Metabolically favorable adiposity and bone mineral density: a Mendelian randomization analysis.

OBJECTIVE: This analysis assessed the putative causal association between genetically predicted percent body fat and areal bone mineral density (aBMD) and, more specifically, the association between genetically predicted metabolically "favorable adiposity" (MFA) and aBMD at clinically relevant bone sites. METHODS: Mendelian randomization was used to assess the relationship of MFA and percent body fat with whole-body, lumbar spine, femoral neck, and forearm aBMD. Sex-stratified and age-stratified exploratory analyses were conducted. RESULTS: In all MR analyses, genetically predicted MFA was inversely associated with aBMD for the whole body (ß = -0.053, p = 0.0002), lumbar spine (ß = -0.075; p = 0.0001), femoral neck (ß = -0.045; p = 0.008), and forearm (ß = -0.115; p = 0.001). This negative relationship was strongest in older individuals and did not differ by sex. The relationship between genetically predicted percent body fat and aBMD was nonsignificant across all Mendelian randomization analyses. Several loci that were associated at a genome-wide significance level (p < 5 × 10-8 ) in opposite directions with body fat and aBMD measures were also identified. CONCLUSIONS: This study did not support the hypothesis that MFA protects against low aBMD. Instead, it showed that MFA may result in lower aBMD. Further research is needed to understand how MFA affects aBMD and other components of bone health such as bone turnover, bone architecture, and osteoporotic fractures.

Visceral adipose tissue and cardiometabolic risk factors in young Hispanic and non-Hispanic girls.

Background: Risk factors for cardiometabolic diseases (e.g., type 2 diabetes, cardiovascular disease) can begin developing in childhood. Elevated body mass index (BMI) is associated with greater likelihood of developing such diseases; however, this relationship varies by race and ethnicity. Notably, Hispanics tend to have high rates of obesity and are disproportionately affected by type 2 diabetes. We aimed to determine if visceral adiposes tissue (VAT) is associated with cardiometabolic risk factors (i.e., triglycerides, cholesterol, insulin resistance, C-reactive protein, and blood pressure), independent of BMI percentile, in a sample of primarily Hispanic adolescent girls. Methods and results: A total of 337 girls (73% Hispanic) took part in the cross-sectional study. Hispanic girls generally had greater BMI percentile, VAT, and cardiometabolic risk factors compared to non-Hispanic girls. Multiple linear regression was used to assess the relationships between Dual-energy X-ray Absorptiometry (DXA)-derived VAT and cardiometabolic outcomes, controlling for BMI percentile (<85th percentile or ≥85th percentile), age, ethnicity (Hispanic/non-Hispanic), and Tanner stage. Significant interactions between VAT and BMI percentile were identified for almost all cardiometabolic outcomes. Upon stratification, the association between VAT and cardiometabolic outcomes was strongest in girls ≥85th BMI percentile, as compared to girls <85th percentile. However, VAT was only significantly associated with higher triglycerides (girls ≥85th percentile) and higher insulin resistance (both BMI percentiles) after stratification. Conclusion: VAT was associated with increased triglycerides and insulin resistance in girls with overweight or obesity. These findings warrant further investigation between VAT and cardiometabolic health in Hispanic adolescents who tend to accumulate more adipose tissue during adolescence.

Parent Involvement in Diet or Physical Activity Interventions to Treat or Prevent Childhood Obesity: An Umbrella Review.

Parents substantially influence children's diet and physical activity behaviors, which consequently impact childhood obesity risk. Given this influence of parents, the objective of this umbrella review was to synthesize evidence on effects of parent involvement in diet and physical activity treatment and prevention interventions on obesity risk among children aged 3-12 years old. Ovid/MEDLINE, Elsevier/Embase, Wiley/Cochrane Library, Clarivate/Web of Science, EBSCO/CINAHL, EBSCO/PsycInfo, and Epistemonikos.org were searched from their inception through January 2020. Abstract screening, full-text review, quality assessment, and data extraction were conducted independently by at least two authors. Systematic reviews and meta-analyses of diet and physical activity interventions that described parent involvement, included a comparator/control, and measured child weight/weight status as a primary outcome among children aged 3-12 years old were included. Data were extracted at the level of the systematic review/meta-analysis, and findings were narratively synthesized. Of 4158 references identified, 14 systematic reviews and/or meta-analyses (eight treatment focused and six prevention focused) were included and ranged in quality from very low to very high. Our findings support the inclusion of a parent component in both treatment and prevention interventions to improve child weight/weight status outcomes. Of note, all prevention-focused reviews included a school-based component. Evidence to define optimal parent involvement type and duration and to define the best methods of involving parents across multiple environments (e.g., home, preschool, school) was inadequate and warrants further research. PROSPERO registration: CRD42018095360.

