Circulating adiponectin reflects the degree of energy homeostasis and insulin sensitivity of adult individuals. Low abundance of the high molecular mass multimers (HMW), the most active forms mediating the insulin-sensitizing effects of adiponectin, is indicative of impaired metabolic status. The increase in fetal adiponectin HMW compared with adults is a distinctive features of human neonates. In order to further understand the functional properties of adiponectin during fetal life, we have evaluated the associations of adiponectin with insulin sensitivity, body composition and gender. Umbilical cord adiponectin, adiponectin complexes and metabolic parameters were measured at term by elective Cesarean section. The associations between adiponectin, measures of body composition and insulin sensitivity were evaluated in relation to fetal gender in 121 singleton neonates. Higher total adiponectin concentrations in females compared with male fetuses (34.3±9.5 vs 24.9±8.6, p<0.001) were associated with a 3.2-fold greater abundance in circulating HMW complexes (0.20±0.03 vs 0.08±0.03, p<0.001, n=9). Adiponectin was positively correlated with neonatal fat mass (r= 0.27, p< 0.04) and percent body fat in female fetuses (r= 0.28, p<0.03) and with lean mass in males (r= 0.28, p<0.03). There was no significant correlation between cord adiponectin and fasting insulin concentrations or fetal insulin sensitivity as estimated by HOMA-IR. The gender dimorphism for plasma adiponectin concentration and complex distribution first appears in utero. In sharp contrast to the inverse correlation found in adults, the positive relationship between adiponectin and body fat is a specific feature of the fetus.

The incretin hormone glucagon-like peptide-1 (GLP-1) has been implicated in the regulation of appetite by acting as an anorexigenic gut-brain signal. The postprandial release of GLP-1 can be blunted in obese humans and animals. However, it remains unknown whether obesogenic diets with varying fat and carbohydrate content may differentially influence the effectiveness of GLP-1 feedback. To investigate this, male Sprague-Dawley rats were fed a standard (low fat) chow diet, or one of two high-energy diets varying in fat content (45 or 60 kcal%) for 28 weeks. Intake of sucrose and fructose solutions, two commonly added sugars in the Western diet, was then tested in non-deprived rats following administration of the GLP-1 receptor agonist, Exendin-4 (0, 0.5, 1, 2, 3 µg/kg; s.c.). Exendin-4 dose-dependently reduced short (2-hr) sucrose and fructose intake. This effect was significantly attenuated in rats fed more dietary fat despite both diets resulting in obesity. These findings demonstrate that intake of carbohydrates when offered as treats can be regulated by GLP-1 and suggests that dietary fat consumption, rather than extra calories or obesity, may lead to impaired GLP-1 feedback to curb carbohydrate intake. Future studies are warranted to investigate relevance of these observations to human and to elucidate the underlying mechanisms.

Recent studies have demonstrated an important physiologic link between bone and fat. Bone and fat cells arise from the same mesenchymal precursor cell within bone marrow, capable of differentiation into adipocytes or osteoblasts. Increased BMI appears to protect against osteoporosis. However, recent studies have suggested detrimental effects of visceral fat on bone health. Increased visceral fat may also be associated with decreased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels which are important for maintenance of bone homeostasis. The purpose of our study was to assess the relationship between vertebral bone marrow fat and trabecular bone mineral density (BMD), abdominal fat depots, GH and IGF-1 in premenopausal women with obesity. We studied 47 premenopausal women of various BMI (range: 18–41 kg/m2, mean 30 ± 7 kg/m2) who underwent vertebral bone marrow fat measurement with proton magnetic resonance spectroscopy (1H-MRS), body composition, and trabecular BMD measurement with computed tomography (CT), and GH and IGF-1 levels. Women with high visceral fat had higher bone marrow fat than women with low visceral fat. There was a positive correlation between bone marrow fat and visceral fat, independent of BMD. There was an inverse association between vertebral bone marrow fat and trabecular BMD. Vertebral bone marrow fat was also inversely associated with IGF-1, independent of visceral fat. Our study showed that vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 and BMD. This suggests that the detrimental effect of visceral fat on bone health may be mediated in part by IGF-1 as an important regulator of the fat and bone lineage.

The aim of this study was to evaluate psychometric properties and clinical correlates of the Weight Bias Internalization Scale (WBIS) in a sample of obese adolescents seeking bariatric surgery. Sixty five adolescents enrolled in a bariatric surgery program at a large, urban medical center completed psychiatric evaluations, self-report questionnaires including the WBIS and other measures of psychopathology and physical assessments. The WBIS had high internal consistency (Cronbach’s α = .92). As in previous research with adults, the one underlying factor structure was replicated and 10 of the original 11 items were retained. The scale had significant partial correlations with depression (r = .519), anxiety (r = .465), social and behavioral problems (r = .364), quality of life (r = −.480), and eating (r = .579), shape (r = .815), and weight concerns (r = .545), controlling for body mass index. However, WBIS scores did not predict current or past psychiatric diagnosis or treatment or past suicidal ideation. Overall, the WBIS had excellent psychometric properties in a sample of obese treatment-seeking adolescents and correlated significantly with levels of psychopathology. These findings suggest that the WBIS could be a useful tool for healthcare providers to assess internalized weight bias among treatment-seeking obese youth. Assessment of internalized weight bias among this clinical population has the potential to identify adolescents who may benefit from information on coping with weight stigma which in turn can augment weight loss efforts.

The purposes of these studies were to quantify the concentrations of total nitrate and nitrite (NOx−) cyclic guanosine monophosphate (cGMP), and nitrotyrosine over skin surface in normal weight healthy volunteers (n = 64) compared to overweight/obese subjects (n = 54). A semicircular plastic tube was taped to the skin along acupuncture points (acupoints), meridian line without acupoint (MWOP), and nonmeridian control and filled with a 2-Phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl solution for 20 min. The concentrations of NOx−, cGMP, and nitrotyrosine in the samples were quantified in a blinded fashion using chemiluminescence and enzyme-linked immunosorbent assay, respectively. In normal weight healthy volunteers, NOx− and cGMP concentrations were consistently increased over the pericardium meridian (PC) 4–7 compared with nonmeridian areas. NOx− concentration is enhanced over the bladder meridian (BL) 56–57, but cGMP level is similar between the regions. In overweight/obese subjects, NOx− contents were increased or tended to be elevated over PC and BL regions. cGMP is paradoxically decreased over PC acupoints and nonmeridian control on the forearm but the decreases were blunted along BL regions on the leg. Nitrotyrosine concentrations are markedly elevated (five- to sixfold) over both PC and BL in all areas of overweight/obese subjects. This is the first evidence showing that nitrotyrosine level is tremendously elevated over skin accompanied by paradoxical changes in nitric oxide (NO)-cGMP concentrations over PC skin region in overweight/obese subject. The results suggest that NO-related oxidant inflammation is systemically enhanced while cGMP generation is impaired over PC skin region but not over BL region in obesity.

Food intake and body weight are regulated by a complex system of neural and hormonal signals, of which the anorexigenic neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) is central. In this study, rat models of obesity and weight loss intervention were compared with regard to several 5-HT markers. Using receptor autoradiography, brain regional-densities of the serotonin transporter (SERT) and the 5-HT2A and 5-HT4 receptors were measured in (i) selectively bred polygenic diet-induced obese (pgDIO) rats, (ii) outbred DIO rats, and (iii) Roux-en-Y gastric bypass (RYGB)-operated rats. pgDIO rats had higher 5-HT4 and 5-HT2A receptor binding and lower SERT binding when compared to polygenic diet-resistant (pgDR) rats. The most pronounced difference between pgDIO and pgDR rats was observed in the nucleus accumbens shell (NAcS), a brain region regulating reward aspects of feeding. No differences were found in the 5-HT markers between DIO rats, chow-fed control rats, and DIO rats experiencing a weight loss. The 5-HT markers were also similar in RYGB and sham-operated rats except for a downregulation of 5-HT2A receptors in the NAcS. The higher receptor and lower SERT binding in pgDIO as compared to pgDR rats corresponds to what is reported in overweight humans and suggests that the dysfunctions of the 5-HT system associated with overeating or propensity to become overweight are polygenically determined. Our results support that the obesity-prone rat model has high translational value and suggests that susceptibility to develop obesity is associated with changed 5-HT tone in the brain that may also regulate hedonic aspects of feeding.

This study tested the efficacy of two school-based programs for prevention of body weight/fat gain in comparison to a control group, in all participants and in overweight children. The Louisiana (LA) Health study utilized a longitudinal, cluster randomized 3-arm controlled design, with 28 months of follow-up. Children (N=2060; M age = 10.5 years, SD = 1.2) from rural communities in Grades 4 to 6 participated in the study. 17 school clusters (M = 123 children/cluster) were randomly assigned to one of three prevention arms: 1) Primary Prevention (PP), an environmental modification program, 2) Primary + Secondary Prevention (PP+SP), the environmental program with an added classroom and internet education component, or 3) Control (C). Primary outcomes were changes in percent body fat and body mass index z scores. Secondary outcomes were changes in behaviors related to energy balance. Comparisons of PP, PP+SP, and C on changes in body fat and BMI z scores found no differences. PP and PP+SP study arms were combined to create an environmental modification arm (EM). Relative to C, EM decreased body fat for boys (−1.7% ± 0.38% versus −0.14% ± 0.69%) and attenuated fat gain for girls (2.9% ± 0.22% versus 3.93% ± 0.37%), but standardized effect sizes were relatively small (< 0.30). In conclusion, this school-based environmental modification programs had modest beneficial effects on changes in percent body fat. Addition of a classroom/internet program to the environmental program did not enhance weight/fat gain prevention, but did impact physical activity and social support in overweight children.

Obese women are at increased risk of developing and dying from cancer, but are less likely than non-obese women to receive cancer screening examinations. Our qualitative study explores obese women’s barriers to Pap smears and mammograms in greater depth than previous research. We also seek to understand why some obese women undergo screening while others do not. A purposive sample of moderately to severely obese women over age 40 was recruited from community-based organizations, health clinics, and retail establishments. Semi-structured in-depth interviews (N=33) informed by the Theory of Care-Seeking Behavior and three prior focus groups of obese women (N=18) were recorded and transcribed. Qualitative analysis was iterative, using a grounded theory approach involving a series of immersion/crystallization cycles. Participants verified many barriers to cervical and breast cancer screening previously identified in the general population, including fear, modesty, competing demands, and low perceived risk. Participants also highlighted several weight-related barriers, including insensitive comments about weight, and equipment and gowns that could not accommodate them. Comparison of participants who were up-to-date with both Pap smears and mammograms with those not up-to-date with either screening showed no discernable differences in these barriers, however. Instead, we found that the participants who followed through on their cancer screenings may share certain personality traits, such as conscientiousness or self-regulatory ability, that allow them to complete difficult or feared tasks. Our research therefore suggests that personality may act as an important mediator in health behavior, and should be taken into account in future theoretical models and health behavior interventions, particularly for obese women.

Previous studies estimated critical periods of childhood body mass index (BMI) growth and linked these events to adult adiposity and cardiovascular health. We expand upon both results to link childhood BMI growth patterns with adult blood pressure. Data from male and female participants in the Fels Longitudinal Study were used to estimate childhood BMI growth curves, from which we isolate ages of childhood BMI divergence based upon adult BMI and blood pressure measurements. Repeated measure analysis of variances models were used to estimate BMI growth curves from ages 2 to 17.5 based on both adult BMI (< 25 kg/m2 or ≥ 25 kg/m2) and adult blood pressure (< 120 mmHg or ≥ 120 mmHg for systolic blood pressure; < 80 mmHg or ≥ 80 mm Hg for diastolic blood pressure). Participants with lower bodyweight throughout childhood had lower systolic and diastolic blood pressures in early adulthood. Any relationships between childhood adiposity and adult bodyweight and blood pressure disappeared by age 60. These results were independent of adult BMI and were observed in both men and women. Increased adult blood pressure has its genesis in part from increased childhood BMI.

Odds ratios (ORs) are widely used in scientific research to demonstrate associations between outcome variables and covariates (risk factors) of interest and are often described in language suitable for risks or probabilities, but odds and probabilities are related, not equivalent. In situations where the outcome is not rare (e.g., obesity), ORs no longer approximate the relative risk ratio and may be misinterpreted. Our study examines the extent of misinterpretation of ORs in Obesity and International Journal of Obesity. We reviewed all 2010 issues of these journals to identify all articles that presented ORs. Included articles were then primarily reviewed for correct presentation and interpretation of ORs; and secondarily reviewed for article characteristics that may have been associated with how ORs are presented and interpreted. Of the 855 articles examined, 62 (7.3%) presented ORs. ORs were presented incorrectly in 23.2% of these articles. Clinical articles were more likely to present ORs correctly than social science or basic science articles. Studies with outcome variables that had higher relative prevalence were less likely to present ORs correctly. Overall, almost a quarter of the studies presenting ORs in two leading journals on obesity misinterpreted them. Furthermore, even when researchers present ORs correctly, the lay media may misinterpret them as relative risk ratios. Therefore, we suggest that when the magnitude of associations is of interest, researchers should carefully and accurately present interpretable measures of association -- including risk ratios and risk differences -- to minimize confusion and misrepresentation of research results.

In addition to adipose tissue, recent studies suggest that skeletal muscle may also be a source of low grade inflammation, particularly in inactive and/or overweight individuals. The aim of this study was to examine the presence of macrophages in skeletal muscle from obese subjects with type 2 diabetes (T2D) before and after a 9-month exercise program (vs. a non-exercising control group) (Study 1) and in young vs. elderly subjects (Study 2). In both studies, CD68+ macrophages in vastus lateralis biopsies were determined by immunohistochemistry and inflammation gene expression measured. Macrophage content (%) was calculated by the number of macrophages per 100 muscle fibers. In Study 1, we found relatively low numbers (2–3%) of CD68+ macrophages in skeletal muscle in obese T2D subjects (BMI= 37.3 ± 5.2kg/m2), which were unchanged after a 9-month exercise program (P=0.42). Similarly, in Study 2 (BMI=27.1 ± 2.5kg/m2), CD68+ macrophages were relatively low in muscle (4–5%) and were not different between young and elderly individuals (P=0.42). However, elderly subjects had 2-fold higher CD68 and CD206 gene expression (both P<0.002) than young participants. In both studies, CD68+ muscle macrophages were not associated with BMI. In conclusion, we found little evidence of macrophage accumulation in skeletal muscle in obese T2D subjects or in elderly individuals. A 9-month exercise program was not associated with a decrease in macrophage content.

Elia (1992) identified the specific resting metabolic rates (Ki) of major organs and tissues in young adults with normal weight: 200 for liver, 240 for brain, 440 for heart and kidneys, 13 for skeletal muscle, 4.5 for adipose tissue and 12 for residual mass (all units in kcal/kg per day). The aim of the present study was to assess the applicability of Elia’s Ki values for obese adults. A sample of young women (n = 80) was divided into two groups, nonobese (BMI <29.9 kg/m2) and obese (BMI 30.0–43.2 kg/m2). This study was based on the mechanistic model: REE = Σ (Ki × Ti), where REE is whole-body resting energy expenditure measured by indirect calorimetry and Ti is the mass of individual organs and tissues measured by magnetic resonance imaging. For each organ/tissue, the corresponding Elia’s Ki value was analyzed respectively for nonobese and obese groups by using stepwise univariate regression analysis. Elia’s Ki values were within the range of 95% confidence intervals (CIs) in the nonobese group. However, Elia’s Ki values were outside the right boundaries of 95% CIs in the obese group and a corresponding obesity-adjusted coefficient was calculated as 0.98, indicating that Elia’s values overestimate Ki by 2.0% in obese adults. Obesity-adjusted Ki values were 196 for liver, 235 for brain, 431 for heart and kidneys, 12.7 for skeletal muscle, 4.4 for adipose tissue, and 11.8 for residual mass. In conclusion, although Elia’s Ki values were validated in nonobese women, obesity-adjustments are appropriate for application in obese women.

Of the parameters that determine glucose disposal and progression to diabetes in humans: first-phase insulin secretion, glucose effectiveness, insulin sensitivity, and the disposition index, only insulin sensitivity can be reliably measured in conscious mice. To determine the importance of the other parameters in murine glucose homeostasis in lean and obese states, we developed the frequently sampled intravenous glucose tolerance test (FSIVGTT) for use in unhandled mice. We validated the conscious FSIVGTT against the euglycemic clamp for measuring insulin sensitivity in lean and obese mice. Insulin resistant mice had increased first-phase insulin secretion, decreased glucose effectiveness and a reduced disposition index, qualitatively similar to humans. Intriguingly, while insulin secretion explained most of the variation in glucose disposal in lean mice, glucose effectiveness and the disposition index more strongly predicted glucose disposal in obese mice. Disposition index curves identified individual diet-induced obese mice as having compensated or decompensated insulin secretion. Conscious FSIVGTT opens the door to apply mouse genetics to the determinants of in vivo insulin secretion, glucose effectiveness and disposition index, and further validates the mouse as a model of metabolic disease.

Using a micro-PET/CT scanner, we have measured 18F-fluorodeoxyglucose uptake in interscapular brown adipose tissue (iBAT) in C57Bl/6 mice at intervals across a 24-hour light-dark cycle. Our data reveals a strong 24-hour profile of glucose uptake of iBAT, peaking at approximately 9 hours into the light phase of the 12 hour light, 12 hour dark day. BAT is increasingly gaining attention as being involved in metabolic phenotypes and obesity, where BAT, as observed by PET analysis, negatively correlates with obesity and age. Conversely, animals that show perturbations in circadian clocks, behavior and physiology show metabolic phenotypes. The observation of a 24-hour rhythm in glucose uptake in iBAT makes this tissue a candidate site of interaction between metabolic and circadian systems.

Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-hour blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean [SD] age 41 [5] y; BMI 27.4 [2.0] kg/m2) completed two 14-day treatments with hypocaloric diet and 8.5 or 5.5-h nighttime sleep opportunity in random order 7 [3] months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free-fatty acids (FFA), and 24-hour blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 [0.3] BMI units) during each treatment. Bedtime restriction reduced sleep by 131 [30] min/day. Recurrent sleep curtailment decreased 24-hour serum insulin concentrations (i.e. enhanced 24-hour insulin economy) without changes in oral glucose tolerance and 24-hour glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA which suppressed normally following glucose ingestion, and lower total and LDL cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-hour insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability.

Previous studies have yielded inconsistent results in documenting the association between key dietary factors and adolescent weight change over time. The purpose of this study was to examine the extent to which changes in adolescent sugar-sweetened beverage, diet soda, breakfast and fast food consumption were associated with changes in BMI and percent body fat (PBF), both cross-sectionally and longitudinally. Our sample included 693 Minnesota adolescents followed over two years. Adjusting for physical activity, puberty, race, socio-economic status, age, and total energy intake, cross-sectional findings indicated that for both males and females, diet soda consumption was significantly and positively associated with BMI and PBF, and breakfast intake was significantly and negatively associated with BMI and PBF among girls. In longitudinal analyses, however, there were no significant associations after adjusting for the number of tests performed. This study adds to previous research through its methodological strengths, including adjustment for physical activity and energy intake assessed using state-of-the-art methods (i.e., accelerometers and 24-hour dietary recalls), as well as its evaluation of both BMI and PBF. Additional research is needed to better understand the complex constellation of factors that contribute to adolescent weight gain over time.

Low 25-hydroxyvitamin D (25[OH]D) and adiponectin levels are both associated with obesity and cardiovascular disease. Cross-sectional studies have suggested that 25(OH)D concentrations are positively associated with adiponectin, and that this relation may strengthen with increasing BMI. However, these studies had small samples sizes and did not account for many known confounders of adiponectin levels. We evaluated whether 25(OH)D was independently associated with circulating adiponectin in two large populations, and whether BMI modified this relationship. Cross-sectional analyses were performed on 1206 women from the Nurses’ Health Study I and 439 men from the Health Professionals Follow-Up Study. Multivariable linear regression was used to analyze the independent association between 25(OH)D and adiponectin after controlling for potential confounders. Effect modification by BMI was examined by creating interaction terms between vitamin D and BMI. 25(OH)D concentrations were positively associated with circulating adiponectin in univariate analyses, and also independently associated with adiponectin after multivariable adjustments in both populations (women: β=0.06, P<0.001; men: β=0.07, P<0.05). BMI did not significantly modify the relation between 25(OH)D and adiponectin in either population. Higher 25(OH)D concentrations were independently associated with higher adiponectin concentrations in large populations of women and men. Since lower levels of 25(OH)D and adiponectin are associated with higher cardio-metabolic risk, assessing the effect of vitamin D supplementation on adiponectin levels is warranted.

Variation in anthropometric measurements due to sexual dimorphism can be the result of genotype by sex interactions (G×S). The purpose of this study was to examine the sex-specific genetic architecture in anthropometric measurements in Alaskan Eskimos from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Maximum likelihood based variance components decomposition methods, implemented in SOLAR, were used for GxS analyses. Anthropometric measurements included BMI, waist circumference (WC), waist/height ratio, percent body fat (%BF) and subscapular and triceps skinfolds. Except for WC, mean values of all phenotypes were significantly different in men and women (p < 0.05). All anthropometric measures were significantly heritable (p< 0.001). In a preliminary analysis not allowing for G×S interaction, evidence of linkage was detected between markers D19S414 and D19S220 on chromosome 19 for WC (LOD = 3.5), %BF (LOD = 1.7), BMI (LOD = 2.4), WHtR (LOD = 2.5), subscapular (LOD = 2.1) and triceps skinfolds (LOD = 1.9). In subsequent analyses which allowed for G×S interaction, linkage was again found between these traits and the same two markers on chromosome 19 with significantly improved LOD scores for: WC (LOD = 4.5), %BF (LOD = 3.8), BMI (LOD = 3.5), waist/height ratio (LOD = 3.2), subscapular (LOD = 3.0) and triceps skinfolds (LOD = 2.9). These results support evidence of a G×S interaction in the expression of genetic effects resulting in sexual dimorphism in anthropometric phenotypes and identify the chromosome 19q12-13 region as important for adiposity-related traits in Alaskan Eskimos.

Clinician counseling is a catalyst for lifestyle modification in obesity. Unfortunately, clinicians do not appropriately counsel all obese patients about lifestyle modification. The extent of disparities in clinician counseling is not well understood. Obese participants (BMI ≥30 kg/m2, N = 2097) in the Dallas Heart Study (DHS), a probability-based sample of Dallas County residents ages 18–65, were surveyed regarding health-care utilization and lifestyle counseling over the year prior to DHS enrollment. Health-care utilization and counseling were compared between obese participants across three categories based on the presence of 0, 1, or 2+ of the following cardiovascular (CV) risk factors: hypertension, hypercholesterolemia, or diabetes. Logistic regression modeling was used to determine likelihood of counseling in those with 0 vs. 1+ CV risk factors, stratified by race, adjusting for age, sex, insurance status, and education. Among obese subjects who sought medical care, those with 0 CV risk factors, compared to those with 1 or 2+ CV risk factors, were less likely to report counseling about losing weight (41% vs. 67% vs. 87%, P trend <0.001), dietary changes (44% vs. 71% vs. 85%, P trend <0.001), and physical activity (46% vs. 71% vs. 86%, P trend <0.001). Blacks and Hispanics without CV risk factors had a lower odds of receiving counseling than whites without risk factors on weight loss (adjusted odds ratio (OR), 95% confidence interval (CI) for nonwhites 0.19, [0.13–0.28], whites 0.48, [0.26–0.87]); dietary changes (nonwhites 0.19, [0.13–0.27], whites 0.37, [0.21–0.64]); and physical activity (nonwhites 0.22, [0.16–0.32], whites 0.32, [0.18–0.57]). Lifestyle counseling rates by clinicians are suboptimal among obese patients without CV risk factors, especially blacks and Hispanics. Systematic education about and application of lifestyle interventions could capitalize on opportunities for primary CV risk prevention.

Although Native Hawaiians and Pacific Islanders exhibit the highest rates of obesity and associated chronic diseases of any racial/ethnic group, they remain vastly underrepresented in health research. In a cross-sectional survey of college students (N = 402) we examined body mass index (BMI) and health outcomes in an ethnoracially diverse rural sample of Native Hawaiian/Pacific Islanders (25.1%), Asian-Americans (39.8%) and European Americans (35.1%). Measures assessed BMI, health status, health behaviors, frequency of exercise, and symptoms of psychiatric disorders (i.e., depression, anxiety, posttraumatic stress, and substance abuse and dependence). Regression analyses revealed that an overall model of five predictors (gender, race, regular exercise, difficulty sleeping, and anxiety) was significantly associated with obesity (p<0.001) and correctly classified 84.2% of cases. 30.7% of Native Hawaiians/Pacific Islanders were obese as compared to 9.2% of European Americans and 10.6% of Asian Americans. These findings suggest that Native Hawaiian/ Pacific Islanders are at high risk for obesity and associated medical comorbidities, but that regular physical activity may ameliorate this risk. Further, these results support the consideration of Native Hawaiians/Pacific Islanders as a distinct racial/ethnic subgroup separate from other Asian populations.

Polycystic ovary syndrome (PCOS) is a complex genetic disease characterized by heritable reproductive and metabolic abnormalities. Genetic variants associated with the reproductive phenotype have been mapped to the fibrillin-3 (FBN3) gene and to a novel transcription factor-7-like 2 (TCF7L2) locus (rs11196236 G). The association of these genetic variants with metabolic phenotypes was investigated in 31 PCOS and 18 control women of European ancestry. The insulinogenic index during an oral glucose tolerance test (I30/G30) and insulin secretion rates at the maximal dose during a graded-glucose infusion (ISRmax) were used as indices of insulin secretion. Endogenous glucose production (EGP) and insulin sensitivity (M/I) were determined during a euglycemic clamp. The disposition index (DI) was calculated using M/I and I30/G30 or ISRmax. Compared with noncarriers (n=10) and control (n=10), M/I was decreased (P=1.1 × 10−5) in heterozygous and homozygous PCOS carriers (n=14) of rs11196236 G and this variant predicted M/I (partial r2=0.34, P=0.005) in a regression analysis. Post-absorptive EGP tended to be higher (P=0.040) in heterozygous and homozygous PCOS carriers of the FBN3-associated allele (n=12), allele 8 of D19S884 (FBN3+), compared to PCOS noncarriers (n=19). PCOS carriers of the rs12255372 T (TCF7L2 Caucasian type 2 diabetes mellitus locus) had no significant associated metabolic phenotypes. We conclude that rs11196236 G TCF7L2 variant is associated with peripheral insulin resistance in PCOS but this effect is not seen in control women. The FBN3 risk allele may be associated with changes in basal glucose homeostasis in PCOS. These findings require replication in additional PCOS cohorts.

We examined the association between sleep duration and body mass index in young adults, and, specifically, in possible gender differences. The population-based sample included 955 young men and 1,051 young women (mean age=25.3 years, SD=1.7) who participated in Project EAT-III (Eating and Activity in Teens and Young Adults). In 2008–2009, study participants completed a survey, on which they reported their weight, height, and typical bed and awakening times. Gender-specific regression models estimated cross-sectional associations between sleep duration and weight status, adjusting for age, race, SES, family structure, depressive symptoms, physical activity, and sedentary and dietary behaviors. In multivariable-adjusted linear regression models, an hour increase in sleep was associated with a −0.38 (−0.70, −0.048) BMI in men. Men who slept <7 hours had a 1.4 unit higher mean BMI (27.9; 95% CI: 26.9, 28.9) than men who slept 7–9 hours/day (26.5; 95% CI: 26.1, 27.0). Prevalence estimates of overweight (BMI≥25) and obesity (BMI≥30) were also inversely associated with sleep duration among men. Sleep duration was not associated with BMI, overweight, or obesity in women. Among women, but not men, there was a statistically significant positive association between trouble falling or staying asleep and mean BMI. Sleep may be an important modifiable risk factor for obesity, particularly in young adult men.

Look AHEAD is a randomized trial determining whether intensive lifestyle intervention (ILI) aimed at long-term weight loss and increased physical fitness reduces cardiovascular morbidity and mortality in overweight and obese individuals with type 2 diabetes compared to control (diabetes support and education, DSE). We investigated the correlates of NT-proBNP, a biomarker associated with heart failure risk, in a subsample from 15 of 16 participating centers and tested the hypothesis that ILI decreased NT-proBNP levels. Baseline and one-year blood samples were assayed for NT-proBNP in a random sample of 1500 without, and all 628 with, self-reported baseline CVD (N=2128). Linear models were used to assess relationships that logtransformed NT-proBNP had with CVD risk factors at baseline and that 1-year changes in NT-proBNP had with intervention assignment. At baseline, the mean (SD) age, BMI, and hemoglobin A1c were 59.6 (6.8) years, 36.0 kg/m2 (5.8), and 7.2% (1.1), respectively. Baseline geometric mean NT-proBNP was not different by condition (ILI 53.3 vs DSE 51.5, p=0.45), was not associated with BMI, and was inversely associated with hemoglobin A1c. At 1 year, ILI participants achieved an average weight loss of 8.3% compared to 0.7% in DSE. At 1 year, NT-proBNP levels increased to a greater extent in the intervention arm (ILI +21.3% vs. DSE +14.2%, p=0.046). The increased NT-proBNP associated with ILI was correlated with changes in A1c, BMI, and body composition. In conclusion, among overweight and obese persons with diabetes, an intensive lifestyle intervention that reduced weight was associated with an increased NT-proBNP.

Circulating adiponectin has been associated with both clinical and subclinical cardiovascular disease (CVD). Variants of the adiponectin gene (ADIPOQ) are associated with clinical CVD, but little is known about associations with subclinical CVD. We studied the association of 11 ADIPOQ SNPs with common and internal carotid intima media thickness (cIMT), presence of coronary artery calcification (CAC), and CAC scores (in those with CAC) in 2847 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were Caucasian (n=712), African-American (n=712), Chinese (n=718), and Hispanic (n=705). All models were adjusted for age, sex, and field site, and stratified by race/ethnic group. African-Americans with genotypes AG/GG of rs2241767 had 36% greater (95% CI (16%, 59%), p=0.0001) CAC prevalence; they also had a larger common cIMT (p=0.0043). Also in African-Americans, genotypes AG/AA of rs1063537 were associated with a 35% (95% CI (14%, 59%), p=0.0005) greater CAC prevalence. Hispanics with the AA genotype of rs11711353 had a 37% (95% CI (14%, 66%), p=0.0011), greater CAC prevalence compared to those with the GG genotype. Additional adjustment for ancestry in African-American and Hispanic participants did not change the results. No single SNP was associated with subclinical CVD phenotypes in Chinese or Caucasian participants. There appears to be an association between ADIPOQ SNPs and subclinical CVD in African-American and Hispanics. Replication as well as assessment of other ADIPOQ SNPs appears warranted.

Obesity is epidemic among adolescents in the United States. We sought to analyze the anthropometric measures of adiposity and fasting indices of insulin resistance, including insulin-like growth factor–binding protein-1 (IGFBP-1), and to provide a clinical estimate of intraperitoneal (IP) fat in obese adolescents (BMI ≥95th percentile), between ages 13 and 17 years. Subjects had baseline testing to determine eligibility for a subsequent randomized, placebo-controlled trial of metformin XR therapy. Anthropometry and dual-energy X-ray absorptiometry (DXA) were used to quantify total body fat while abdominal computed tomography (CT) was used to measure IP (CT-IP) and subcutaneous (CT-SQ) fat. Using anthropometry and fasting laboratory data, we constructed regression models for both CT-IP and CT-SQ. A total of 92 subjects, 33 males, were evaluated. Of the 92 subjects, 19 were black. Fasting insulin concentrations were highly associated with other measures of insulin resistance. Median percent body fat across all subjects, as measured by DXA, was 41%. Using CT measures, 67% of abdominal cross-sectional area was fat, 14% of which was IP fat. In multiple regression analysis, waist circumference (WC) and BMI, jointly and independently, were strongly associated with both CT-IP and CT-SQ fat. BMI and WC explained 62% of variance of CT-SQ fat, but only 26% of variance of CT-IP fat. Adding triglyceride:high-density lipoprotein (TG:HDL) ratio and IGFBP-1 (among nonblacks) to the regression model increased the explained variance for estimating CT-IP fat to 45%. When evaluating the metabolic morbidity of an obese adolescent, a model using fasting IGFBP-1, TG:HDL, BMI, and WC may be worthwhile as an estimate of IP fat.