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Objective: The aim of this study was to quantify the contributions of socioeconomic, psychosocial, behavioral, reproductive, and neighborhood exposures in young adulthood to Black-White differences in incident obesity., Methods: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 4488 Black or White adults aged 18 to 30 years without obesity at baseline (1985-1986) were followed over 30 years. Sex-specific Cox proportional hazard models were used to estimate Black-White differences in incident obesity. Models were adjusted for baseline and time-updated indicators., Results: During follow-up, 1777 participants developed obesity. Black women were 1.87 (95% CI: 1.63-2.13) times more likely and Black men were 1.53 (95% CI: 1.32-1.77) times more likely to develop obesity than their White counterparts after adjusting for age, field center, and baseline BMI. Baseline exposures explained 43% of this difference in women and 52% in men. Time-updated exposures explained more of the racial difference in women but less for men, compared with baseline exposures., Conclusions: Adjusting for these exposures accounted for a substantial but incomplete proportion of racial disparities in incident obesity. Remaining differences may be explained by incomplete capture of the most salient aspects of these exposures or potential variation in the impact of these exposures on obesity by race., (© 2023 The Obesity Society.)

Background Low cardiorespiratory fitness (CRF) and obesity are risk factors for heart failure but their associations with right ventricular (RV) systolic function and pulmonary artery systolic pressure (PASP) are not well understood. Methods and Results Participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study who underwent maximal treadmill testing at baseline and had a follow-up echocardiographic examination at year 25 were included. A subset of participants had repeat CRF and body mass index (BMI) assessment at year 20. The associations of baseline and changes in CRF and BMI on follow-up (baseline to year 20) with RV systolic function parameters (tricuspid annular plane systolic excursion, RV Doppler systolic velocity of the lateral tricuspid annulus), and PASP were assessed using multivariable-adjusted linear regression models. The study included 3433 participants. In adjusted analysis, higher baseline BMI but not CRF was significantly associated with higher PASP. Among RV systolic function parameters, higher baseline CRF and BMI were significantly associated with higher tricuspid annular plane systolic excursion and RV systolic velocity of the lateral tricuspid annulus. In the subgroup of participants with follow-up assessment of CRF or BMI at year 20, less decline in CRF was associated with higher RV systolic velocity of the lateral tricuspid annulus and lower PASP, while greater increase in BMI was significantly associated with higher PASP in middle age. Conclusions Higher CRF in young adulthood and less decline in CRF over time are each significantly associated with better RV systolic function. Higher baseline BMI and greater age-related increases in BMI are each significantly associated with higher PASP in middle age. These findings provide insights into possible mechanisms through which low fitness and obesity may contribute toward risk of heart failure.

Arterial stiffness (AS) and obesity are recognized as important risk factors of cardiovascular disease (CVD). The purpose of this study was to investigate the relationship between AS and obesity. AS was defined as high augmentation index (AIx) and low elasticity (C1, large artery elasticity; C2, small artery elasticity) in participants enrolled in the Multi-Ethnic Study of Atherosclerosis at baseline. We compared AIx, C1, and C2 by body mass index (BMI) (< 25, 25-29.9, 30-39.9, ⩾ 40 kg/m 2 ) and waist-hip ratio (WHR) (< 0.85, 0.85-0.99, ⩾ 1). The obesity-AS association was tested across 10-year age intervals. Among 6177 participants (62 ± 10 years old, 52% female), a significant inverse relationship was observed between obesity and AS. After adjustments for CVD risk factors, participants with a BMI > 40 kg/m 2 had 5.4% lower AIx (mean difference [Δ] = -0.82%; 95% CI: -1.10, -0.53), 15.4% higher C1 (Δ = 1.66 mL/mmHg ×10; 95% CI: 1.00, 2.33), and 40.2% higher C2 (Δ = 1.49 mL/mmHg ×100; 95% CI: 1.15, 1.83) compared to those with a BMI < 25 kg/m 2 (all p for trend < 0.001). Participants with a WHR ⩾ 1 had 5.6% higher C1 (∆ = 0.92 mL/mmHg ×10; 95% CI: 0.47, 1.37) compared to those with a WHR < 0.85. The WHR had a significant interaction with age on AIx and C2, but not with BMI; the inverse relationships of the WHR with AIx and C2 were observed only in participants < 55 years between the normal (WHR < 0.85) and the overweight (0.85 ⩽ WHR < 0.99) groups. Different associations of WHR and BMI with arterial stiffness among older adults should be further investigated.

Background and Objectives: Adult class II/III obesity (BMI ≥ 35 kg/m 2 ) has significant adverse health outcomes. Early prevention and treatment are critical, but prospective childhood risk estimates are lacking. This study aimed to define the prospective risk of adult class II/III obesity, using childhood BMI., Methods: Children ages 3-19 years enrolled in cohorts of the International Childhood Cardiovascular Cohort (i3C) consortium with measured BMI assessments in childhood and adulthood were included. Prospective risk of adult class II/III obesity was modeled based on childhood age, sex, race, and BMI., Results: A total of 12,142 individuals (44% male, 85% white) were assessed at median age 14 [Interquartile range, IQR: 11, 16] and 33 [28, 39] years. Class II/III adult obesity developed in 6% of children with normal weight; 29% of children with overweight; 56% of children with obesity; and 80% of children with severe obesity. However, 38% of the 1440 adults with class II/III obesity (553/1440) were normal weight as children. Prospective risk of adult class II/III obesity varied by age, sex, and race within childhood weight status classifications, and is notably higher for girls, black participants, and those in the United States. The risk of class II/III obesity increased with older adult age., Conclusions: Children with obesity or severe obesity have a substantial risk of adult class II/III obesity, and observed prospective risk estimates are now presented by age, sex, race, and childhood BMI. Clinical monitoring of children's BMI for adult class II/III obesity risk may be especially important for females and black Americans.

Background and Objective: Despite plausible laboratory evidence about harms of endocrine-disrupting chemicals (EDCs), systematic reviews and meta-analyses of epidemiological studies do not consistently find such harms. The purpose of this article was to discuss why solid human evidence on EDCs was unlikely to be obtainable even though they are truely harmful to humans., Results: Indeed, there are insurmountable methodological limitations in human studies. They include unpredictable net effects of diverse EDC mixtures, low reliability of exposure assessment, nonmonotonic dose-response relationships, nonexistence of an unexposed group, and complicated interactions with diet and obesity. The exposome is never free from these methodological issues. Therefore, the most persuasive evidence about human harms of EDCs may be increasing EDC-linked diseases at population levels, but traditional epidemiological studies of EDCs, especially short-lived and widely used EDCs, fail to provide consistent results. Nevertheless, human studies of EDCs with long half-lives, for example, persistent organic pollutants (POPs), are still worthwhile because there are fewer methodological issues. Also, they can play a role as surrogate markers of lipophilic chemical mixtures. Notably, although POPs are well-known EDCs, human findings on POPs cannot be attributed to common hormone-disrupting properties because the net effect of diverse EDC mixtures cannot be reliably predicted even with POPs. Homeostasis disruption through mitochondrial dysfunction may be more relevant to such effects., Conclusion: Logical inference should play a primary role in judging harms of EDCs in humans., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Midlife obesity is associated with increased risk of dementia, whereas late-life obesity is commonly associated with a lower risk of dementia. Although methodologic issues are often discussed in this apparent risk reversal, chronic exposure to low-dose organochlorine pesticides (OCPs), an emerging risk factor for dementia in general populations, may contribute to a direct explanation for these differences. OCPs are strong lipophilic chemicals with very long half-lives (several years), primarily stored in adipose tissue and very slowly released and metabolized over years. As serum concentrations of neurotoxic OCPs strongly correlate with brain OCPs ( r = 0.95), any condition enhancing the release of OCPs from the adipose tissue into circulation would increase the risk of dementia. Increased release of OCPs from adipose tissue typically occurs in (1) dysfunctional adipocytes accompanied by uncontrolled lipolysis and (2) weight loss. Weight gain may help sequester circulating OCPs in adipose tissue. As obesity is the most common reason that adipocytes become dysfunctional, midlife obesity can increase dementia risk through the chronic release of OCPs into circulation. However, late-life obesity potentially decreases dementia risk because weight loss after midlife will increase the release of OCPs while weight gain may actually decrease the release. These countervailing forces may underlie paradoxical associations with dementia of obesity in midlife vs late life which is influenced by weight change after midlife. This hypothesis should be tested in future experimental and human studies on obesity and dementia., (Copyright © 2018 American Academy of Neurology.)

Objective: To examine 25-year trends in weight gain, partitioned by time-related and aging-related changes, during early and middle adulthood., Methods: Coronary Artery Risk Development in Young Adults (CARDIA), a prospective, non-nationally representative cohort study conducted at four urban field centers that began in 1985 to 1986 with 5,109 Black (B) and White (W) men (M) and women (W) aged 18 to 30 years, has followed participants for 25 years (aged 43-55 years in 2010-2011). Time-related and aging-related components of weight change were estimated to construct longitudinal models of linear and nonlinear trends., Results: There were nonlinear trends in time-related weight gain in W, with larger weight gains early that attenuated at subsequent exams. Time-related trends were linear in M. There were nonlinear trends in aging-related weight gain in BM, BW, and WM, with the greatest weight gains at younger ages. Aging-related trends were linear in WW. Participants with overweight or obesity in early adulthood had greater attenuation of aging-related weight gain during middle adulthood., Conclusions: These findings partially support recent surveys indicating slower increases in obesity prevalence in recent years. Findings further suggest that aging-related weight gain is greatest in the 20s and may begin attenuating as early as the mid-30s among some groups., (© 2016 The Obesity Society.)

Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome. We discovered that alterations in a network of coexpressed cholesterol metabolism genes are a signature feature of obesity and inflammatory stress. This network included 11 BMI-associated genes related to sterol uptake (↑LDLR, ↓MYLIP), synthesis (↑SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (↓ABCA1, ABCG1), producing a molecular profile expected to increase intracellular cholesterol. Importantly, these alterations were associated with T2D and coronary artery calcium (CAC), independent from cardiometabolic factors, including serum lipid profiles. This network mediated the associations between obesity and T2D/CAC. Several genes in the network harbored C-phosphorus-G dinucleotides (e.g., ABCG1/cg06500161), which overlapped Encyclopedia of DNA Elements (ENCODE)-annotated regulatory regions and had methylation profiles that mediated the associations between BMI/inflammation and expression of their cognate genes. Taken together with several lines of previous experimental evidence, these data suggest that alterations of the cholesterol metabolism gene network represent a molecular link between obesity/inflammation and T2D/CAC., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance., (© The Author 2015. Published by Oxford University Press.)

Background: Insulin resistance is linked to many human chronic diseases. Paradoxically, however, impaired insulin signaling contributes to longevity in various organisms and is suggested as an adaptive mechanism against external stressors, including obesity. We formulated a novel hypothesis that insulin resistance can be beneficial in obese humans, insofar as it does not cause glucose dysmetabolism., Methods: N = 5,241 participants aged ≥40 with normal fasting glucose were combined across the 1988-1994 and 1999-2004 National Health and Nutrition Examination Survey datasets. Mean follow-up period was 6.6 years. Insulin resistance was measured with homeostasis model assessment (HOMA-IR). Outcomes were all causes (n = 724), cardiovascular diseases (CVD, n = 316), and cancer mortality (n = 190)., Results: Supporting the hypothesis, obese persons with high HOMA-IR showed a decreased risk of total and CVD mortality compared to those with the lowest HOMA-IR. Adjusted hazard ratios were 1.0, 0.8, 0.4, and 0.4 (p(trend) = .02) for all death and 1.0, 0.6, 0.2, and 0.2 (p(trend) < .01) for CVD death. On the other hand, lean persons with high HOMA-IR showed about twice the total and CVD mortality compared to persons with the lowest HOMA-IR (p(trend) < .01, respectively)., Conclusions: Insulin resistance in obese individuals may begin as an adaptive mechanism and can be beneficial if it is not associated with glucose dysmetabolism. In contrast, insulin resistance in lean individuals associated with higher risk of total and CVD mortality. Insulin resistance may be multifaceted and conventional approaches to regard insulin resistance itself as a pathological condition may be reconsidered in this light., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The purpose of this study was to measure the linearity of visceral adipose tissue (VAT) accumulation with measures of total body adiposity to determine whether a threshold exists and to explore the association with cardiometabolic risk factors in adults., Methods: Using a cross-sectional design, data were obtained from 723 adults (324 females) age 19-47 years. Body mass index ranged from 15 to 52 kg/m(2) . Segmented linear regression was used to identify sex-specific percent body fat thresholds at which VAT slope changes. Linear regression measured the association of VAT mass, total fat mass, and subcutaneous fat with cardiometabolic risk factors above and below each threshold., Results: Adiposity thresholds were identified at 23.4% body fat in males and 38.3% body fat in females beyond which the slope of VAT per unit of percent body fat increased to strongly positive. Males and females above these adiposity thresholds had significant dyslipidemia (P<0.001), increased insulin resistance (P<0.001), and higher fat mass across all depots., Conclusions: From these cross-sectional data, the following were inferred: the accumulation of VAT mass is not linear with increasing adiposity; increases in visceral accumulation above threshold are associated with decreased insulin sensitivity and cardiovascular risk in males and females independent of total body fat., (© 2014 The Obesity Society.)

Objectives: The goal of this study was to investigate the relationship of body mass index (BMI) and its 25-year change to left ventricular (LV) structure and function., Background: Longstanding obesity may be associated with clinical cardiac dysfunction and heart failure. Whether obesity relates to cardiac dysfunction during young adulthood and middle age has not been investigated., Methods: The CARDIA (Coronary Artery Risk Development in Young Adult) study enrolled white and black adults ages 18 to 30 years in 1985 to 1986 (Year-0). At Year-25, cardiac function was assessed by conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE). Twenty-five-year change in BMI (classified as low: <27 kg/m(2) and high: ≥27 kg/m(2)) was categorized into 4 groups (Low-Low, High-Low, Low-High, and High-High). Multiple linear regression was used to quantify the association between categorical changes in BMI (Low-Low as reference) with LV structural and functional parameters obtained in middle age, adjusting for baseline and 25-year change in risk factors., Results: The mean BMI was 24.4 kg/m(2) in 3,265 participants included at Year-0. Change in BMI adjusted for risk factors was directly associated with incipient myocardial systolic dysfunction assessed by STE (High-High: β-coefficient = 0.67; Low-High: β-coefficient = 0.35 for longitudinal peak systolic strain) and diastolic dysfunction assessed by TDI (High-High: β-coefficient = -074; Low-High: β-coefficient = -0.45 for e') and STE (High-High: β-coefficient = -0.06 for circumferential early diastolic strain rate). Greater BMI was also significantly associated with increased LV mass/height (High-High: β-coefficient = 26.11; Low-High: β-coefficient = 11.87)., Conclusions: Longstanding obesity from young adulthood to middle age is associated with impaired LV systolic and diastolic function assessed by conventional echocardiography, TDI, and STE in a large biracial cohort of adults age 43 to 55 years., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Persistent organic pollutants (POPs) are lipophilic compounds that travel with lipids and accumulate mainly in adipose tissue. Recent human evidence links low-dose POPs to an increased risk of type 2 diabetes (T2D). Because humans are contaminated by POP mixtures and POPs possibly have nonmonotonic dose-response relations with T2D, critical methodological issues arise in evaluating human findings. This review summarizes epidemiological results on chlorinated POPs and T2D, and relevant experimental evidence. It also discusses how features of POPs can affect inferences in humans. The evidence as a whole suggests that, rather than a few individual POPs, background exposure to POP mixtures-including organochlorine pesticides and polychlorinated biphenyls-can increase T2D risk in humans. Inconsistent statistical significance for individual POPs may arise due to distributional differences in POP mixtures among populations. Differences in the observed shape of the dose-response curves among human studies may reflect an inverted U-shaped association secondary to mitochondrial dysfunction or endocrine disruption. Finally, we examine the relationship between POPs and obesity. There is evidence in animal studies that low-dose POP mixtures are obesogenic. However, relationships between POPs and obesity in humans have been inconsistent. Adipose tissue plays a dual role of promoting T2D and providing a relatively safe place to store POPs. Large prospective studies with serial measurements of a broad range of POPs, adiposity, and clinically relevant biomarkers are needed to disentangle the interrelationships among POPs, obesity, and the development of T2D. Also needed are laboratory experiments that more closely mimic real-world POP doses, mixtures, and exposure duration in humans.