Metabolically Healthy/Unhealthy Overweight/Obesity Associations With Incident Heart Failure in Postmenopausal Women: The Women's Health Initiative.

BACKGROUND: Obesity is associated with an increased risk of heart failure (HF); however, how metabolic weight groups relate to HF risk, especially in postmenopausal women, has not been demonstrated. METHODS: We included 19 412 postmenopausal women ages 50 to 79 without cardiovascular disease from the Women's Health Initiative. Normal weight was defined as a body mass index ≥18.5 and <25 kg/m2 and waist circumference <88 cm and overweight/obesity as a body mass index ≥25 kg/m2 or waist circumference ≥88 cm. Metabolically healthy was based on <2 and unhealthy ≥2 cardiometabolic traits: triglycerides ≥150 mg/dL, systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg or blood pressure medication, fasting glucose ≥100 mg/dL or diabetes medication, and HDL-C (high-density lipoprotein cholesterol) <50 mg/dL. Risk factor-adjusted Cox regression examined the hazard ratios (HRs) for incident hospitalized HF among metabolically healthy normal weight (reference), metabolically unhealthy normal weight, metabolically healthy overweight/obese, and metabolically unhealthy overweight/obese. RESULTS: Among our sample, 455 (2.34%) participants experienced HF hospitalizations over a mean follow-up time of 11.3±1.1 years. Compared with metabolically healthy normal weight individuals, HF risk was greater in metabolically unhealthy normal weight (HR, 1.66 [95% CI, 1.01-2.72], P=0.045) and metabolically unhealthy overweight/obese individuals (HR, 1.95 [95% CI, 1.35-2.80], P=0.0004), but not metabolically healthy overweight/obese individuals (HR, 1.15 [95% CI, 0.78-1.71], P=0.48). Subdividing the overweight/obese into separate groups showed HRs for metabolically unhealthy obese of 2.62 (95% CI, 1.80-3.83; P<0.0001) and metabolically healthy obese of 1.52 (95% CI, 0.98-2.35; P=0.06). CONCLUSIONS: Metabolically unhealthy overweight/obese and metabolically unhealthy normal weight are associated with an increased risk of HF in postmenopausal women.

Influence of Changes in Soft Tissue Composition on Changes in Bone Strength in Peripubertal Girls: The STAR Longitudinal Study.

Obesity and osteoporosis remain two major public health concerns. Soft tissue composition and bone are interrelated; however, it is still not well understood how changes in adiposity during adolescence affect bone development. The aim of this study was to assess how changes in DXA-derived total body lean mass (TBLM) and total body fat mass (TBFM) associate with 2-year changes in bone outcomes at the 20% femur, 66% tibia, 66% radius, and 4% tibia, as measured by pQCT, during the years surrounding the onset of menarche in a cohort of 9- to 12-year-old (baseline) adolescent girls (70% Hispanic). From baseline to 2-year follow-up, girls showed statistically significant increases in all bone outcomes, except radial endosteal circumference. In separate linear regression models, change in TBLM and change in TBFM were both positively associated with 2-year changes in bone outcomes at all measured bone sites, after controlling for relevant covariates. However, when change in TBLM and change in TBFM were included in the same model, change in TBLM was the predominant predictor of bone outcomes, explaining 4% to 14% of the variance in bone strength outcomes. Change in TBFM remained a positive predictor of tibia polar strength strain index (SSIp) (2% variance explained). A significant interaction between change in TBFM and menarcheal status was identified at the radius for SSIp and indicated that greater gains in TBFM were beneficial for SSIp in girls that were premenarcheal at baseline but detrimental for girls who were postmenarcheal at baseline. The overall findings suggest that changes in TBLM during the peripubertal years have a greater influence on bone outcomes than changes in TBFM. While gains in TBFM might benefit the weight bearing 66% tibia, greater gains in TBFM may be detrimental to bone development at the non-weight bearing 66% radius after the onset of menarche. © 2020 American Society for Bone and Mineral Research (ASBMR).

Sociodemographic and metabolic risk characteristics associated with metabolic weight categories in the Women's Health Initiative.

To identify sociodemographic and metabolic correlates of weight categories in postmenopausal women. METHODS: The Women's Health Initiative enrolled 161 808 postmenopausal women ages 50-79. We included those free of cardiovascular disease (CVD) and with CVD risk factors and biomarkers (n = 19 412). Normal weight was defined as a BMI ≥18.5 and <25 kg/m2 and waist circumference <88 cm and overweight/obesity as a BMI ≥25 kg/m2 or waist circumference ≥88 cm. Metabolically healthy was based on <2 and metabolically unhealthy ≥2 traits: triglycerides ≥150 mg/dl, systolic blood pressure (BP) ≥130 mmHg or diastolic BP ≥85 mmHg or antihypertensives or diuretics, fasting glucose ≥100 mg/dl or diabetes medication, and high-density lipoprotein cholesterol <50 mg/dl. Polytomous multinomial logistic regression with generalized link logit function provided the odds of metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO) according to demographic and risk factor measures. RESULTS: Among the 19 412 postmenopausal women, 2369 (12.2%) participants had prevalent diabetes. Advanced age was associated with an increased odds of MUHNW as compared with the MHNW after adjusting for covariates [odds ratio (OR) 1.04, P < 0.0001]. Black/African American ethnicity was associated with a decreased odds of MUHNW (OR 0.64, P < 0.0001) and MUHO (OR 0.77, P = 0.0004), while an increased odds for MHO (OR 1.50, P < 0.0001) as compared with White MHNW. CONCLUSIONS: Advanced age and ethnicity are important indicators of metabolic weight categories among postmenopausal women.

Incidence of diabetes according to metabolically healthy or unhealthy normal weight or overweight/obesity in postmenopausal women: the Women's Health Initiative.

OBJECTIVE: To determine the relationship of metabolic weight categories with incident diabetes mellitus (DM) in postmenopausal women. METHODS: The Women's Health Initiative (WHI) enrolled 161,808 postmenopausal women aged 50 to 79 years. We included those with cardiovascular disease (CVD) biomarkers and free of CVD and prevalent DM (n = 17,043) at baseline. Normal weight was defined as a body mass index (BMI) ≥18.5 and <25 kg/m, and waist circumference (WC) <88 cm and overweight/obesity as a BMI ≥25 kg/m or WC ≥88 cm. Metabolically healthy was based on <2 and metabolically unhealthy ≥2 traits of the following: triglycerides ≥150 mg/dL, systolic blood pressure (BP) ≥130 mm Hg or diastolic BP ≥85 mm Hg, or antihypertensives or diuretics, fasting glucose ≥100 mg/dL or DM medication, and high-density lipoprotein cholesterol <50 mg/dL. Cox regression was performed to determine the risk of incident DM among metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO). RESULTS: Among our sample, 2,253 (13.3%) participants developed DM over a mean ± standard deviation follow-up time of 15.6 ±â€Š3.4 years. Compared with MHNW (n = 162 incident DM cases), an increased risk of incident DM was observed in MUHNW (n = 102 cases) (hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.74-2.88, P < 0.0001), MHO (n = 624 cases) (HR 1.68, 95% CI 1.40-2.00, P < 0.0001), and MUHO (n = 1,365 cases) (HR 4.51, 95% CI 3.82-5.35, P < 0.0001). CONCLUSIONS: Among postmenopausal women, MUHNW and MHO confer an approximate doubling in the risk and MUHO more than a four-fold increased risk for developing DM.

Feasibility of a family-focused YMCA-based diabetes prevention program in youth: The E.P.I.C. Kids (Encourage, Practice, and Inspire Change) Study.

Efficacious lifestyle modification programs for children at risk of type 2 diabetes (T2D) have not been well established outside of clinical settings. In this study, the feasibility of a family-focused, YMCA-based prevention program for children at risk of T2D was evaluated between September 2015 and July 2016 in Tucson, Arizona. A 12-week YMCA-led lifestyle intervention was adapted for 9-12-year-old children and their families to encourage healthy eating, physical activity, and supportive home environments. Two YMCA locations were randomized to offer either a face-to-face lifestyle coach-led intervention or an alternating face-to-face and digitally-delivered intervention. Program feasibility and preliminary effects on child anthropometric and behavioral outcomes were assessed at baseline and post-intervention. Changes were assessed using linear regression combining delivery formats, with adjustment for clustering of participants within site/format. Forty-eight children (10.9 ±â€¯1.2 years old; 45% female; 40% Hispanic; 43% White; 87% obese) and their parents enrolled, and 36 (75%) completed 12-week measures. Weekly program attendance averaged 61%. Participants and coaches highly rated program content and engagement strategies. Statistically significant changes in child BMI-z score (-0.05, p = 0.03) and family food and physical activity environment (+5.5% family nutrition and physical activity score, p = 0.01) were observed. A YMCA-led family-focused T2D intervention was feasible for the YMCA and participants and effects on child weight, behavior, and the home environment warranted further investigation.

Physical activity and weight gain after smoking cessation in postmenopausal women.

OBJECTIVE: Weight gain frequently occurs after smoking cessation. The objective of this study was to examine whether weight gain after smoking cessation was attenuated by physical activity (PA) in postmenopausal women. METHODS: A total of 4,717 baseline smokers from the Women's Health Initiative were followed for 3 years. One thousand two hundred eighty-two women quit smoking, and 3,435 continued smoking. Weight was measured at baseline and at the year 3 visit. PA was assessed at both times by self-report, summarized as metabolic equivalent task-hours per week. Multiple linear regression models were used to assess the association between PA and postcessation weight gain, adjusting for potential confounding factors. RESULTS: Compared with continuing smokers, quitters gained an average of 3.5 kg (SD = 5.6) between the baseline and year 3 visit. Quitters with decreased PA had the highest amount of weight gain (3.88 kg, 95% CI: 3.22-4.54); quitters with increased PA (≥15 metabolic equivalent task-hours /week) had the lowest weight gain (2.55 kg, 95% CI: 1.59-3.52). Increased PA had a stronger beneficial association for postcessation weight gain for women with obesity compared to normal weight women. Quitters who had low PA at baseline and high PA at year 3 and were also enrolled in a dietary modification intervention had nonsignificant weight gain (1.88 kg, 95% CI: -0.21-3.96) compared with continuing smokers. CONCLUSIONS: Our data demonstrate that even a modest increase in PA (equivalent to current recommendations) can attenuate weight gain after quitting smoking among postmenopausal women, especially in combination with improved diet.

Relationship of cardiometabolic risk biomarkers with DXA and pQCT bone health outcomes in young girls.

BACKGROUND: Excess weight exerts the positive effect of mechanical loading on bone during development whereas obesity-related metabolic dysfunction may have a detrimental impact. In adults, the presence of metabolic syndrome and type 2 diabetes has been associated with compromised bone density, quality, and strength, and an increased incidence of fractures. The few studies that have investigated the role of cardio-metabolic disease risk biomarkers (CMR) on bone strength in children have given conflicting results. The aim of this study was to assess the combined and independent relationships of cardio-metabolic biomarkers with total body and regional bone parameters in young girls. METHODS: In 306, 9-12 year old girls, measures of whole body fat and lean mass, areal bone mineral density (aBMD), bone mineral content (BMC), and bone area (BA) were obtained by dual-energy x-ray absorptiometry (DXA). Bone mineral density (vBMD), geometry, and strength of metaphyseal and diaphyseal regions of the femur and tibia and a diaphyseal region of the radius were measured using peripheral quantitative computed tomography (pQCT). Fasting serum measures of CMRs included, fasting glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), systolic and diastolic blood pressure (SBP and DBP), and C-reactive protein (CRP). Multiple linear regression was used to assess the independent associations of a single CMR with total body and peripheral measures of bone strength after controlling for the other CMRs, plus total body soft tissue, and other relevant covariates. Also, a standardized total CMR composite score, calculated by standardizing to z-scores and then summing z-scores of each CMR biomarker, was regressed with total body and regional bone measures to assess the relationship of a cluster of risk factors with bone health. RESULTS: Total CMR composite score had inverse associations (p < 0.001) with DXA total BMC and BA. Inverse associations (p < 0.05) of CMR risk score with pQCT regional bone measures occurred with total and trabecular BA at the 4% tibia. Of the individual CMRs, HOMA-IR and CRP were significant predictors of total body bone measures by DXA accounting for ~1-5% of the variance in BMC, BA, and/or aBMD. HOMA-IR was the main predictor of regional pQCT bone outcomes, accounting for the most variance in trabecular vBMD (2.6%) and BSI (3.8%) at the 4% tibia. Most markers of dyslipidemia (TG, HDL-C, LDL-C) and hypertension (SBP, DBP) were not associated (p > 0.05) with any total body or regional bone outcomes with the exception of the inverse relationship of LDL-C with total and trabecular BA and the positive relationship of DBP with cortical vBMD at the radius. CONCLUSION: Of the obesity-related metabolic impairments, insulin resistance and chronic inflammation may compromise whole body bone development in young girls. In particular, trabecular bone, such as that found at the metaphysis of long bones, may be more susceptible to the detrimental effects associated with obesity-related metabolic dysfunction.

Interaction of body mass index or waist-to-hip ratio and sun exposure associated with nonmelanoma skin cancer: A prospective study from the Women's Health Initiative.

BACKGROUND: The incidence of nonmelanoma skin cancer (NMSC) exceeds the incidence of all other types of cancers combined. Cumulative sun exposure and intermittent sun exposure are known risk factors for the development of NMSC. Because obesity has been shown to decrease the risk of NMSC incidence, this study investigated whether the risk of NMSC with sun exposure was consistent across different levels of body size. METHODS: Body size was assessed with the body mass index (BMI) and the waist-to-hip ratio (WHR). Sun exposure was assessed in watts and langleys and by the amount of time spent outdoors per day in the summer during a person's 30s. RESULTS: Among 71,645 postmenopausal women eligible for inclusion in this study, 13,351 participants (18.6%) developed NMSC. A BMI ≥ 25 kg/m2 or a WHR ≥ 0.80 was associated with lower NMSC hazard rates (hazard ratio for BMI, 0.78; hazard ratio for WHR, 0.89); however, the association between higher levels of sun exposure and a higher risk of NMSC was more apparent among women with a BMI ≥ 25 kg/m2 or a WHR ≥ 0.80 in comparison with those of a normal weight (P for interaction for BMI < .001; P for interaction for WHR = .022). CONCLUSIONS: Although most studies have considered sun exposure as a covariate, none have addressed the potential interaction of body size with sun exposure; therefore, the effect size of being overweight or obese may have been overestimated. In comparison to the normal-weight group, those in the overweight group had increasingly higher hazard rates with increasing sun exposure. Further studies are warranted to investigate how increased weight interacts with sun exposure to influence skin cancer pathogenesis.

Association Between Sarcopenic Obesity and Falls in a Multiethnic Cohort of Postmenopausal Women.

OBJECTIVES: To investigate associations between sarcopenia, obesity, and sarcopenic obesity and incidence of falls in a racially and ethnically diverse cohort of healthy postmenopausal women. DESIGN: Prospective cohort study. SETTING: Three Women's Health Initiative (WHI) clinical centers (Tucson-Phoenix, AZ; Pittsburgh, PA; Birmingham, AL). PARTICIPANTS: Postmenopausal women aged 50 to 79 enrolled in the WHI who underwent bone and body composition scans using dual-energy x-ray absorptiometry at baseline (N = 11,020). MEASUREMENTS: Sarcopenia was defined as the lowest 20th percentile of appendicular lean mass, correcting for height and body fat. Obesity was defined as a body fat percentage greater than 42%. Sarcopenic obesity was defined as co-occurrence of sarcopenia and obesity. The fall outcome was defined as falling 2 or more times in any year during 7 years of follow-up. The risk of falls associated with sarcopenic obesity were analyzed using log binomial regression models stratified according to age and race/ethnicity. RESULTS: Sarcopenic obesity was associated with greater risk of falls in women aged 50 to 64 (relative risk (RR) = 1.35, 95% confidence interval (CI)=1.17-1.56) and 65 to 79 (RR = 1.21, 95% CI=1.05-1.39). Sarcopenic obesity related fall risk was higher in Hispanic women (RR = 2.40, 95% CI=1.56-3.67) than non-Hispanic white women (RR = 1.24, 95% CI=1.11-1.39). CONCLUSION: In a multiethnic cohort of postmenopausal women, sarcopenic obesity-related fall risk was high in women younger than 65 and those age 65 and older. Sarcopenic obesity posed the highest risk for falls in Hispanic women. The findings support identification of causal factors and health disparities in sarcopenic obesity to customize fall prevention strategies and ameliorate this significant public health burden. J Am Geriatr Soc 66:2314-2320, 2018.

Anthropometry Versus Imaging for Prediction of Inflammation Among Hispanic Girls.

OBJECTIVE: This study aimed to compare total and regional estimates of body composition, by direct and indirect techniques, for the optimal prediction of C-reactive protein (CRP) among young (aged 9-12 years) Hispanic girls (N = 232). METHODS: Standard anthropometric techniques were used to measure height, weight, and waist circumference. Dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) assessed body composition. Fasting serum CRP was measured by the AU5812 Clinical Chemistry Analyzer (Beckman Coulter, Brea, California). Associations between each total and regional body composition parameter and CRP were tested using linear regression (log-transformed, continuous CRP) and ordinal logistic regression (CRP < 1.0, ≥ 1.0-2.9, and ≥ 3.0 mg/L), controlling for maturation, dietary energy, physical activity, and medications. RESULTS: All measures of total and regional body fat were positively associated with CRP (P < 0.0001) except for intermuscular fat by pQCT. There were no clinically relevant differences in their association with CRP between anthropometric (BMI; waist circumference) and DXA-derived (total fat and regional fat: trunk, gynoid, android fat, leg) measures of fat. CONCLUSIONS: Measurement of body habitus in Hispanic girls, by multiple commonly available means, predicts CRP equally well.

Relationship between fat distribution and cardiometabolic risk in Hispanic girls.

OBJECTIVE: In adults, certain body fat depots have greater impact on cardiometabolic risk than total adiposity. Whether similar relationships exist in children is uncertain. The aim of this study was to examine the relationships among dual x-ray absorptiometry (DXA) measures of body fat distribution and total body adiposity with cardiometabolic risk factors in Hispanic girls. METHODS: Measures of total percent body fat, percent of total fat within the android, gynoid, leg, and trunk regions, and cardiometabolic biomarkers (insulin, glucose, homeostatic model assessment of insulin resistance (HOMA-IR), triglycerides (TG), low and high lipoprotein cholesterol (LDL-C, HDL-C)) were obtained from 232 Hispanic girls (age 10.7 ±1.1 years). Regression models for each metabolic parameter were run against adiposity measures. Partial correlations of the adiposity measures were used to compare associations between adiposity measures and the cardiometabolic risk factors, controlling for somatic maturation. RESULTS: Total and regional adiposity were significantly related with cardiometabolic risk factors (P < 0.05) except fasting glucose. The partial correlations of total and regional adiposity measures with each cardiometabolic biomarker were similar. More variance was explained for insulin and the HOMA-IR (33%-43%) than other risk factors. Partial correlations for the percentage of total fat in the gynoid and leg regions with insulin, HOMA-IR, TG, and LDL-C were negative, and positive with HDL-C. CONCLUSION: Measures of total and regional fat perform similarly in predicting cardiometabolic risk in Hispanic girls. A higher proportion of fat distributed in the gynoid or leg region is associated with lower cardiometabolic risk.

Body composition and physical function in the Women's Health Initiative Observational Study.

Physical function is critical for mobility and quality of life. We hypothesized that higher total lean mass is associated with higher physical function, and body fat inversely associated, among postmenopausal women. Women's Health Initiative Observational Study participants at Pittsburgh, PA; Birmingham, AL; and Tucson-Phoenix, AZ (1993-1998) completed dual-energy X-ray absorptiometry scans and the Rand SF-36 questionnaire at baseline and 3 y (N = 4526). Associations between quartiles (Q1-4) of lean or fat mass and physical function were tested using linear regression, adjusted for demographics, lifestyle factors, medical history, and scanner serial number. At baseline, participants had a mean ±â€¯SD age of 63.4 ±â€¯7.4 y and BMI of 27.4 ±â€¯5.8 kg/m2. Higher percent lean mass was positively associated with physical function at baseline (Q4, 83.6 ±â€¯0.6 versus Q1, 74.6 ±â€¯0.7; p < 0.001), while fat mass (kg and %) was inversely associated (e.g., Q4, 73.7 ±â€¯0.7 versus Q1, 84.2 ±â€¯0.7 kg; ptrend < 0.001). Physical function had declined across the cohort at 3 y; the highest relative lean mass quartile at baseline conferred a lesser decline in physical function than the lowest (Q4, -3.3 ±â€¯0.6 versus Q1-7.0 ±â€¯0.6; ptrend < 0.001), while the highest fat mass quartile (% and kg) conferred greater decline (ex. Kg Q4, -6.7 ±â€¯0.7 versus Q1-2.8 ±â€¯0.6; ptrend < 0.001). Increased fat mass (≥5%), but not lean mass, was associated with lower physical function at 3 y (p < 0.001). Adiposity, as well as lean mass, requires consideration in the prediction of physical function among postmenopausal women over time.

Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE.

BACKGROUND/OBJECTIVES: Physical activity (PA) protects against a wide range of diseases. Habitual PA appears to be heritable, motivating the search for specific genetic variants that may inform efforts to promote PA and target the best type of PA for each individual. SUBJECTS/METHODS: We used data from the UK Biobank to perform the largest genome-wide association study of PA to date, using three measures based on self-report (nmax = 377,234) and two measures based on wrist-worn accelerometry data (nmax = 91,084). We examined genetic correlations of PA with other traits and diseases, as well as tissue-specific gene expression patterns. With data from the Atherosclerosis Risk in Communities (ARIC; n = 8,556) study, we performed a meta-analysis of our top hits for moderate-to-vigorous PA (MVPA). RESULTS: We identified ten loci across all PA measures that were significant in both a basic and a fully adjusted model (p < 5 × 10-9). Upon meta-analysis of the nine top hits for MVPA with results from ARIC, eight were genome-wide significant. Interestingly, among these, the rs429358 variant in the APOE gene was the most strongly associated with MVPA, whereby the allele associated with higher Alzheimer's risk was associated with greater MVPA. However, we were not able to rule out possible selection bias underlying this result. Variants in CADM2, a gene previously implicated in obesity, risk-taking behavior and other traits, were found to be associated with habitual PA. We also identified three loci consistently associated (p < 5 × 10-5) with PA across both self-report and accelerometry, including CADM2. We found genetic correlations of PA with educational attainment, chronotype, psychiatric traits, and obesity-related traits. Tissue enrichment analyses implicate the brain and pituitary gland as locations where PA-associated loci may exert their actions. CONCLUSIONS: These results provide new insight into the genetic basis of habitual PA, and the genetic links connecting PA with other traits and diseases.

Effect of cardiometabolic risk factors on the relationship between adiposity and bone mass in girls.

BACKGROUND/OBJECTIVE: Childhood obesity has been separately associated with cardiometabolic risk factors (CMRs) and increased risk of fracture. However, both augmented and compromised bone mass have been reported among overweight/obese children. Metabolic dysfunction, often co-existing with obesity, may explain the discrepancy in previous studies. The aim of this study was to examine whether the relationship between adiposity and dual-energy X-ray absorptiometry (DXA) derived bone mass differed in young girls with and without CMR(s). SUBJECTS/METHODS: Whole-body bone and body composition measures by DXA and measures of CMR (fasting glucose, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic and diastolic blood pressure, waist circumference (WC)) were obtained from 307, 9- to 12-year-old girls. Girls with 1 or ≥ 2 CMR(s) were considered to be at risk (vs. no CMR). Multiple linear regression was used to test the relationship of total fat mass with total body bone mineral content (BMC) after controlling for height, lean mass, CMR risk, and other potential confounders. RESULTS: There was a significant interaction between CMR risk and total body fat mass. When girls were stratified by CMR group, all groups had a significant positive relationship between fat mass and BMC (p < 0.05), however, girls with ≥ 2 CMRs had a lower BMC for a given level of body fat. Total body fat was not significantly related to bone mineral density (p > 0.05). CONCLUSION: Fat mass has a positive relationship with BMC even after controlling for lean mass. However, the positive relationship of fat mass with BMC may be attenuated if multiple CMRs are present.

Stratified Probabilistic Bias Analysis for Body Mass Index-related Exposure Misclassification in Postmenopausal Women.

BACKGROUND: There is widespread concern about the use of body mass index (BMI) to define obesity status in postmenopausal women because it may not accurately represent an individual's true obesity status. The objective of the present study is to examine and adjust for exposure misclassification bias from using an indirect measure of obesity (BMI) compared with a direct measure of obesity (percent body fat). METHODS: We used data from postmenopausal non-Hispanic black and non-Hispanic white women in the Women's Health Initiative (n=126,459). Within the Women's Health Initiative, a sample of 11,018 women were invited to participate in a sub-study involving dual-energy x-ray absorptiometry scans. We examined indices of validity comparing BMI-defined obesity (≥30 kg/m), with obesity defined by percent body fat. We then used probabilistic bias analysis models stratified by age and race to explore the effect of exposure misclassification on the obesity-mortality relationship. RESULTS: Validation analyses highlight that using a BMI cutpoint of 30 kg/m to define obesity in postmenopausal women is associated with poor validity. There were notable differences in sensitivity by age and race. Results from the stratified bias analysis demonstrated that failing to adjust for exposure misclassification bias results in attenuated estimates of the obesity-mortality relationship. For example, in non-Hispanic white women 50-59 years of age, the conventional risk difference was 0.017 (95% confidence interval = 0.01, 0.023) and the bias-adjusted risk difference was 0.035 (95% simulation interval = 0.028, 0.043). CONCLUSIONS: These results demonstrate the importance of using quantitative bias analysis techniques to account for nondifferential exposure misclassification of BMI-defined obesity. See video abstract at, http://links.lww.com/EDE/B385.

Relative contributions of lean and fat mass to bone strength in young Hispanic and non-Hispanic girls.

BACKGROUND: With the high prevalence of childhood obesity, especially among Hispanic children, understanding how body weight and its components of lean and fat mass affect bone development is important, given that the amount of bone mineral accrued during childhood can determine osteoporosis risk later in life. The aim of this study was to assess the independent contributions of lean and fat mass on volumetric bone mineral density (vBMD), geometry, and strength in both weight-bearing and non-weight-bearing bones of Hispanic and non-Hispanic girls. METHODS: Bone vBMD, geometry, and strength were assessed at the 20% distal femur, the 4% and 66% distal tibia, and the 66% distal radius of the non-dominant limb of 326, 9- to 12-year-old girls using peripheral quantitative computed tomography (pQCT). Total body lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). Multiple linear regression was used to assess the independent relationships of fat and lean mass with pQCT bone measures while adjusting for relevant confounders. Potential interactions between ethnicity and both fat and lean mass were also tested. RESULTS: Lean mass was a significant positive contributor to all bone outcomes (p < 0.05) with the exception of vBMD at diaphyseal sites. Fat mass was a significant contributor to bone strength at weight bearing sites, but did not significantly contribute to bone strength at the non-weight bearing radius and was negatively associated with radius cortical content and thickness. Bone measures did not significantly differ between Hispanic and non-Hispanic girls, although there was a significant interaction between ethnicity and fat mass with total bone area at the femur (p = 0.02) and 66% tibia (p = 0.005) as well as bone strength at the femur (p = 0.03). CONCLUSION: Lean mass is the main determinant of bone strength for appendicular skeletal sites. Fat mass contributes to bone strength in the weight-bearing skeleton but does not add to bone strength in non-weight-bearing locations and may potentially be detrimental. Bone vBMD, geometry, and strength did not differ between Hispanic and non-Hispanic girls; fat mass may be a stronger contributor to bone strength in weight-bearing bones of Hispanic girls compared to non-Hispanic.