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Context: Pediatric studies have shown that aerobic exercise reduces metabolic risk, but dose-response information is not available.Objectives: To test the effect of different doses of aerobic training on insulin resistance, fatness, visceral fat, and fitness in overweight, sedentary children and to test moderation by sex and race.Design, Setting, and Participants: Randomized controlled efficacy trial conducted from 2003 through 2007 in which 222 overweight or obese sedentary children (mean age, 9.4 years; 42% male; 58% black) were recruited from 15 public schools in the Augusta, Georgia, area.Intervention: Children were randomly assigned to low-dose (20 min/d; n = 71) or high-dose (40 min/d; n = 73) aerobic training (5 d/wk; mean duration, 13 [SD, 1.6] weeks) or a control condition (usual physical activity; n = 78).Main Outcome Measures: The prespecified primary outcomes were postintervention type 2 diabetes risk assessed by insulin area under the curve (AUC) from an oral glucose tolerance test, aerobic fitness (peak oxygen consumption [VO2]), percent body fat via dual-energy x-ray absorptiometry, and visceral fat via magnetic resonance, analyzed by intention to treat.Results: The study had 94% retention (n = 209). Most children (85%) were obese. At baseline, mean body mass index was 26 (SD, 4.4). Reductions in insulin AUC were larger in the high-dose group (adjusted mean difference, -3.56 [95% CI, -6.26 to -0.85] × 10(3) μU/mL; P = .01) and the low-dose group (adjusted mean difference, -2.96 [95% CI, -5.69 to -0.22] × 10(3) μU/mL; P = .03) than the control group. Dose-response trends were also observed for body fat (adjusted mean difference, -1.4% [95% CI, -2.2% to -0.7%]; P < .001 and -0.8% [95% CI, -1.6% to -0.07%]; P = .03) and visceral fat (adjusted mean difference, -3.9 cm3 [95% CI, -6.0 to -1.7 cm3]; P < .001 and -2.8 cm3 [95% CI, -4.9 to -0.6 cm3]; P = .01) in the high- and low-dose vs control groups, respectively. Effects in the high- and low-dose groups vs control were similar for fitness (adjusted mean difference in peak VO2, 2.4 [95% CI, 0.4-4.5] mL/kg/min; P = .02 and 2.4 [95% CI, 0.3-4.5] mL/kg/min; P = .03, respectively). High- vs low-dose group effects were similar for these outcomes. There was no moderation by sex or race.Conclusion: In this trial, after 13 weeks, 20 or 40 min/d of aerobic training improved fitness and demonstrated dose-response benefits for insulin resistance and general and visceral adiposity in sedentary overweight or obese children, regardless of sex or race.Trial Registration: clinicaltrials.gov Identifier: NCT00108901. [ABSTRACT FROM AUTHOR]

PURPOSE: To determine the relationship between alcohol use disorders (AUDs) and herpes simplex virus type 2 (HSV-2), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) infections among a sample of sexually active adolescents. METHODS: Subjects were 240 sexually active male and female adolescents aged 14 to 21 years (mean 17.5 years) recruited from clinical and community settings in western Pennsylvania between 1991 and 1995; 55% had a lifetime history of AUDs (63 females, 69 males) and 45% did not have a lifetime history of AUDs (57 females, 51 males). Participants provided information about demographic factors and sexual behaviors as well as a serum sample that was assayed for antibodies to HSV-2, HBV, and HIV infections. Multivariate logistic regression was used to determine the independent relationship of AUDs to HSV-2 infections among females. RESULTS: The seroprevalence of HSV-2 infections was 15% among females and 0% among males; the overall prevalence of HBV (1.2%) and HIV (0.4%) infections was very low. Among adolescent females, the seroprevalence of HSV-2 infections was significantly higher among those with an AUD (19%), compared with those without an AUD (10.5%) (adjusted odds ratio 8.1, 95% confidence interval 1.5-44.8, p =.017). CONCLUSIONS: Adolescent women with an AUD appear to be at substantially increased risk of HSV-2 infection. These results highlight the need to address sexually transmitted diseases among adolescents with alcohol problems. [ABSTRACT FROM AUTHOR]

Context: Adults with cerebral palsy (CP) display a higher prevalence of cardiometabolic disease compared with the general population. Studies examining cardiometabolic disease risk in children with CP are limited., Objective: The purpose of this study was to determine if children with CP exhibit higher cardiometabolic risk than typically developing children, and to examine its relationship with visceral adiposity and physical activity., Methods: Thirty ambulatory children with CP and 30 age-, sex-, and race-matched typically developing control children were tested for blood lipids, glucose, and the homeostatic model assessment of insulin resistance (HOMA-IR). Visceral fat was assessed using dual-energy x-ray absorptiometry. Physical activity was assessed using accelerometer-based monitors., Results: Children with CP had higher total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (non-HDL-C), glucose, prevalence of dyslipidemia, prevalence of prediabetes, and visceral fat mass index (VFMI) and lower physical activity than controls (all P < .05). In the groups combined, non-HDL-C and glucose were positively related to VFMI ( r = 0.337 and 0.313, respectively, P < .05), and non-HDL-C and HOMA-IR were negatively related to physical activity ( r = -0.411 and -0.368, respectively, P < .05). HOMA-IR was positively related to VFMI in children with CP ( r = 0.698, P < .05), but not in controls. Glucose was not related to physical activity in children with CP, but it was negatively related in controls ( r = -0.454, P < .05)., Conclusion: Children with CP demonstrate early signs of cardiometabolic disease, which are more closely related to increased visceral adiposity than decreased physical activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: Childhood obesity and inactivity are associated with cardiovascular risk. Evidence is limited for exercise effects on arterial health in children., Methods: One hundred and seventy-five inactive children with overweight or obesity (8-11 years, ≥85th percentile BMI, 61% female, 87% Black, 73% with obesity) were randomized to an 8-month daily after-school aerobic exercise program (40 min/day, n = 90) or a sedentary control condition (n = 85). Carotid-femoral pulse wave velocity (PWV, primary outcome, arterial stiffness), fitness, adiposity, blood pressure (BP), glucose, insulin resistance, lipids, and C-reactive protein were measured at baseline and posttest (8 months). Adiposity, fitness, and BP were measured again at follow-up, 8-12 months later. Intent-to-treat analyses were conducted using mixed models., Results: The study had 89% retention, with attendance of 59% in exercise and 64% in the control condition, and vigorous exercise participation (average heart rate 161 ± 7 beats/min). Compared with controls, the exercise group had twice the improvement in fitness (VȮ 2 peak, 2.7 (95% CI 1.8, 3.6) vs. 1.3 (0.4, 2.3) mL/kg/min) and adiposity (-1.8 (-2.4, -1.1) vs. -0.8 (-1.5, -0.1)%), each p = 0.04, and a large improvement in HDL-cholesterol (0.13 (0.075, 0.186) vs. -0.028 (-0.083, 0.023) mmol/L, p < 0.0001). There was no group × time effect on other outcomes at 8 months, or on any outcomes at follow-up. The change in PWV at 8 months correlated with changes in insulin and insulin resistance (both r = 0.32), diastolic BP (r = 0.24), BMI (r = 0.22), and adiposity (r = 0.18)., Conclusions: Eight months of aerobic exercise training improved fitness, adiposity, and HDL-cholesterol levels, but did not reduce arterial stiffness in children with excess weight. PWV improved as a function of insulin resistance, BP, BMI, and adiposity. Weight loss may be required to improve arterial stiffness. Exercise benefits waned after discontinuing the program.

Background: It is unknown to what extent higher maternal blood pressure (BP) in early postpartum impacts the relationship between higher maternal weight status and greater infant weight gain in early postpartum., Objective: To evaluate the mediating role of higher maternal BP at 1 month postpartum on the association between higher maternal weight status at 1 month postpartum and greater infant weight gain over 6 months postpartum., Methods: Participants were 169 Hispanic mother-infant pairs. Maternal body mass index (BMI) and BP were assessed at 1 month postpartum. Infant weight was measured at 1 and 6 months postpartum to calculate weight-for-age z scores (WAZ). Multiple linear regression models were used for prediction, and Sobel test was used to determine mediation., Results: Controlling for maternal pre-pregnancy BMI, age, delivery mode, infant sex, and infant birth weight revealed that both maternal BMI (β = .29) and BP (β = .32) predicted infant WAZ gain (both P ≤ .03). However, the relationship between infant WAZ gain and maternal BMI was no longer significant after further adjustment for maternal BP, which remained significant (P < .05). Maternal BP explained 23.6% (Sobel T = 2.01) of the association between maternal BMI at 1 month and infant WAZ gain over 6 months., Conclusion: Our data suggest that higher maternal weight status at 1 month postpartum is related to greater infant weight gain over 6 months postpartum, and this relationship is mediated by higher maternal BP at 1 month postpartum., (© 2019 World Obesity Federation.)

Background: Perinatal growth has important implications for cardiac development. Low birth weight is associated with cardiovascular (CV) events and mortality, and animal studies have shown that fetal growth restriction is associated with cardiac remodeling in the perinatal period leading to a permanent loss of cardiomyocyte endowment and compensatory hypertrophy., Aims: To determine associations of birthweight (BW) and multiple proportionality indexes (body mass index (BMI); weight/length 2 and Ponderal index (PI); weight/length 3 ) at birth on one hand, with left ventricular (LV) structure and function during adolescence., Subjects: 379 healthy adolescents aged 14-18 years in Augusta, Georgia., Outcome Measures: LV structure and function parameters, including intraventricular septal thickness in diastole (IVSd), LV internal dimension in diastole (LVIDd), LV internal diameter in systole (LVIDs), LV posterior wall thickness in diastole (LVPWd), relative wall thickness (RWT), midwall fractional shortening (MFS), and ejection fraction, were assessed by echocardiography., Results: When associations of birthweight, birth BMI, and birth PI with LV structure and function parameters were separately evaluated with linear regression adjusting for age, sex, race, Tanner stage, socioeconomic status, and physical activity, significant positive associations of BW with LVIDd (P = 0.004), birth BMI with LV mass index (P = 0.01), and birth PI with IVSd (P = 0.02), LVPWd (P = 0.03), and LV mass index (P = 0.002) were identified. When LV structure and function parameters were compared across PI tertiles, a significant U-shaped trend for LV mass index (P quadratic  = 0.04) was identified., Conclusions: Our adolescent data suggest that proportionality at birth may identify associations between perinatal growth and cardiac remodeling independent of birthweight alone., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Objectives: Investigations in older individuals suggest that adequate nutrition and physical activity are particularly important to skeletal muscle health; however, data in adolescents are scant and equivocal. The objective was to determine the associations among diet, physical activity and skeletal muscle mass in adolescents., Methods: We assessed diet with four to seven 24-h recalls and physical activity by accelerometry in 640 adolescents. Using total body measures of fat-free soft tissue mass and fat mass assessed by dual-energy X-ray absorptiometry, the skeletal muscle mass index (SMMI) was derived by adjusting fat-free soft tissue mass for fat mass in addition to height., Results: Skeletal muscle mass index (SMMI) was negatively associated with consumption of sugar-sweetened beverages (standardized beta coefficient [β] = -0.10, P = 0.001) and saturated fats (β = -0.28, P < 0.001). SMMI was positively associated with physical activity (moderate + vigorous) (β = 0.20, P < 0.001). In further analysis, we observed a significant interaction between physical activity and sugar-sweetened beverage intake on SMMI (P = 0.002)., Conclusion: Our study in adolescence suggests that physical activity and consumption of both sugar-sweetened beverages and saturated fats are associated with skeletal muscle mass. More importantly, our findings suggest that sugar-sweetened beverage intake may attenuate the beneficial effects of physical activity on skeletal muscle mass., (© 2018 World Obesity Federation.)

Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D 3 supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D 3 dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH) 2 D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH) 2 D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

Background: Matrix Gla protein (MGP) is a vascular calcification inhibitor dependent upon vitamin K for activation. Evidence suggests that elevated plasma inactive MGP levels (desphospho-uncarboxylated MGP, dp-ucMGP; indicating poorer vascular vitamin K status) are associated with greater cardiovascular disease (CVD) risk. Despite African Americans experiencing highest rates of kidney failure and CVD events, relationships between dp-ucMGP and CVD risk markers have not been examined in this population. We investigated vascular vitamin K status (via plasma dp-ucMGP) between African American hemodialysis (HD) patients and healthy controls, and the associations of dp-ucMGP with arterial stiffness and endothelial function in HD patients only., Methods: In 37 African American HD patients and 37 age- and race-matched controls, plasma dp-ucMGP was measured by enzyme immunoassay as a marker of vascular vitamin K status. Carotid-femoral pulse wave velocity (PWV; arterial stiffness measurement) and brachial artery flow-mediated dilation (FMD; endothelial function measurement) were assessed by applanation tonometry and ultrasound, respectively, in HD patients only., Results: Mean dp-ucMGP levels were 5.6 times higher in HD patients vs. controls (2,139 ± 1,102 vs. 382 ± 181 pmol/l, P < 0.01). Multiple linear regression, adjusting for age, sex, dialysis vintage, diabetes mellitus, CVD history, body mass index, and blood pressure, revealed that dp-ucMGP was independently related to PWV (standardized β = 0.49) and FMD (standardized β = -0.53) (both P < 0.01)., Conclusions: Our data suggest that the higher plasma dp-ucMGP concentrations found in African American HD patients may be associated with greater arterial stiffness and endothelial dysfunction.

Background: Clinical trials are scant and equivocal on whether vitamin D can ameliorate arterial stiffness, particularly in populations at high risk for vitamin D deficiency and cardiovascular disease (CVD). This study determined the dose-response effects of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency., Methods: Seventy overweight African Americans (aged 13-45 years) with serum 25-hydroxyvitamin D [25(OH)D] levels ≤ 20 ng/mL were randomized to monthly oral supplementation of 18,000 IU (~600 IU/day, n = 17), 60,000 IU (~2000 IU/day, n = 18), or 120,000 IU (~4000 IU/day, n = 18) of vitamin D3 or placebo (n = 17) for 16-weeks. The arterial stiffness measurements, carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV, were assessed by applanation tonometry at baseline and 16 weeks., Results: Vitamin D3 supplementation demonstrated a dose-response increase in serum 25(OH)D concentrations between groups (P<0.01). A significant downward linear trend was observed for carotid-femoral PWV (P<0.01), as the mean changes in carotid-femoral PWV across the four treatment groups were 0.13 m/s (95% CI: -0.24, 0.51 m/s) for placebo, 0.02 m/s (95% CI: -0.34, 0.38 m/s) for 600 IU/day group, -0.11 m/s (95% CI: -0.50, 0.27 m/s) for the 2,000 IU/day group, and -0.70 m/s (95% CI: -1.07, -0.32 m/s) for the 4,000 IU/day group. Findings were similar for carotid-radial PWV (P = 0.03), as the mean changes in carotid-radial PWV across the four treatment groups were 0.24 m/s (95% CI: -0.45, 0.92 m/s) for placebo, 0.09 m/s (95% CI: -0.54, 0.73 m/s) for 600 IU/day group, -0.57 m/s (95% CI: -1.20, 0.07 m/s) for the 2,000 IU/day group, and -0.61 m/s (95% CI: -1.25, 0.02 m/s) for the 4,000 IU/day group., Conclusion: Arterial stiffness was improved by vitamin D3 supplementation in a dose-response manner in overweight African Americans with vitamin D deficiency.

Though still a topic of debate, the position that skeletal health is compromised with obesity has received support in the pediatric and adult literature. The limited data relating specifically to trabecular bone microarchitecture, however, have been relatively inconsistent. The aim of this pilot cross-sectional case-control study was to compare trabecular bone microarchitecture between obese (OB) and normal-weight (NW) late-adolescent females. A secondary aim was to compare diaphyseal cortical bone outcomes between these two groups. Twenty-four non-Hispanic white females, ages 18-19 years, were recruited into OB (n = 12) or NW (n = 12) groups based on pre-specified criteria for percent body fat (≥32 vs. <30, respectively), body mass index (>90th vs. 20th-79th, respectively), and waist circumference (≥90th vs. 25th-75th, respectively). Participants were also individually matched on age, height, and oral contraceptive use. Using magnetic resonance imaging, trabecular bone microarchitecture was assessed at the distal radius and proximal tibia metaphysis, and cortical bone architecture was assessed at the mid-radius and mid-tibia diaphysis. OB versus NW had lower apparent trabecular thickness (radius and tibia), higher apparent trabecular separation (radius), and lower apparent bone volume to total volume (radius; all P < 0.050). Some differences in radius and tibia trabecular bone microarchitecture were retained after adjusting for insulin resistance or age at menarche. Mid-radius and mid-tibia cortical bone volume and estimated strength were lower in the OB compared to NW after adjusting for fat-free soft tissue mass (all P < 0.050). These trabecular and cortical bone deficits might contribute to the increased fracture risk in obese youth.

Objectives: We used mediation models to examine the mechanisms underlying the relationships among physical fitness, sleep-disordered breathing (SDB), symptoms of depression, and cognitive functioning., Methods: We conducted a cross-sectional secondary analysis of the cohorts involved in the 2003-2006 project PLAY (a trial of the effects of aerobic exercise on health and cognition) and the 2008-2011 SMART study (a trial of the effects of exercise on cognition). A total of 397 inactive overweight children aged 7-11 received a fitness test, standardized cognitive test (Cognitive Assessment System, yielding Planning, Attention, Simultaneous, Successive, and Full Scale scores), and depression questionnaire. Parents completed a Pediatric Sleep Questionnaire. We used bootstrapped mediation analyses to test whether SDB mediated the relationship between fitness and depression and whether SDB and depression mediated the relationship between fitness and cognition., Results: Fitness was negatively associated with depression ( B = -0.041; 95% CI, -0.06 to -0.02) and SDB ( B = -0.005; 95% CI, -0.01 to -0.001). SDB was positively associated with depression ( B = 0.99; 95% CI, 0.32 to 1.67) after controlling for fitness. The relationship between fitness and depression was mediated by SDB (indirect effect = -0.005; 95% CI, -0.01 to -0.0004). The relationship between fitness and the attention component of cognition was independently mediated by SDB (indirect effect = 0.058; 95% CI, 0.004 to 0.13) and depression (indirect effect = -0.071; 95% CI, -0.01 to -0.17)., Conclusions: SDB mediates the relationship between fitness and depression, and SDB and depression separately mediate the relationship between fitness and the attention component of cognition.

Background: Associations between childhood vitamin K consumption and cardiac structure and function have not been investigated., Objective: We determined associations between phylloquinone (vitamin K-1) intake and left ventricular (LV) structure and function in adolescents., Methods: We assessed diet with three to seven 24-h recalls and physical activity (PA) by accelerometry in 766 adolescents (aged 14-18 y, 50% female, 49% black). Fat-free soft tissue (FFST) mass and fat mass were measured by dual-energy X-ray absorptiometry. LV structure [LV mass (g)/height (m)2.7 (LV mass index) and relative wall thickness] and function [midwall fractional shortening (MFS) and ejection fraction] were assessed by echocardiography. Associations were evaluated by comparing the LV structure and function variables across tertiles of phylloquinone intake. Prevalence and OR of LV hypertrophy (LV mass index >95th percentile for age and sex) were also assessed by phylloquinone tertiles., Results: The prevalence of LV hypertrophy progressively decreased across tertiles of phylloquinone intake (P-trend < 0.01). Multinomial logistic regression-adjusting for age, sex, race, Tanner stage, systolic blood pressure, FFST mass, fat mass, socioeconomic status, PA, and intakes of energy, fiber, calcium, vitamin C, vitamin D, and sodium-revealed that compared with the highest phylloquinone intake tertile (reference group), the adjusted OR for LV hypertrophy was 3.3 (95% CI: 1.2, 7.4) for those in the lowest phylloquinone intake tertile. When LV structure variables were compared across phylloquinone intake tertiles adjusting for the same covariates, there were significant linear downward trends for LV mass index (6.5% difference, tertile 1 compared with tertile 3) and relative wall thickness (9.2% difference, tertile 1 compared with tertile 3; both P-trend ≤ 0.02). Conversely, significant linear upward trends across phylloquinone intake tertiles were observed for MFS (3.4% difference, tertile 1 compared with tertile 3) and ejection fraction (2.6% difference, tertile 1 compared with tertile 3; both P-trend < 0.04)., Conclusion: Our adolescent data suggest that subclinical cardiac structure and function variables are most favorable at higher phylloquinone intakes., (© 2017 American Society for Nutrition.)

Background: Zinc is a micronutrient involved in the production of, and peripheral sensitivity to, pancreatic β cell-derived insulin. To our knowledge, the effect of zinc supplementation on insulin outcomes, and potential risk of diabetes, in otherwise healthy children in the United States has not been investigated. Objective: The objective of this study was to determine the influence of zinc supplementation on insulin outcomes in black and white girls in the early stages of adolescence. A secondary objective was to determine relations between baseline zinc concentrations and insulin outcomes. Methods: Healthy black and white girls aged 9-11 y were randomly assigned to daily supplementation of zinc (9 mg elemental Zn/d; n = 75; blacks: n = 35) or placebo ( n = 72; blacks: n = 32) for 4 wk. Fasting serum insulin, glucose, and C-peptide were assessed at baseline and at 4 wk. C-peptide and glucose values were used to calculate the computer model-derived homeostatic model assessment of insulin resistance (HOMA2-IR). Changes in outcome measures were compared by using repeated-measures, mixed-model ANOVA. Results: Baseline plasma zinc was not correlated with C-peptide ( r = -0.07), insulin ( r = -0.06), or HOMA2-IR ( r = -0.09) (all P > 0.05) after controlling for race and age. Treatment × time interactions for C-peptide and HOMA2-IR were not significant (both P > 0.05). Although the treatment × race × time interactions for C-peptide and HOMA2-IR were not significant (both P = 0.08), black girls who received the placebo experienced slight increases in C-peptide (15.7%) and HOMA2-IR (17.7%) ( P = 0.06). Conclusions: Four weeks of zinc supplementation had no effect on insulin outcomes in healthy black and white early-adolescent girls, although C-peptide and HOMA2-IR tended to increase in black girls who received placebo. Additional trials that are appropriately powered should further explore the effect of zinc on markers of diabetes risk, and whether race affects this relation. This trial was registered at clinicaltrials.gov as NCT01892098., Competing Interests: Author disclosures: AJL, JMK, NTJ, NKP, EML, AG, and RDL, no conflicts of interest., (© 2017 American Society for Nutrition.)

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (p Interaction  < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (β Indirect Effect  = 0.321, p < 0.001). However, this relationship was moderated in the children with high (β Indirect Effect  = 0.200, p < 0.001) versus normal (β Indirect Effect  = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Whole-body vibration (WBV) has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether WBV recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wild-type (WT) and leptin receptor-deficient (db/db) mice to daily treadmill exercise (TE) or WBV for 3 months. Body weights were analyzed and compared with WT and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following TE or WBV. Both interventions reduced body weight in db/db mice and normalized muscle fiber diameter. TE or WBV also attenuated adipocyte hypertrophy in visceral adipose tissue and reduced hepatic lipid content in db/db mice. Although the effects of leptin receptor deficiency on cortical bone structure were not eliminated by either intervention, exercise and WBV increased circulating levels of osteocalcin in db/db mice. In the context of increased serum osteocalcin, the modest effects of TE and WBV on bone geometry, mineralization, and biomechanics may reflect subtle increases in osteoblast activity in multiple areas of the skeleton. Taken together, these observations indicate that WBV recapitulates the effects of exercise on metabolism in type 2 diabetes.

Objective: To determine the association of birth weight with abdominal fat distribution and markers known to increase risk for cardiovascular disease and type 2 diabetes in adolescents., Study Design: In 575 adolescents aged 14-18 years (52% female, 46% black), birth weight was obtained by parental recall. Fasting blood samples were measured for glucose, insulin, lipids, adiponectin, leptin, and C-reactive protein. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed by magnetic resonance imaging., Results: When we compared markers of cardiometabolic risk across tertiles of birth weight, adjusting for age, sex, race, Tanner stage, physical activity, socioeconomic status, and body mass index, there were significant U-shaped trends for homeostasis model assessment of insulin resistance, leptin, and visceral adipose tissue (all Pquadratic < .05). A significant linear downward trend across tertiles of birth weight was observed for triglycerides (Plinear = .03). There were no differences in fasting glucose, blood pressure, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, adiponectin, C-reactive protein, or subcutaneous abdominal adipose tissue across tertiles of birth weight., Conclusions: Our data suggest that both low and high birth weights are associated with greater visceral adiposity and biomarkers implicated in insulin resistance and inflammation in adolescents., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Understanding of the influence of vitamin D deficiency on epigenome will provide novel insights into the chronic disease risk. We tested our hypotheses that 1) vitamin D deficiency is associated with global hypomethylation and this association may be race/ethnicity dependent; and 2) vitamin D supplementation will increase global DNA methylation level., Methods: A two-stage design, cross-sectional observation followed by a 16 week randomized, double- blinded, placebo-controlled trial (RCT) of vitamin D3 supplementation, was undertaken. Global DNA methylation level (percentage of 5-methylcytosine, %5-mC) was quantified using leukocyte DNA with the MethylFlashTM Methylated DNA Quantification kit (Epigentek). Global methylation data was obtained from 454 Caucasians and African Americans (42%) in the observation cohort and 58 African Americans with vitamin D deficiency in the dose responsive RCT., Results: In the cross-sectional study, African Americans had lower %5-mC than Caucasians (P = 0.04). A significant interaction was detected between plasma 25(OH)D and race on %5-mC (P = 0.05), as a positive association was observed between plasma 25(OH)D and %5-mC in African Americans (β = 0.20, p<0.01), but not in Caucasians (β = 0.03, p = 0.62). In the 16-week RCT, a dose-response benefit of vitamin D3 supplementation was observed for %5-mC, as indicated by a significant linear upward trend (-0.01 ± 0.01%, placebo; 0.11 ± 0.01%, ~600 IU/day; 0.30 ± 0.01%, ~2,000 IU/day; and 0.65 ± 0.01%, ~4,000 IU/day group; P-trend = 0.04)., Conclusions: Vitamin D deficiency is associated with global hypomethylation in African Americans. Vitamin D3 supplementation increases global DNA methylation in a dose-response manner in African Americans with vitamin D deficiency.

Context: IGF-1 promotes bone growth directly and indirectly through its effects on skeletal muscle. Insulin and IGF-1 share a common cellular signaling process; thus, insulin resistance may influence the IGF-1-muscle-bone relationship., Objective: We sought to determine the effect of insulin resistance on the muscle-dependent relationship between IGF-1 and bone mass in premenarcheal girls., Design, Setting, and Participants: This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years., Main Outcome Measures: Glucose, insulin, and IGF-1 were measured from fasting blood samples. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Fat-free soft tissue (FFST) mass and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry. Our primary outcome was BMC/height., Results: In our path model, IGF-1 predicted FFST mass (b = 0.018; P = .001), which in turn predicted BMC/height (b = 0.960; P < .001). IGF-1 predicted BMC/height (b = 0.001; P = .002), but not after accounting for the mediator of this relationship, FFST mass. The HOMA-IR by IGF-1 interaction negatively predicted FFST mass (b = -0.044; P = .034). HOMA-IR had a significant and negative effect on the muscle-dependent relationship between IGF-1 and BMC/height (b = -0.151; P = .047)., Conclusions: Lean body mass is an important intermediary factor in the IGF-1-bone relationship. For this reason, bone development may be compromised indirectly via suboptimal IGF-1-dependent muscle development in insulin-resistant children.

Background: Data have shown that healthy children and adolescents have an inadequate intake of zinc, an essential nutrient for growth. It is unclear whether zinc supplementation can enhance bone health during this rapid period of growth and development., Objective: The primary aim of this study was to determine the effect of zinc supplementation on biochemical markers of bone turnover and growth in girls entering the early stages of puberty. The secondary aim was to test moderation by race, body mass index (BMI) classification, and plasma zinc status at baseline., Methods: One hundred forty seven girls aged 9-11 y (46% black) were randomly assigned to a daily oral zinc tablet (9 mg elemental zinc; n = 75) or an identical placebo (n = 72) for 4 wk. Fasting plasma zinc, procollagen type 1 amino-terminal propeptide (P1NP; a bone formation marker), carboxy-terminal telopeptide region of type 1 collagen (ICTP; a bone resorption marker), and insulin-like growth factor I (IGF-I) were assessed at baseline and post-test. Additional markers of bone formation (osteocalcin) and resorption (urinary pyridinoline and deoxypyridinoline) were also measured., Results: Four weeks of zinc supplementation increased plasma zinc concentrations compared with placebo [mean change, 1.8 μmol/L (95% CI: 1.0, 2.6) compared with 0.2 μmol/L (95% CI: -0.3, 0.7); P < 0.01]. Zinc supplementation also increased serum P1NP concentrations compared with placebo [mean change, 23.8 μmol/L (95% CI: -14.9, 62.5) compared with -31.0 μmol/L (95% CI: -66.4, 4.2); P = 0.04). There was no effect from zinc supplementation on osteocalcin, ICTP, pyridinoline, deoxypyridinoline, or IGF-I. There was no moderation by race, BMI classification, or plasma zinc status at baseline., Conclusions: Our data suggest that 4 wk of zinc supplementation increases bone formation in premenarcheal girls. Further studies are needed to determine whether supplemental zinc can improve childhood bone strength. This trial was registered at clinicaltrials.gov as NCT01892098., (© 2015 American Society for Nutrition.)

Background/objectives: Telomere shortening has an important role in cellular aging. However, the impact of high sodium intake, an important risk factor of age-related diseases, on telomere shortening remains unknown. Therefore, we examined the relationship between high dietary sodium intake and leukocyte telomere length (LTL), particularly in the context of obesity, as obesity increases salt sensitivity., Subjects/methods: LTL was determined by a quantitative polymerase chain reaction method in 766 adolescents aged 14-18 years (50% females, 49% African Americans). Dietary sodium intake was assessed by seven independent 24-h dietary recalls. We divided the sample into low sodium (mean 2388±522 mg per day) or high sodium groups (mean 4142±882 mg per day) based on the median value (3280.9 mg per day)., Results: In the entire cohort, there was no significant association between sodium intake and LTL (r=-0.05, P=0.24). However, there was a significant interaction between sodium intake and obesity status (P=0.049). Further multiple linear regression analyses revealed that higher dietary sodium intake was associated with shorter LTL in the overweight/obese group (body mass index ⩾85th percentile, β=-0.37, P=0.04), but not in the normal-weight group (β=0.01, P=0.93) after adjusting for multiple confounding factors. In the overweight/obese group, LTL was significantly shorter in the high sodium intake subjects vs low sodium intake subjects (1.24±0.22 vs. 1.32±0.20, P=0.02), but not the normal-weight group (1.29±0.24 vs 1.30±0.24, P=0.69)., Conclusions: Higher dietary sodium intake is associated with shorter telomere length in overweight and obese adolescents.

Osteoporosis and obesity are both major public health concerns. It has long been considered that these are distinct disorders rarely found in the same individual; however, emerging evidence supports an important interaction between adipose tissue and the skeleton. Whereas overweight per se may augment bone strength, animal studies suggest that the metabolic impairment that accompanies obesity is detrimental to bone. Obesity during childhood, a critical time for bone development, likely has profound and lasting effects on bone strength and fracture risk. This notion has received little attention in children and results are mixed, with studies reporting that bone strength development is enhanced or impaired by obesity. Whether obesity is a risk factor for osteoporosis or childhood bone health, in general, remains an important clinical question. Here, we will focus on clarifying the controversial relationships between childhood obesity and bone strength development, and provide insights into potential mechanisms that may regulate the effect of excess adiposity on bone., (Published by Elsevier Ireland Ltd.)

Background: A critical need exists to better understand the physiological sequel of vitamin D supplementation in obese individuals and African Americans. The aim was to comprehensively evaluate dose- and time-responses of a panel of vitamin D biomarkers to vitamin D supplements in this population., Methods: We conducted a 16-week randomized, double-blinded, and placebo-controlled clinical trial. Seventy overweight/obese African Americans (age 13-45 years, 84 % females) with 25-hydroxyvitamin D [25(OH)D] concentrations ≤20 ng/mL were randomly assigned to receive a supervised monthly oral vitamin D3 of 18,000 IU (~600 IU/day, n = 17), 60,000 IU (~2000 IU/day, n = 18), 120,000 IU (~4000 IU/day, n = 18), or placebo (n = 17)., Results: There were significant dose- and time-responses of circulating 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)2D], and intact parathyroid hormone (iPTH), but not fibroblast growth factor-23 (FGF-23), phosphorus and urine calcium to the vitamin D supplements. The mean 25(OH)D concentrations in the 2000 IU and 4000 IU groups reached ≥30 ng/mL as early as 8-weeks and remained at similar level at 16-weeks. The increase of 25(OH)D was significantly higher in the 4000 IU group than all the other groups at 8-weeks. The increase of 1,25(OH)2D was significantly higher in the 2000 IU and 4000 IU groups than the placebo at 8-weeks. Only the 4000 IU compared to the placebo significantly reduced iPTH at 8- and 16-weeks., Conclusions: Our RCT, for the first time, comprehensively evaluated time- and dose- responses of vitamin D supplementation in overweight/obese African Americans with suboptimal vitamin D status. Circulating 25(OH)D, 1,25(OH)2D, and iPTH, but not FGF-23, phosphorus and urine calcium, respond to vitamin D supplementation in a time- and dose-response manner. By monthly dosing, 2000 IU appears to be sufficient in achieving a 25(OH)D level of 30 ng/mL in this population. However, importantly, 4000 IU, rather than 2000 IU, seems to suppress iPTH. If replicated, these data might be informative in optimizing vitamin D status and providing individualized dosing recommendation in overweight/obese African Americans., Trial Registration: ClinicalTrials.gov number: NCT01583621, Registered on April 3, 2012.

Assessment of physical activity in clinical bone studies is essential. Two bone-specific physical activity scoring methods, the Bone Loading History Questionnaire (BLHQ) and Bone-Specific Physical Activity Questionnaire (BPAQ), have shown correlations with bone density and geometry, but not architecture. The purpose of this study was to determine relationships between physical activity scoring methods and bone architecture in non-Hispanic white adolescent females (N = 24; 18-19 years of age). Bone loading scores (BLHQ [hip and spine] and past BPAQ) and energy expenditure (7-day physical activity recall) were determined from respective questionnaires. Estimates of trabecular and cortical bone architecture at the nondominant radius and tibia were assessed via magnetic resonance imaging. Total body and regional areal bone mineral density (aBMD), as well as total body fat mass and fat-free soft tissue (FFST) mass were assessed via dual energy X-ray absorptiometry. Pearson's correlations and partial correlations adjusting for height, total body fat mass, and FFST were performed. Hip BLHQ scores were correlated with midtibia cortical volume (r = .43; p = .03). Adjusted hip and spine BLHQ scores were correlated with all midtibia cortical measures (r = .50-0.58; p < .05) and distal radius apparent trabecular number (r = .46-0.53; p < .05). BPAQ scores were correlated with all midtibia cortical (r = .41-0.51; p < .05) and most aBMD (r = .47-0.53; p < .05) measures. Energy expenditure was inversely associated with femoral neck aBMD only after statistical adjustment (r = .49, p < .05). These data show that greater load-specific physical activity scores, but not energy expenditure, are indicative of greater midtibia cortical bone quality, thus supporting the utility of these instruments in musculoskeletal research.

Context: Although animal studies suggest that adenovirus 36 (Ad36) infection is linked to obesity and systemic inflammation, human data are scant and equivocal., Objective: Associations of Ad36 infection with total body adiposity and inflammatory-related markers were determined in 291 children aged 9-13 years (50% female, 49% black)., Design: Fasting blood samples were measured for presence of Ad36-specific antibodies and TNF-α, IL-6, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). Fat mass and fat-free soft tissue mass were measured by dual-energy X-ray absorptiometry., Results: The overall prevalence of Ad36 seropositivity [Ad36(+)] was 42%. There was a higher percentage of Ad36(+) children in the highest tertiles of TNF-α and IL-6 compared with their respective middle and lowest tertiles (both P < .03). There was also a trend toward a higher prevalence of Ad36(+) children in the highest tertile of VEGF compared with tertiles 1 and 2 (P = .05). Multinomial logistic regression, adjusting for age, race, sex, and fat-free soft tissue mass, revealed that compared with children with the lowest TNF-α, IL-6, and VEGF levels (tertile 1), the adjusted odds ratios for Ad36(+) were 2.2 [95% confidence interval (CI) 1.2-4.0], 2.4 (95% CI 1.4-4.0), and 1.8 (95% CI 1.0-3.3), respectively, for those in the highest TNF-α, IL-6, and VEGF levels (tertile 3). No association was observed between Ad36(+) and greater levels of fat mass or MCP-1 (all P > .05)., Conclusions: In children, our data suggest that Ad36(+) may be associated with biomarkers implicated in inflammation but not with greater levels of fat mass.

Objectives: To determine the relationships of sodium intake with adiposity and inflammation in healthy adolescents., Methods: A cross-sectional study involved 766 healthy white and African American adolescents aged 14 to 18 years. Dietary sodium intake was estimated by 7-day 24-hour dietary recall. Percent body fat was measured by dual-energy x-ray absorptiometry. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed using magnetic resonance imaging. Fasting blood samples were measured for leptin, adiponectin, C-reactive protein, tumor necrosis factor-α, and intercellular adhesion molecule-1., Results: The average sodium intake was 3280 mg/day. Ninety-seven percent of our adolescents exceeded the American Heart Association recommendation for sodium intake. Multiple linear regressions revealed that dietary sodium intake was independently associated with body weight (β = 0.23), BMI (β = 0.23), waist circumference (β = 0.23), percent body fat (β = 0.17), fat mass (β = 0.23), subcutaneous abdominal adipose tissue (β = 0.25), leptin (β = 0.20), and tumor necrosis factor-α (β = 0.61; all Ps < .05). No relation was found between dietary sodium intake and visceral adipose tissue, skinfold thickness, adiponectin, C-reactive protein, or intercellular adhesion molecule-1. All the significant associations persisted after correction for multiple testing (all false discovery rates < 0.05)., Conclusions: The mean sodium consumption of our adolescents is as high as that of adults and more than twice the daily intake recommended by the American Heart Association. High sodium intake is positively associated with adiposity and inflammation independent of total energy intake and sugar-sweetened soft drink consumption.

Adipose tissue is a known source of proinflammatory cytokines in obese humans and animal models, including the db/db mouse, in which obesity arises as a result of leptin receptor insensitivity. Inflammatory cytokines induce cognitive deficits across numerous conditions, but no studies have determined whether obesity-induced inflammation mediates synaptic dysfunction. To address this question, we used a treadmill training paradigm in which mice were exposed to daily training sessions or an immobile belt, with motivation achieved by delivery of compressed air on noncompliance. Treadmill training prevented hippocampal microgliosis, abolished expression of microglial activation markers, and also blocked the functional sensitization observed in isolated cells after ex vivo exposure to lipopolysaccharide. Reduced microglial reactivity with exercise was associated with reinstatement of hippocampus-dependent memory, reversal of deficits in long-term potentiation, and normalization of hippocampal dendritic spine density. Because treadmill training evokes broad responses not limited to the immune system, we next assessed whether directly manipulating adiposity through lipectomy and fat transplantation influences inflammation, cognition, and synaptic plasticity. Lipectomy prevents and fat transplantation promotes systemic and central inflammation, with associated alterations in cognitive and synaptic function. Levels of interleukin 1β (IL1β) emerged as a correlate of adiposity and cognitive impairment across both the treadmill and lipectomy studies, so we manipulated hippocampal IL1 signaling using intrahippocampal delivery of IL1 receptor antagonist (IL1ra). Intrahippocampal IL1ra prevented synaptic dysfunction, proinflammatory priming, and cognitive impairment. This pattern supports a central role for IL1-mediated neuroinflammation as a mechanism for cognitive deficits in obesity and diabetes.

Human clinical trials targeted at preventing gains in body weight using soy protein and isoflavones are limited to adults and yield conflicting results. We hypothesized that daily intake of soy protein/isoflavones would attenuate gains in body weight to a greater extent than a casein-based control in 18 to 19 year-old females. To test this hypothesis, we conducted a randomized, double blind, placebo-controlled trial over 16 weeks to examine the effects of a soy protein/isoflavone-based meal replacement (experimental group) versus a casein-based meal replacement (control group) on body weight and body composition variables in female college freshmen (N = 120). Fat mass (FM), fat-free soft tissue mass (FFST), and percent body fat (%BF) were measured using dual energy X-ray absorptiometry (DXA; Delphi A). Repeated measures mixed models were used to determine the effects of treatment on anthropometric and body composition variables (body weight, waist circumference, FM, FFST, and %BF). No significant group×time interactions were observed, even when body mass index was controlled for in the analysis. Over 16 weeks, body weight, FM, FFST, and %BF significantly increased in both groups (P < .05). Our findings show that female college freshmen gained a significant amount of weight over the course of the 16-week study. Gains in body weight and FM were similar among participants assigned to the soy protein/isoflavone- and the casein-based meal replacements. Future research is warranted to determine the effects of soy protein/isoflavone- and casein-based meal replacements versus a non-intervention (i.e., non-protein based) control., (© 2013.)

Background: Metabolic abnormalities in obesity can overstimulate the renal epithelial sodium channel (ENaC) and subsequently lead to blood pressure (BP) elevation. Prostasin, a membrane-bound/secretive serine protease, is thought to activate ENaC via the proteolytic cleavage of the channel. Our specific aim was to explore whether there is a relationship between adiposity and urinary prostasin excretion at the population level., Methods: In 271 African-American adolescents, urinary prostasin concentrations were determined by enzyme-linked immunosorbent assay and normalized by urinary creatinine., