactivity with adiposity. Age, sex, ethnicity, and baseline perceived stress and heart rate served as covariates for total adiposity. Fat mass was included as an additional covariate for the prediction of log abdominal girth (central adiposity). Results: Based on adjusted β‐weights, change in perceived stress (β = 1.13, p ≤ 0.001) and heart rate reactivity (β = 0.14, p ≤ 0.03) independently predicted percentage body fat. Heart rate reactivity (β = 0.002, p ≤ 0.04) independently predicted log abdominal girth. Discussion: Reactivity to psychological stress may initiate the antecedents of cardiovascular disease before adolescence by increasing total and central adiposity. Future studies should determine whether stress reactivity increases the adiposity of youth by increasing their consumption of energy‐dense snack foods and decreasing their willingness to be physically active.     

Gly40Ser Polymorphism of the Glucagon Receptor Gene Is Associated with Central Adiposity in Men

Objective: To study the association between the Gly40Ser polymorphism of the glucagon receptor gene (GCG‐R) and central adiposity. Research Methods and Procedures: Data from 985 working men (The Olivetti Heart Study) examined in 1994 were used in a cross‐sectional design. A complete anthropometry was performed; body mass index and waist circumference were taken as measures of total and central adiposity, respectively. The GCG‐R Gly40Ser polymorphism was characterized. Biochemical variables linked to energy metabolism were measured. Results: The GCG‐R Gly40Ser variant was present in 37 individuals only in heterozygous form and was significantly associated with anthropometric indices of central adiposity, accounting for age and body mass (odds ratio for waist circumference > 94 cm; 95% confidence interval: 3.14, 1.26 to 7.81), whereas no difference between the two groups was found with regard to biochemical indices of insulin resistance or plasma leptin levels. Discussion: The Gly40Ser polymorphism of the GCG‐R gene is associated with central adiposity independently from total body mass in men.     

Total and Regional Fat and Serum Cardiovascular Disease Risk Factors in Lean and Obese Children and Adolescents

Objective: This study was conducted to evaluate the association of total and central adiposity with serum cardiovascular disease (CVD) risk factors in lean and obese Portuguese children and adolescents. Research Methods and Procedures: A total of 87 girls (13.2 ± 1.6 years old, 29.9 ± 6.4% body fat [mean ± SD]) and 72 boys (13.2 ± 1.6 years old, 20.8 ± 9.9% body fat) volunteered for the study. Whole‐body composition and fat distribution, from DXA and anthropometry, and serum lipids, lipoproteins, and apolipoproteins were evaluated. Results: The sum of three trunk skinfolds (STS) was highly correlated with total trunk fat mass measured by DXA (p < 0.001). Body mass index, DXA‐measured percentage of body fat, trunk fat mass, STS, and the waist‐to‐height ratio were generally found to be associated with triacylglycerol, the ratio of total cholesterol (TC) to high density lipoprotein‐cholesterol (HDL‐C), low density lipoprotein‐cholesterol (LDL‐C), and apolipoprotein B levels, (significant age‐adjusted r between 0.16 and 0.27, p < 0.05). Body mass index, STS, and the waist circumference were also associated with HDL‐C (p < 0.05), whereas no body composition variable significantly correlated with TC or apolipoproteins A‐I. The STS was significantly correlated with HDL‐C (p < 0.01), TC/HDL‐C (p < 0.05), and apolipoproteins A‐I (p < 0.05) independently of whole‐body fatness. Obese subjects (n = 73) had higher TC, LDL‐C, TC/HDL‐C, and apolipoprotein B than did non‐obese subjects (n = 86), and significant associations between central adiposity and some lipid variables (triacylglycerol and HDL‐C) were found in obese children and adolescents that were not present in leaner individuals. Discussion: DXA‐ and anthropometry‐based whole‐body and central fat measures are associated with serum CVD risk factors in Portuguese boys and girls. Obese children and adolescents have a poorer lipid profile than do their leaner counterparts. Trunk skinfolds, which are easy to obtain even in large samples, predict CVD risk factors to the same extent as DXA‐based variables, in some cases, independently of total fatness.     

Formalizing the definition of meta‐analysis in Molecular Ecology

Meta‐analysis, the statistical synthesis of pertinent literature to develop evidence‐based conclusions, is relatively new to the field of molecular ecology, with the first meta‐analysis published in the journal Molecular Ecology in 2003 (Slate & Phua 2003). The goal of this article is to formalize the definition of meta‐analysis for the authors, editors, reviewers and readers of Molecular Ecology by completing a review of the meta‐analyses previously published in this journal. We also provide a brief overview of the many components required for meta‐analysis with a more specific discussion of the issues related to the field of molecular ecology, including the use and statistical considerations of Wright's F_ST and its related analogues as effect sizes in meta‐analysis. We performed a literature review to identify articles published as ‘meta‐analyses’ in Molecular Ecology, which were then evaluated by at least two reviewers. We specifically targeted Molecular Ecology publications because as a flagship journal in this field, meta‐analyses published in Molecular Ecology have the potential to set the standard for meta‐analyses in other journals. We found that while many of these reviewed articles were strong meta‐analyses, others failed to follow standard meta‐analytical techniques. One of these unsatisfactory meta‐analyses was in fact a secondary analysis. Other studies attempted meta‐analyses but lacked the fundamental statistics that are considered necessary for an effective and powerful meta‐analysis. By drawing attention to the inconsistency of studies labelled as meta‐analyses, we emphasize the importance of understanding the components of traditional meta‐analyses to fully embrace the strengths of quantitative data synthesis in the field of molecular ecology.     

Associations of Variants in FTO and Near MC4R With Obesity Traits in South Asian Indians

Recent genome‐wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity‐related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity‐ and type 2 diabetes (T2DM)‐related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity‐related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist—hip ratio. Consistent associations were observed for adipose tissue‐specific measurements such as skinfold thickness reinforcing the association with obesity‐related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity‐related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity‐related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian “thin‐fat” phenotype.     

Work stress, obesity and the risk of type 2 diabetes: gender-specific bidirectional effect in the Whitehall II study

Psychosocial work stress has been linked to higher risk of type 2 diabetes (T2DM), with the effect being consistently higher among women than men. Also, work stress has been linked to prospective weight gain among obese men but weight loss among lean men. Here, we aimed to examine the interaction between work stress and obesity in relation to T2DM risk in a gender‐specific manner. We studied 5,568 white middle‐aged men and women in the Whitehall II study, who were free from diabetes at analysis baseline (1993). After 1993, diabetes was ascertained at six consecutive phases by an oral glucose tolerance test supplemented by self‐reports. Cox regression analysis was used to assess the association between job strain (high job demands/low job control) and 18‐year incident T2DM stratifying by BMI (BMI <30 kg/m² vs. BMI ≥30 kg/m²). Overall, work stress was associated with incident T2DM among women (hazard ratio (HR) 1.41: 95% confidence intervals: 1.02; 1.95) but not among men (HR 0.87: 95% confidence interval 0.69; 1.11) (P_INTERACTION = 0.017). Among men, work stress was associated with a lower risk of T2DM in nonobese (HR 0.70: 0.53; 0.93) but not in obese individuals (P_INTERACTION = 0.17). Among women, work stress was associated with higher risk of T2DM in the obese (HR 2.01: 1.06; 3.92) but not in the nonobese (P_INTERACTION = 0.005). Gender and body weight status play a critical role in determining the direction of the association between psychosocial stress and T2DM. The potential effect‐modifying role of gender and obesity should not be ignored by future studies looking at stress‐disease associations.     

Mediating Effects of Inflammatory Biomarkers on Insulin Resistance Associated with Obesity

Objective: Obesity is associated with elevated levels of biomarkers of inflammation and endothelial dysfunction [including C‐reactive protein (CRP), E‐selectin, and intercellular adhesion molecule‐1], as well as insulin resistance (IR) and type 2 diabetes. We tested the hypothesis that these biomarkers mediate associations among obesity, IR, and risk of diabetes. Research Methods and Procedures: We stratified 510 initially non‐diabetic women in the Nurses’ Health Study cohort into four phenotypes above/below median BMI (27 kg/m²) and waist circumference (81 cm): low BMI‐low waist (LBLW; N = 190), low BMI‐high waist (LBHW; N = 74), high BMI‐low waist (HBLW; N = 27), and high BMI‐high waist (HBHW; N = 219). Results: In models assessing associations of weight phenotype with IR [fasting insulin (FI)], adjusted for age and diabetes risk factors, mean FI was higher comparing HBHW women (13.6 μU/mL, p < 0.0001) and LBHW (11.5 μU/mL, p = 0.02) with LBLW women (8.6 μU/mL); HBLW and LBLW women were not significantly different. Differences in FI levels were most strongly attenuated after adjustment for E‐selectin comparing LBHW with LBLW women (11.7 vs. 9.7 μU/mL, p = 0.2). Discussion: In logistic regression models, LBHW predicted diabetes (risk factor‐adjusted relative risk 2.06, 1.05 to 6.40), compared with LBLW, but was no longer significant after adjustment for E‐selectin or CRP. After adjusting for CRP and E‐selectin, only HBHW and E‐selectin were significantly associated with risk of diabetes. In women with central adiposity and low BMI, endothelial dysfunction and inflammation may mediate the relationship among central fat, IR, and incident diabetes.     

Measures of adiposity and cardiovascular disease risk factors

Objective: To determine which of five measures of adiposity maintains the strongest association with cardiovascular disease risk factors. Research Methods and Procedures: A nationally representative sample of 12,608 adult participants of the third National Health and Nutrition Examination Survey were examined. Waist circumference, total body fat, percent body fat, BMI, and skinfold thickness were measured following a standardized protocol. Results: In multivariable adjusted models including waist circumference and BMI as independent variables, waist circumference was a significantly better predictor. The odds ratios (95% confidence intervals) for each standard deviation higher waist circumference and BMI for men were as follows: 1.88 (1.43, 2.48) and 0.99 (0.76, 1.29), respectively, for hypertension; 1.51 (0.87, 2.59) and 1.23 (0.76, 1.99), respectively, for diabetes; and 1.85 (1.48, 2.32) and 1.00 (0.80, 1.24), respectively, for low high‐density lipoprotein‐cholesterol. The analogous odds ratios (95% confidence intervals) for women were as follows: 2.28 (1.74, 3.00) and 0.91 (0.69, 1.19), respectively, for hypertension; 2.72 (1.85, 4.00) and 0.82 (0.55, 1.23), respectively, for diabetes; and 1.90 (1.47, 2.47) and 1.07 (0.83, 1.38), respectively, for low high‐density lipoprotein‐cholesterol. Results were markedly similar for waist circumference in models adjusting for total body fat, percent body fat, and skinfold thickness separately. In contrast, waist circumference was not a significantly better predictor of elevated C‐reactive protein than the other measures of adiposity. Discussion: Waist circumference maintains a stronger association with cardiovascular disease risk factors than other measures of adiposity.