Background: Identifying potentially modifiable risk factors is critically important for reducing the burden of chronic kidney disease. We sought to examine the association of body mass index (BMI) with kidney function decline in a cohort of young adults with preserved glomerular filtration at baseline., Study Design: Longitudinal cohort., Setting & Participants: 2,839 black and white young adults with cystatin C-based estimated glomerular filtration rate (eGFRcys)>90mL/min/1.73m(2) taking part in the year-10 examination (in 1995-1996) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study., Predictor: BMI, categorized as 18.5-24.9 (reference), 25.0-29.9, 30.0-39.9, and ≥40.0kg/m(2)., Outcomes: Trajectory of kidney function decline, rapid decline (>3% per year), and incident eGFRcys <60mL/min/1.73m(2) over 10 years of follow-up., Measurements: GFRcys estimated from the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation for calibrated cystatin C at CARDIA years 10, 15, and 20., Results: At year 10, participants had a mean age of 35.1 years, median eGFRcys of 114mL/min/1.73m(2), and 24.5% had BMI≥30.0kg/m(2). After age 30 years, average eGFRcys was progressively lower with each increment in BMI after adjustment for baseline age, race, sex, hyperlipidemia, smoking status, and physical activity. Higher BMI category was associated with successively higher odds of rapid decline (for 25.0-29.9, 30.0-39.9, and ≥40.0kg/m(2), adjusted ORs were 1.50 [95% CI, 1.21-1.87], 2.01 [95% CI, 1.57-2.87], and 2.57 [95% CI, 1.67-3.94], respectively). 18 participants (0.6%) had incident eGFRcys<60mL/min/1.73m(2). In unadjusted analysis, higher BMI category was associated with incident eGFRcys<60mL/min/1.73m(2) (for 25.0-29.9, 30.0-39.9, and ≥40.0kg/m(2), ORs were 5.17 [95% CI, 1.10-25.38], 7.44 [95% CI, 1.54-35.95], and 5.55 [95% CI, 0.50-61.81], respectively); adjusted associations were no longer significant., Limitations: Inability to describe kidney function before differences by BMI category were already evident. Absence of data for measured GFR or GFR estimated from serum creatinine level., Conclusions: Higher BMI categories are associated with greater declines in kidney function in a cohort of young adults with preserved GFR at baseline. Clinicians should vigilantly monitor overweight and obese patients for evidence of early kidney function decline., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Few studies have examined the relations of adiposity and lifestyle factors in young offspring with their parents as children (parentschild) or at their current age (parentsadult). Therefore, we compared measures of adiposity and lifestyle in parentschild and parentsadult with their offspring., Methods: Two generations (one parent and his/her offspring) participated in this study: 234 parents from a previously established cohort and 382 offspring. Parentsadult and offspring underwent measurements for height, weight, waist circumference, % body fat, visceral fat, and lifestyle habits. Participants were classified as normal weight, overweight, obese based on age-specific BMI criteria. Mixed model linear regression analysis evaluated the associations of adiposity and lifestyle factors of parentschild and parentsadult with that of their offspring, adjusting for age, sex, race, and family membership., Results: The prevalence of obesity was greater among offspring mean age 12.3 years compared to their parentschild mean age 12.6 years (18.4% vs 10.1%, p<0.001) even though hours of television (TV) watching were similar between the two generations as children (p=0.80). Sixty percent of parents (as children and adults) and offspring reported more than 2 hours of TV/day. Offspring of parents who were overweight and obese as children had greater BMI (all p<0.001) than offspring of parents who were normal weight as children. For both parentadult and offspring, adiposity was greater with greater total screen time., Conclusions: Identifying high-risk families is important for early intervention of overweight, especially in children.

Background: Modifiable lifestyle-related factors are associated with risk of coronary heart disease and may also influence kidney disease risk., Study Design: Community-based prospective cohort study., Setting & Participants: 2,354 African American and white participants aged 28-40 years without baseline microalbuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m² recruited from 4 US centers: Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA., Factors: Current smoking, physical activity, fast food habits, obesity, and diet quality, which was based on 8 fundamental components of the Dietary Approaches to Stop Hypertension (DASH) diet, including increased intake of fruits, vegetables, low-fat dairy products, whole grains, and nuts and legumes and reduced intake of sodium, sugar-sweetened beverages, and red and processed meats., Outcomes & Measurements: Spot urine albumin-creatinine ratios were obtained at baseline (1995-1996) and three 5-year follow-up examinations (5, 10, and 15 years' follow-up). Incident microalbuminuria was defined as the presence of age- and sex-adjusted albumin-creatinine ratio ≥25 mg/g at 2 or more of the successive follow-up examinations., Results: During the 15-year follow-up, 77 (3.3%) individuals developed incident microalbuminuria. After multivariable adjustment, poor diet quality (OR, 2.0; 95% CI, 1.1-3.4) and obesity (OR, 1.9; 95% CI, 1.1-3.3) were associated significantly with microalbuminuria; current smoking (OR, 1.6; 95% CI, 0.9-2.8) was associated with microalbuminuria, although the CI crossed 1.0. Neither low physical activity (OR, 1.0; 95% CI, 0.5-1.8) nor fast food consumption (OR, 1.2; 95% CI, 0.7-2.3) was associated with microalbuminuria. Compared with individuals with no unhealthy lifestyle-related factors (poor diet quality, current smoking, and obesity), adjusted odds of incident microalbuminuria were 131%, 273%, and 634% higher for the presence of 1 (OR, 2.3; 95% CI, 1.3-4.3), 2 (OR, 3.7; 95% CI, 1.8-7.7), and 3 (OR, 7.3; 95% CI, 2.1-26.1) unhealthy lifestyle-related factors., Limitations: Self-reported dietary history and physical activity, low number of outcomes., Conclusions: Consuming an unhealthy diet and obesity are associated with incident microalbuminuria., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: This study assessed whether impaired fasting glucose (IFG), insulin resistance, and waist-to-hip ratio (WHR) had effects on cardiac remodeling, independent of obesity, in the MESA (Multi-Ethnic Study of Atherosclerosis) trial., Background: Recent studies have suggested that central obesity and insulin resistance may be primary mediators of obesity-related cardiac remodeling independent of body mass index (BMI)., Methods: We investigated 4,364 subjects without diabetes in the MESA trial. IFG (100 to 125 mg/dl) or insulin resistance (by homeostatic model assessment of insulin resistance [HOMA-IR]) and WHR were used for cardiometabolic phenotyping. Multivariate linear regression analysis was used to determine the effects of the cardiometabolic markers on left ventricular (LV) remodeling, assessed primarily through the LV mass-to-volume ratio obtained by cine cardiac magnetic resonance imaging., Results: Individuals with IFG were more likely to be older and hypertensive, with increased prevalence of cardiometabolic risk factors regardless of BMI. In each quartile of BMI, subjects with above-median HOMA-IR, above-median WHR, or IFG had a higher LV mass-to-volume ratio (p < 0.05 for all). HOMA-IR (p < 0.0001), WHR (p < 0.0001), and the presence of IFG (p = 0.04), but not BMI (p = 0.24), were independently associated with LV mass-to-volume ratio after adjustment for age, sex, hypertension, race, and dyslipidemia., Conclusions: Insulin resistance and WHR were associated with concentric LV remodeling independent of BMI. These results support the emerging hypothesis that the cardiometabolic phenotype, defined by insulin resistance and central obesity, may play a critical role in LV remodeling independently of BMI., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Low levels of osteocalcin (OCN), an osteoblast-specific hormone, have recently been associated with insulin resistance (homeostasis model assessment-insulin resistance (HOMA-IR)) and obesity, particularly in older adults. The aim of this study was to determine whether low levels of OCN would be associated with insulin resistance, obesity, and greater cardiovascular (CV) risk in young adults just emerging from adolescence. Undercarboxylated OCN and carboxylated OCN levels were measured on stored serum samples (total OCN = undercarboxylated OCN + carboxylated OCN) on 137 participants (67 males) at mean age 18.6 years (range 17-22 years). Insulin resistance was measured by hyperinsulinemic-euglycemic clamp (M(lbm)). Multivariable regression analyses with ln(OCN) as the independent variable were adjusted for age, sex, ethnicity, and BMI as indicated. Total OCN was inversely related to BMI, waist circumference, systolic blood pressure (SBP), interleukin (IL)-6, and directly related to M(lbm); only SBP remained significant (with M(lbm) P = 0.0560) after further adjustment for BMI. Carboxylated OCN was inversely related to BMI, waist circumference, SBP, low-density lipoprotein cholesterol (LDL-C), and directly related to adiponectin; SBP and adiponectin remained significant after further adjustment for BMI. There were no significant associations with undercarboxylated OCN. In summary, most associations with OCN were mediated via BMI. However, the significant associations of OCN with SBP, obesity, and adiponectin and borderline with M(lbm), suggest a potential role for OCN in the development of insulin resistance and CV risk that becomes more apparent with aging into older adulthood.

C-reactive Protein (CRP) measurements above 10 mg/L have been conventionally treated as acute inflammation and excluded from epidemiologic studies of chronic inflammation. However, recent evidence suggest that such CRP elevations can be seen even with chronic inflammation. The authors assessed 3,300 participants in The Coronary Artery Risk Development in Young Adults study, who had two or more CRP measurements between 1992/3 and 2005/6 to a) investigate characteristics associated with repeated CRP elevation above 10 mg/L; b) identify subgroups at high risk of repeated elevation; and c) investigate the effect of different CRP thresholds on the probability of an elevation being one-time rather than repeated. 225 participants (6.8%) had one-time and 103 (3.1%) had repeated CRP elevation above 10 mg/L. Repeated elevation was associated with obesity, female gender, low income, and sex hormone use. The probability of an elevation above 10 mg/L being one-time rather than repeated was lowest (51%) in women with body mass index above 31 kg/m(2), compared to 82% in others. These findings suggest that CRP elevations above 10 mg/L in obese women are likely to be from chronic rather than acute inflammation, and that CRP thresholds above 10 mg/L may be warranted to distinguish acute from chronic inflammation in obese women.

Pentadecanoic acid (15:0) and heptadecanoic acid (17:0), the dairy-specific saturated fatty acids have been inversely, while inflammation and oxidative stress have been positively related to the risk of cardiovascular disease (CVD). Both fatty acid metabolism and inflammation and oxidative stress may be influenced by adiposity. In the current cross-sectional analyses among adolescents (mean age 15 years), we determined whether overweight status modified the associations between dairy fatty acids (pentadecanoic acid (15:0) and heptadecanoic acid (17:0)) represented in serum phospholipids (PL) and markers of inflammation and oxidative stress. Six biomarkers for inflammation and oxidative stress were analyzed, including circulating adiponectin, C-reactive protein (CRP), cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and urinary 15-keto-dihydro-PGF2α (15-keto) and 8-iso-PGF2α (F2-iso). Generalized linear regression analyses, adjusted for age, gender, race, tanner score, total energy intake and physical activity, revealed that PL dairy fatty acids were inversely associated with CRP, F2-iso and 15-keto in overweight, but not in normal weight adolescents (all P(interaction) < 0.05). However, higher level of PL dairy fatty acids was associated with lower IL-6 among all adolescents. Further adjustment for dietary intake of calcium, vitamin D, protein, total flavonoids, and ω-3 fatty acids did not materially change the findings. Dairy-specific saturated fats, i.e., 15:0 and 17:0 fatty acids, may contribute to the potential health benefits of dairy products, especially for overweight adolescents.

Lower extremity fat mass (LEFM) has been shown to be favorably associated with glucose metabolism. However, it is not clear whether this relationship is similar across varying levels of obesity. We hypothesized that lower amounts of LEFM is associated with higher insulin resistance (IR) and this association may vary according to weight status. Participants with available measures were examined from the Coronary Artery Risk Development in Young Adults study (CARDIA), a multi-center longitudinal study of the etiology of atherosclerosis in black and white men and women aged 38-50 years old in 2005-2006 (n = 1,579). The homeostasis model assessment of IR (HOMA(IR)) was calculated to estimate IR, regional adiposity was measured using dual energy X-ray absorptiometry (DXA), and weight status was defined according to BMI categories. Obese and overweight participants exhibited higher IR, total fat mass (FM), trunk FM (TFM), and LEFM compared to normal weight participants. After controlling for age, height, race, study center, education, smoking, and cardiorespiratory fitness (CRF), greater LEFM was significantly associated with higher IR only in normal weight men and women. Further adjustment for TFM revealed that lower LEFM was significantly associated with higher IR in overweight and obese men and women and the positive association in normal weight individuals was attenuated. These results suggest that excess adiposity in the lower extremities may attenuate the metabolic risk observed at a given level of abdominal adiposity in overweight and obese individuals. Weight status presents additional complexity since the metabolic influence of adipose tissue may not be homogenous across anatomic regions or level of obesity.

Background: There is emerging evidence that background exposure to persistent organic pollutants (POPs) are important in the development of conditions predisposing to diabetes as well as of type 2 diabetes itself. We recently reported that low dose POPs predicted incident type 2 diabetes in a nested case-control study. The current study examined if low dose POPs predicted future adiposity, dyslipidemia, and insulin resistance among controls without diabetes in that study., Methodology/principal Findings: The 90 controls were diabetes-free during 20 years follow-up. They were a stratified random sample, enriched with overweight and obese persons. POPs measured in 1987-88 (year 2) sera included 8 organochlorine (OC) pesticides, 22 polychlorinated biphenyls (PCBs), and 1 polybrominated biphenyl (PBB). Body mass index (BMI), triglycerides, HDL-cholesterol, LDL-cholesterol, and homeostasis model assessment value for insulin resistance (HOMA-IR) were study outcomes at 2005-06 (year 20). The evolution of study outcomes during 18 years by categories of serum concentrations of POPs at year 2 was evaluated by adjusting for the baseline values of outcomes plus potential confounders. Parallel to prediction of type 2 diabetes, many statistically significant associations of POPs with dysmetabolic conditions appeared at low dose, forming inverted U-shaped dose-response relations. Among OC pesticides, p,p'-DDE most consistently predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 after adjusting for baseline values. Oxychlordane, trans-nonachlor, and hexachlorobenzene also significantly predicted higher triglycerides. Persistent PCBs with ≥7 chlorides predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 with similar dose-response curves., Conclusions/significance: Simultaneous exposure to various POPs in the general population may contribute to development of obesity, dyslipidemia, and insulin resistance, common precursors of type 2 diabetes and cardiovascular diseases. Although obesity is a primary cause of these metabolic abnormalities, POPs exposure may contribute to excess adiposity and other features of dysmetabolism.

Background: Although Methanobacteriales in the gut has recently been linked to obesity, no study has examined the hypothesis that waist circumference, a marker of visceral obesity, are positively associated with Methanobacteriales in the general population. Since Methanobacteriales increase in a petroleum-contaminated environment to biodegrade petroleum as one way of autopurification, we also hypothesized that high body burden of highly lipophilic petroleum-based chemicals like organochlorine pesticides (OCPs) is associated with higher levels of Methanobacteriales in the gut., Methodology/principal Findings: Among 83 Korean women who visited a community health service center for a routine health checkup, quantitative real-time PCR (qPCR) based on 16S rDNA was used to quantify Methanobacteriales in feces. Nine OCPs were measured in both serum and feces of 16 subjects. Methanobacteriales were detected in 32.5% (27/83 women). Both BMI and waist circumference among women with Methanobacteriales were significantly higher than in women without Methanobacteriales (P = 0.04 and P = 0.01, respectively). Also, Methanobacteriales levels in feces were positively associated with BMI and waist circumference (r = +0.23 and P = 0.03 for both). Furthermore, there were significant correlations between feces Methanobacteriales levels and serum concentrations of most OCPs, including with cis-nonachlor (r = +0.53, P<0.05), oxychlordane (r = +0.46, P<0.1), and trans-nonachlor (r = +0.43, P<0.1). Despite high correlations of serum and feces concentrations of most OCPs, feces OCP concentrations were not clearly associated with feces Methanobacteriales levels., Conclusion/significance: In this cross-sectional study, the levels of Methanobacteriales in the human gut were associated with higher body weight and waist circumference. In addition, serum OCP concentrations were positively correlated with levels of Methanobacteriales. There may be a meaningful link among body burden of OCP, Methanobacteriales in the gut, and obesity in the general population.

Rationale: Adipose tissue produces adiponectin, an anti-inflammatory protein. Adiponectin deficiency in mice is associated with abnormal post-natal alveolar development., Objective: We hypothesized that lower serum adiponectin concentrations are associated with lower lung function in humans, independent of obesity. We explored mediation of this association by insulin resistance and systemic inflammation., Methods and Measurements: Spirometry testing was conducted at years 10 and 20 follow-up evaluation visits in 2,056 eligible young adult participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Body mass index, serum adiponectin, serum C-reactive protein (a marker of systemic inflammation), and insulin resistance were assessed at year 15., Main Results: After controlling for body mass index, years 10 and 20 forced vital capacity (FVC) were 81 ml and 82 ml lower respectively (p = 0.004 and 0.01 respectively) in the lowest vs. highest adiponectin quartiles. Similarly, years 10 and 20 forced expiratory volume in one second (FEV1) were 50 ml and 38 ml lower (p = 0.01 and 0.09, respectively) in the lowest vs. highest adiponectin quartiles. These associations were no longer significant after adjustment for insulin resistance and C-reactive protein. Serum adiponectin was not associated with FEV1/FVC or peak FEV1., Conclusions: Independent of obesity, lower serum adiponectin concentrations are associated with lower lung function. The attenuation of this association after adjustment for insulin resistance and systemic inflammation suggests that these covariates are on a causal pathway linking adiponectin and lung function.

Introduction: Circulating oxidized low-density lipoprotein (LDL), a marker of oxidative stress, is associated with obesity, insulin resistance, metabolic syndrome, and cardiovascular disease in adults. However, little is known about its relation to insulin resistance and cardiovascular risk factors in children. The purpose of this study was to assess the relation of oxidative stress, measured by circulating oxidized LDL, with measures of adiposity and insulin resistance in children., Methods: Oxidized LDL, measures of body fatness (body mass index: BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral and subcutaneous fat), insulin resistance with euglycemic insulin clamp (Mlbm), blood pressure, and blood lipids were obtained in 78 children. Oxidized LDL was compared between normal weight children (BMI < 85th percentile) and overweight/obese children (BMI ≥ 85th percentile) and levels were evaluated for associations with body fatness and insulin resistance., Results: Oxidized LDL levels were significantly higher in overweight/obese vs. normal weight children (p < 0.0001). Oxidized LDL was significantly correlated with BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral fat, and abdominal subcutaneous fat (all p-values <0.0001). Moreover, oxidized LDL was negatively correlated with Mlbm, even after adjustment for adiposity (p < 0.01)., Conclusions: Oxidized LDL is significantly associated with adiposity and with insulin resistance, independent of body fatness, in children. Oxidative stress may be independently related to the development of insulin resistance early in life, especially in obese youth., (© 2010 John Wiley & Sons A/S.)

Circulating adiponectin is involved in the atherosclerotic process and has been associated with cardiovascular disease as well as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. The adiponectin gene (ADIPOQ) encodes the circulating protein adiponectin and affects its expression. Only a small proportion of all known ADIPOQ polymorphisms have been investigated in relation to circulating adiponectin concentrations. Using data from 3,355 African-American and white men and women aged 33-45 at the year 15 examination from the Coronary Artery Development in Young Adults (CARDIA) Study the association between 10 single-nucleotide polymorphisms (SNPs) within ADIPOQ and serum adiponectin was examined using linear regression. SNPs were chosen based on a tagSNP approach. Models were stratified by self-reported race to control for population stratification, and Bonferroni corrected for multiple comparisons. ADIPOQ SNPs rs17300539 (P < 0.0001), rs182052 (P = 0.0013), rs822393 (P = 0.0005), rs9882205 (P = 0.0001), and rs3774261 (P = 0.0001) were strongly associated with serum adiponectin concentrations in whites. In general, there was a dose-response relationship of adjusted mean adiponectin concentrations across genotypes. Only one SNP, rs17300539 was marginally associated with serum adiponectin concentrations (P = 0.0087) in African Americans. Significant interactions were found between waist and rs182052 (P = 0.0029) and between rs9882505 and smoking (P = 0.001) in whites. Many ADIPOQ SNPs have not yet been examined, and additional studies are needed to determine whether these may be functional variants.

This study examined prepregnancy cardiometabolic risk factors and gestational diabetes mellitus (GDM) in subsequent pregnancies. The authors selected 1,164 women without diabetes before pregnancy who delivered 1,809 livebirths between 5 consecutive examinations from 1985 to 2006 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The authors measured prepregnancy cardiometabolic risk factors and performed multivariate repeated-measures logistic regression to compute the odds of GDM adjusted for race, age, parity, birth order, and other covariates. Impaired fasting glucose (100-125 vs. <90 mg/dL), elevated fasting insulin (>15-20 and >20 vs. <10 μU/mL), and low levels of high-density lipoprotein cholesterol (<40 vs. >50 mg/dL) before pregnancy were directly associated with GDM: The odds ratios = 4.74 (95% confidence interval (CI): 2.14, 10.51) for fasting glucose, 2.19 (95% CI: 1.15, 4.17) for middle insulin levels and 2.36 (95% CI: 1.20, 4.63) for highest insulin levels, and 3.07 (95% CI: 1.62, 5.84) for low levels of high-density lipoprotein cholesterol among women with a negative family history of diabetes; all P < 0.01. Among overweight women, 26.7% with 1 or more cardiometabolic risk factors developed GDM versus 7.4% with none. Metabolic impairment exists before GDM pregnancy in nondiabetic women. Interconceptual metabolic screening could be included in routine health assessments to identify high-risk women for GDM in a subsequent pregnancy and to potentially minimize fetal exposure to metabolic abnormalities that program future disease.

Diabetes mellitus and hypertension commonly coexist, but the nature of this link is not well understood. The authors tested whether diabetes and higher concentrations of fasting serum glucose and insulin are associated with increased risk of developing incident hypertension in the community-based Multi-Ethnic Study of Atherosclerosis. At baseline, 3,513 participants were free of hypertension, defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive medications to treat high blood pressure. Of these, 965 participants (27%) developed incident hypertension over 4.7 years' median follow-up between 2002 and 2007. Compared with participants with normal baseline fasting glucose, those with impaired fasting glucose and diabetes had adjusted relative risks of hypertension of 1.16 (95% confidence interval (CI): 0.96, 1.40) and 1.41 (95% CI: 1.17, 1.71), respectively (P = 0.0015). The adjusted relative risk of incident hypertension was 1.08 (95% CI: 1.04, 1.13) for each mmol/L higher glucose (P < 0.0001) and 1.15 (95% CI: 1.05, 1.25) for each doubling of insulin (P = 0.0016). Further adjustment for serum cystatin C, urinary albumin/creatinine ratio, and arterial elasticity measured by tonometry substantially reduced the magnitudes of these associations. In conclusion, diabetes and higher concentrations of glucose and insulin may contribute to the development of hypertension, in part through kidney disease and arterial stiffness.

Objective: We characterized the state of the vascular endothelium in pediatric obesity by comparing circulating endothelial cell (CEC) number and activation phenotype in severely obese children to that of normal weight, overweight, and obese children., Study Design: We used immunohistochemical examination of buffy-coat smears to enumerate CEC and immunofluorescence microscopy to quantify activated CEC in 107 children and adolescents. Normal weight (body mass index [BMI]<85th percentile; n=40), overweight (BMI 85th-<95th percentile; n=17), and obese (BMI 95th-<99th percentile; n=23) participants were recruited from a longitudinal study. Severely obese (BMI>or=99th percentile; n=27) participants were recruited from a pediatric obesity clinic. Group means (adiposity; systolic blood pressure [SBP] quartiles) were compared with general linear models, adjusted for sex, age, and race. With Pearson correlations, we characterized relations of CEC with cardiovascular risk factors., Results: Activated CEC increased across BMI groups (P<.002) and SBP quartiles (P<.05). CEC number and activated CEC were highest in the severely obese group. CEC number was significantly associated with SBP, diastolic blood pressure, and triglycerides level. Activated CEC were significantly associated with SBP and high-density lipoprotein cholesterol levels., Conclusions: The vascular endothelium was activated in relation to excess adiposity, particularly in severely obese children, and to elevated SBP in children and adolescents., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: The mechanism for the obesity-asthma association is unknown. This study evaluated the hypothesis that systemic oxidant stress explains this association., Methods: This cross-sectional study used year-20 follow-up evaluation data of 2,865 eligible participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Current asthma was self-reported. Oxidant stress primarily was assessed by plasma F2-isoprostane concentrations. Obesity measures included categories of BMI and dual-energy x-ray absorptiometry-assessed fat mass index (FMI) and lean mass index (LMI). Logistic and linear regressions were used for analyses., Results: Asthma was associated with higher plasma F2-isoprostane concentrations (p = 0.049); however, this association was not significant when adjusted for either gender or BMI. The BMI-asthma association was seen only among women (p = 0.03; gender-specific interaction, p = 0.01), and this association was not explained by plasma F2-isoprostane levels. Similarly, both FMI and LMI were positively associated with asthma in women (p = 0.20 and 0.01, respectively). These associations also were not explained by plasma F2-isoprostane levels. Similar results were obtained when plasma levels of oxidized low-density lipoprotein were used instead of F2-isoprostane levels to study the BMI-asthma association at the year-15 evaluation., Conclusions: Systemic oxidant stress, primarily assessed by plasma F2-isoprostane concentrations, was not independently associated with asthma and, therefore, may not explain the obesity-asthma association in women. The asthma-oxidant stress association is confounded by gender and obesity. This study is limited by the inability to measure airway oxidant stress. It is possible that another (as yet undetermined) measure of systemic oxidant stress may be more relevant in asthma.

Objective: We sought to prospectively examine whether childbearing is associated with higher incidence of the metabolic syndrome (MetS) after delivery among women of reproductive age., Study Design: In 1451 nulliparas who were aged 18-30 years and free of the MetS at baseline (1985-1986) and reexamined up to 4 times during 20 years, we ascertained incident MetS defined by the National Cholesterol Education Program Adult Treatment Panel III criteria among time-dependent interim birth groups by gestational diabetes mellitus (GDM): (0 [referent], 1 non-GDM, 2+ non-GDM, 1+ GDM births). Complementary log-log models estimated relative hazards of the MetS among birth groups adjusted for race, age, and baseline and follow-up covariates., Results: We identified 259 incident MetS cases in 25,246 person-years (10.3/1000 person-years). Compared with 0 births, adjusted relative hazards (95% confidence interval [CI]) were 1.33 (95% CI, 0.93-1.90) for 1 non-GDM, 1.62 (95% CI, 1.16-2.26) for 2+ non-GDM (P trend = .02), and 2.43 (95% CI, 1.53-3.86) for 1+ GDM births., Conclusion: Increasing parity is associated with future development of the MetS independent of prior obesity and pregnancy-related weight gain. Risk varies by GDM status.

Background: Although walking is the most popular leisure-time activity for adults, few long-term, longitudinal studies have examined the association between walking, an affordable and accessible form of physical activity, and weight gain., Objective: The objective was to evaluate the association between changes in leisure-time walking and weight gain over a 15-y period., Design: Prospective data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study of 4,995 men and women aged 18-30 y at baseline (1985-1986) from 4 US cities and reexamined 2, 5, 7, 10, and 15 y later. Sex-stratified, repeated-measures, conditional regression modeling with data from all 6 examination periods (n = 23,633 observations) was used to examine associations between walking and annualized 15-y weight change, with control for 15-y nonwalking physical activity, baseline weight (and their interaction), marital status, education, smoking, calorie intake, and baseline age, race, and field center., Results: Mean (+/- SE) baseline weights were 77.0 +/- 0.3 kg (men) and 66.2 +/- 0.3 kg (women), weight gain was approximately 1 kg/y, and the mean duration of walking at baseline was <15 min/d. After accounting for nonwalking physical activity, calorie intake, and other covariates, we found a substantial association between walking and annualized weight change; the greatest association was for those with a larger baseline weight. For example, for women at the 75th percentile of baseline weight, 0.5 h of walking/d was associated with 8 kg less weight gain over 15 y compared with women with no leisure time walking., Conclusion: Walking throughout adulthood may attenuate the long-term weight gain that occurs in most adults.

This study investigated associations between neighborhood physical and social environments and body mass index in 2,865 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) aged 45-84 years and residing in Maryland, New York, and North Carolina. Neighborhood (census tract) environments were measured in non-MESA participants residing in MESA neighborhoods (2000-2002). The neighborhood physical environment score combined measures of a better walking environment and greater availability of healthy foods. The neighborhood social environment score combined measures of greater aesthetic quality, safety, and social cohesion and less violent crime. Marginal maximum likelihood was used to estimate associations between neighborhood environments and body mass index (kg/m(2)) before and after adjustment for individual-level covariates. MESA residents of neighborhoods with better physical environments had lower body mass index (mean difference per standard deviation higher neighborhood measure = -2.38 (95% confidence interval (CI): -3.38, -1.38) kg/m(2) for women and -1.20 (95% CI: -1.84, -0.57) kg/m(2) for men), independent of age, race/ethnicity, education, and income. Attenuation of these associations after adjustment for diet and physical activity suggests a mediating role of these behaviors. In men, the mean body mass index was higher in areas with better social environments (mean difference = 0.52 (95% CI: 0.07, 0.97) kg/m(2)). Improvement in the neighborhood physical environment should be considered for its contribution to reducing obesity.

We examined the relationship between whole grain intake and obesity, insulin resistance, inflammation, diabetes and subclinical CVD using baseline data from the Multi-Ethnic Study of Atherosclerosis. Whole grain intake was measured by a 127-item FFQ in 5496 men and women free of CHD and previously known diabetes. Mean whole grain intake was 0.5 (sd 0.5) servings per d; biochemical measures reflect fasting levels. After adjustment for demographic and health behaviour variables, mean differences for the highest quintile of whole grain intake minus the lowest quintile of intake were 0.6 kg/m2 for BMI, 0.36 mg/l for C-reactive protein, 0.82 micromol/l for homocysteine, 0.15 mU/l*mmol/l for homeostasis model assessment (HOMA), 0.48 mU/l for serum insulin, 2.0 mg/dl for glucose and 5.7 % for prevalence of newly diagnosed impaired fasting glucose (glucose >or= 100 mg/dl or diabetes medication). These differences represent 11-13 % of a standard deviation of BMI, HOMA, glucose and impaired fasting glucose, but 23 %, 52 % and 80 % of a standard deviation of homocysteine, C-reactive protein and insulin, respectively. An inverse association between whole grains and urine albumin excretion was suggested but retained statistical significance after adjustment only in Chinese and Hispanic participants. No associations were observed between whole grain intake and two subclinical disease measures: carotid intima-media thickness and coronary artery calcification. Concordant with previous research, whole grain intake was inversely associated with obesity, insulin resistance, inflammation and elevated fasting glucose or newly diagnosed diabetes. Counter to hypothesis, however, whole grain intake was unrelated to subclinical CVD.

Background: Some studies have found an association of obesity with type 2 diabetes only among individuals with high normal serum gamma-glutamyltransferase (GGT) activity, not in those with low serum GGT. If this interaction reflected pathophysiology, it would have scientific and clinical importance. The findings failed to reach statistical significance, however, and no articles have focused on the topic. We investigated possible interactions between serum GGT and body mass index (BMI) and their effects on the risk of prevalent type 2 diabetes and homeostasis model assessment (HOMA) insulin resistance., Methods: We analyzed 4011 adults > or =40 years old who participated in the 3rd US National Health and Nutrition Examination Survey., Results: BMI was associated with prevalent diabetes only among persons with high normal serum GGT activity (P for interaction = 0.002). In the highest serum GGT quartile, adjusted odds ratios for BMI 25-29.9, 30-34.5, and > or =35 kg/m(2) compared with BMI<25 kg/m(2) were 3.1, 5.1, and 6.2, respectively (P for trend <0.001). In the lowest serum GGT quartile, BMI was not associated with diabetes; corresponding adjusted odds ratios were 1.0, 0.9, 1.8, and 0.8 (P for trend = 0.551). After prevalent diabetes was excluded, there was a parallel interaction with HOMA levels (P for interaction <0.001)., Conclusions: BMI was not associated with prevalent type 2 diabetes when GGT was low normal, suggesting that obesity itself may not be a sufficient risk factor for type 2 diabetes. Practically, this interaction can be useful in clinical settings to identify individuals at high risk for type 2 diabetes.

Background: Away-from-home food consumption has rapidly increased, though little is known about the independent associations of restaurant food and fast food intake with body mass index (BMI) and BMI change., Objective: The aim was to compare the associations of restaurant food and fast food consumption with current and 3-y changes in BMI., Design: Multivariate linear regression models, with control for demographic and lifestyle factors, were used to examine cross-sectional and longitudinal associations of away-from-home eating with BMI by using data from subjects of the Coronary Artery Risk Development in Young Adults Study (n = 3394) obtained at exam years 7 (1992-1993) and 10 (1995-1996)., Results: Forty percent of the sample increased their weekly consumption of restaurant or fast food, though mean (+/-SD) changes were -0.16 +/- 2.39 times/wk (P = 0.0001) and -0.56 +/- 3.04 times/wk (P < 0.0001), respectively. Cross-sectionally, fast food, but not restaurant food, consumption was positively associated with BMI. Similarly, higher consumption of fast food at year 7 was associated with a 0.16-unit higher BMI at year 10. After adjustment for baseline away-from-home eating, increased consumption of fast food only (beta: 0.20; 95% CI: 0.01, 0.39) and of both restaurant food and fast food (beta: 0.29; 95% CI: 0.06, 0.51) were positively associated with BMI change, though the estimates were not significantly different (P = 0.47). Increased consumption of restaurant food only was unrelated to BMI change (beta: -0.01; 95% CI: -0.21, 0.19), which differed significantly (P = 0.014) from the estimate for an increase in both restaurant food and fast food intake., Conclusions: We found differential effects of restaurant food and fast food intakes on BMI, although the observed differences were not always statistically significant. More research is needed to determine whether the differential effects are related to consumer characteristics or the food itself.

Body mass index, waist circumference, and waist/hip ratio have been shown to be associated with type 2 diabetes. From the clinical perspective, central obesity (approximated by waist circumference or waist/hip ratio) is known to generate diabetogenic substances and should therefore be more informative than general obesity (body mass index). Because of their high correlation, from the statistical perspective, body mass index and waist circumference are unlikely to yield different answers. To compare associations of diabetes incidence with general and central obesity indicators, the authors conducted a meta-analysis based on published studies from 1966 to 2004 retrieved from a PubMed search. The analysis was performed with 32 studies out of 432 publications initially identified. Measures of association were transformed to log relative risks per standard deviation (pooled across all studies) increase in the obesity indicator and pooled using random effects models. The pooled relative risks for incident diabetes were 1.87 (95% confidence interval (CI): 1.67, 2.10), 1.87 (95% CI: 1.58, 2.20), and 1.88 (95% CI: 1.61, 2.19) per standard deviation of body mass index, waist circumference, and waist/hip ratio, respectively, demonstrating that these three obesity indicators have similar associations with incident diabetes. Although the clinical perspective focusing on central obesity is appealing, further research is needed to determine the usefulness of waist circumference or waist/hip ratio over body mass index.

This study evaluated the influence of adiposity on the progression of left ventricular (LV) mass from childhood to adulthood and the relation of LV mass to insulin resistance in young adulthood. One hundred thirty-two healthy children recruited into a longitudinal study at a mean age of 13 years and reevaluated at 27 years, at which time insulin resistance studies were also performed, were studied. Echocardiographic assessment of LV mass was made and indexed for height. Body mass index (BMI) at 13 years was highly correlated with BMI at 27 years, as was LV mass index at 13 and 27 years. The cross-sectional correlation of LV mass index and BMI at 13 years (r = 0.38, p < 0.0001) had strengthened considerably by 27 years (r = 0.55, p < 0.0001). A BMI increase > or = 5.5 kg/m2 from 13 to 27 years was associated with a significantly greater increase in the LV mass index (p < 0.0001) than a BMI change < 5.5 kg/m2, and this relation was similar in children who were thin and heavy at baseline. In young adulthood, the relation of LV mass index to lean mass was weaker than that of LV mass index to fat mass. The association of LV mass with insulin resistance was dependent on adiposity. In conclusion, adiposity and LV mass are related in childhood, and this association tracks and becomes stronger in young adulthood. Moreover, the increase in LV mass from childhood to young adulthood is related to the degree of increase in BMI, independent of BMI at 13 years, suggesting that an excessive increase in LV mass could be limited by controlling gain in body fat during adolescence.

Serum gamma-glutamyltransferase (GGT) concentration within its normal range has emerged as an important predictor in the pathogenesis of diabetes. We studied serum GGT as a predictor of type 2 diabetes incidence and a possible interaction between obesity and GGT on the development of type 2 diabetes in men and women. A prospective cohort study of 20,158 Finnish men and women aged 25-64 yr who participated in cardiovascular risk-factor surveys carried out in four areas during 10 yr. The average follow-up time was 12.7 yr, and there were 388 incident diabetes cases. Serum GGT cut points were at the 25th, 50th, 75th, and 90th percentiles. Initiation of new diabetes medication defined incidence cases. After adjustment for known risk factors of type 2 diabetes, relative risks for incident diabetes across GGT categories were 1.0, 1.2, 2.3, 3.1, and 3.9 among men and 1.0, 0.8, 1.7, 3.5, and 6.4 among women (P for trend < 0.01, respectively). Body mass index appeared to be more strongly associated with type 2 diabetes in both men and women over age 50 yr with GGT median or greater, compared with subjects with GGT less than median. In conclusion, in women as well as men, serum GGT level within its normal range predicted type 2 diabetes and may modify the well-known association between body mass index and type 2 diabetes.

Objective: This paper describes the development of an after-school obesity-prevention program for African-American girls, and presents findings from a 12-week pilot trial conducted by the University of Minnesota. This study was part of the GEMS project, created to test interventions designed to reduce excess weight gain in African-American girls., Design: Two-arm parallel group, randomized controlled trial. Measures were taken at baseline and at 12 weeks follow up., Setting: An after-school community program., Participants: Fifty-four African-American girls, 8- to 10-years of age, and their parents/caregivers., Intervention: The after-school intervention was conducted twice a week for 12 weeks, and focused on increasing physical activity and healthy eating. A family component was also included. Girls in the control group received a program over 12 weeks unrelated to nutrition and physical activity., Outcomes: Measures included height and weight (body mass index), percent body fat (DEXA), physical activity, assessed using a CSA accelerometer and self-report, two 24-hour dietary recalls, and psycho-social and demographic variables. Parental data included demographic and psycho-social characteristics, and dietary measures. Additionally, process evaluation data on the intervention were collected., Results: Recruitment goals were met. After adjustment for baseline level, follow-up BMI did not differ between the treatment groups, an expected finding, given that this was a pilot study. At 12 weeks follow up, differences between the intervention and control groups were in the hypothesized direction of change for most variables, among both the girls and their parents. Process evaluation results demonstrated that the program was well attended, and well received, by girls and parents., Conclusions: An after-school obesity prevention program for low-income African-American girls is a promising model for future efforts.

Objectives: To examine the relation of leptin to insulin resistance, as measured by euglycemic insulin clamp, and insulin resistance syndrome factors in thin and heavy children., Research Methods and Procedures: Anthropometrics, insulin, blood pressure, and leptin were measured in 342 11- to 14-year-old children (189 boys, 153 girls, 272 white, 70 black). Insulin sensitivity (M) was determined by milligrams glucose uptake per kilogram per minute and expressed as M/lean body mass (Mlbm). Children were divided by median BMI (boys = 20.5 kg/m(2); girls = 21.4 kg/m(2)) into below-median (thin) and above-median (heavy) groups. Correlation coefficients between log-leptin and components of insulin resistance syndrome were adjusted for Tanner stage, gender, and race., Results: BMI was related to leptin in boys (r = 0.70, p < 0.001) and girls (r = 0.75, p < 0.001). Leptin was higher in girls than boys (32.6 vs. 12.3 ng/mL, p = 0.0001). Leptin levels increased in girls and decreased in boys during puberty, paralleling the changes in body fat. Leptin was significantly correlated with insulin, Mlbm, triglycerides, and blood pressure in heavy children and only with insulin in thin children. After adjustment for body fat, the correlations remained significant for insulin and Mlbm in heavy children and with insulin in thin children., Discussion: Significant associations were found between leptin and insulin resistance in children, and these associations were attenuated by adjustment for adiposity. These findings at age 13 likely have long-term consequences in the development of the obesity-insulin resistance-related cardiovascular risk profile.

The objective was to describe trends in cardiovascular risk factors between 1980-1982 and 1995-1997 in metropolitan Minneapolis-St. Paul, Minnesota. Four population-based surveys of 4,000-6,000 adults aged 25-74 years were conducted in 1980-1982, 1985-1987, 1990-1992, and 1995-1997 using consistent sampling strategies and protocols. The authors completed interviews and examinations to characterize cardiovascular risk factors. Blood samples were drawn and assayed for several analytes including total cholesterol. Although total cholesterol decreased 7-9 mg/dl during the 1980s, no further reduction was noted between 1990-1992 and 1995-1997. Hypercholesterolemia prevalence (total cholesterol of >240 mg/dl and/or use of lipid-lowering medication) fell between 1980-1982 and 1990-1992 but increased thereafter. Current cigarette smoking, systolic blood pressure, and hypertension prevalence decreased significantly between 1980-1982 and 1995-1997. Body mass index increased substantially across the four surveys. Although there was little change in the mean leisure-time physical activity, the proportion of the population not engaging in regular exercise increased between 1990-1992 and 1995-1997. Dietary fat decreased consistently from 1980-1982 to 1995-1997, while overall caloric intake rose 8% in women but not men. To conclude, the favorable trends in hypertension, cigarette smoking, and dietary fat consumption observed in Minneapolis-St. Paul from 1980-1982 to 1995-1997 were paralleled by less favorable recent trends in total cholesterol, hypercholesterolemia, adiposity, and physical activity.

Both intake of whole grain and higher levels of serum enterolactone have been related to reduced risk for CHD and some cancers. Because lignans are prevalent in the outer layers of grains, these findings may be related. We carried out a crossover feeding study in which overweight, hyperinsulinaemic, non-diabetic men (n 5) and women (n 6) ate, in random order, wholegrain foods or refined-grain foods in a diet with 30 % energy from fat. The dominant whole grain was wheat, followed by oats and rice. All food was supplied by the investigators and each diet lasted for 6 weeks, with an intervening washout period of 6-9 weeks. Serum enterolactone concentrations were higher when eating the wholegrain than the refined-grain diet by 6.2 (within person SE 1.7) nmol/l (P=0.0008). Most of the increase in serum enterolactone when eating the wholegrain diet occurred within 2 weeks, though the serum enterolactone difference between wholegrain and refined-grain diets continued to increase through 6 weeks. Serum enterolactone concentrations can be raised by eating a diet rich in whole grains.

Background: Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of type 2 diabetes and heart disease., Objective: We tested the hypothesis that whole-grain consumption improves insulin sensitivity in overweight and obese adults., Design: This controlled experiment compared insulin sensitivity between diets (55% carbohydrate, 30% fat) including 6-10 servings/d of breakfast cereal, bread, rice, pasta, muffins, cookies, and snacks of either whole or refined grains. Total energy needs were estimated to maintain body weight. Eleven overweight or obese [body mass index (in kg/m(2)): 27-36] hyperinsulinemic adults aged 25-56 y participated in a randomized crossover design. At the end of each 6-wk diet period, the subjects consumed 355 mL (12 oz) of a liquid mixed meal, and blood samples were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered., Results: Fasting insulin was 10% lower during consumption of the whole-grain than during consumption of the refined-grain diet (mean difference: -15 +/- 5.5 pmol/L; P = 0.03). After the whole-grain diet, the area under the 2-h insulin curve tended to be lower (-8832 pmol.min/L; 95% CI: -18720, 1062) than after the refined-grain diet. The rate of glucose infusion during the final 30 min of the clamp test was higher after the whole-grain diet (0.07 x 10(-4) mmol.kg(-1).min(-1) per pmol/L; 95% CI: 0.003 x 10(-4), 0.144 x 10(-4))., Conclusion: Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease.

Context: Components of the insulin resistance syndrome (IRS), including obesity, glucose intolerance, hypertension, and dyslipidemia, are major risk factors for type 2 diabetes and heart disease. Although diet has been postulated to influence IRS, the independent effects of dairy consumption on development of this syndrome have not been investigated., Objective: To examine associations between dairy intake and incidence of IRS, adjusting for confounding lifestyle and dietary factors., Design: The Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based prospective study., Setting and Participants: General community sample from 4 US metropolitan areas of 3157 black and white adults aged 18 to 30 years who were followed up from 1985-1986 to 1995-1996., Main Outcome Measure: Ten-year cumulative incidence of IRS and its association with dairy consumption, measured by diet history interview., Results: Dairy consumption was inversely associated with the incidence of all IRS components among individuals who were overweight (body mass index > or =25 kg/m(2)) at baseline but not among leaner individuals (body mass index < 25 kg/m(2)). The adjusted odds of developing IRS (2 or more components) were 72% lower (odds ratio, 0.28; 95% confidence interval, 0.14-0.58) among overweight individuals in the highest (> or =35 times per week, 24/102 individuals) compared with the lowest (<10 times per week, 85/190 individuals) category of dairy consumption. Each daily occasion of dairy consumption was associated with a 21% lower odds of IRS (odds ratio, 0.79; 95% confidence interval, 0.70-0.88). These associations were similar for blacks and whites and for men and women. Other dietary factors, including macronutrients and micronutrients, did not explain the association between dairy intake and IRS., Conclusions: Dietary patterns characterized by increased dairy consumption have a strong inverse association with IRS among overweight adults and may reduce risk of type 2 diabetes and cardiovascular disease.

BackgroundHigher levels of intra-abdominal adipose tissue (IAAT) comprising visceral adipose tissue (VAT), intermuscular adipose tissue (IMAT), and liver fat are posited drivers of obesity-related chronic disease risk. Fast food is hypothesized to contribute to IAAT patterns.ObjectivesWe quantified levels of abdominal subcutaneous adipose tissue (SAT), IAAT, and odds of metabolic-associated fatty liver disease (MAFLD) in middle age according to average fast-food intake over the preceding 25 y.MethodsWe analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants underwent 6 clinical exams and measurements over 25 y with computed tomography-measured VAT, SAT, and IMAT (n = 3156), plus MAFLD defined by liver attenuation (≤40 Hounsfield units) and 1 metabolic abnormality at year 25 (2010, n = 3001, n cases = 302). We estimated means of VAT, SAT, IMAT, and liver attenuation at the year 25 exam according to categories of average fast-food intake over the previous 25 y adjusted for sociodemographic and lifestyle factors and logistic regression to estimate the odds ratio of MAFLD at year 25.ResultsWith higher average fast-food intake over 25 y (categorized as follows: never-1×/mo, >1×-3×/mo, 1-

ObjectiveTo examine the associations between change in plant-centered diet quality and type 2 diabetes risk and change in body size.Research design and methodsA prospective study conducted in the U.S. enrolled adults ages 18-30 years in 1985-1986 (examination year [Y0]) and followed them through 2015-2016. We analyzed the associations between change in plant-centered diet quality over 20 years (Y0-Y20) and diabetes (Y20-30; n = 2,534) and change (Y0-Y20 and Y20-30) in BMI, waist circumference (WC), and weight (n > 2,434). Plant-centered diet quality was measured using the A Priori Diet Quality Score (APDQS); a higher score favors nutritionally rich plant foods. Cox regression models were used to assess diabetes risk, and linear regression models were used to examine change in body size.ResultsDuring a mean follow-up of 9.3 (± 1.7) years, 206 case subjects with incident diabetes were observed. In multivariable analysis, participants with the largest increase in APDQS over 20 years had a 48% (95% CI 0.31-0.85; P trend < 0.001) lower risk of diabetes over the subsequent 10 years compared with participants whose score remained stable. Each 1-SD increment in APDQS over 20 years was associated with lower gains in BMI (-0.39 kg/m2; SE 0.14; P = 0.004), WC (-0.90 cm; SE 0.27; P < 0.001) and weight (-1.14 kg; SE 0.33; P < 0.001) during the same period, but not with subsequent changes.ConclusionsYoung adults who increased plant-centered diet quality had a lower diabetes risk and gained less weight by middle adulthood.

BackgroundObese adults who are free from metabolic risk factors may develop risk factors over time. Our objective was to characterize development of obesity and duration of metabolically healthy obese (MHO) over 30 years.MethodsParticipants in CARDIA who developed obesity (BMI ≥ 30 kg/m2) at follow-up exams during years 7, 10, 15, 20, 25, and 30 were analyzed. MHO was defined as obese and having 0 or 1 risk factor: ≥SBP/DBP 130/85 mmHg; fasting glucose ≥100 mg/dL/5.55 mmol/L; fasting triglycerides (≥150 mg/dL/1.69 mmol/L); and HDL-C (men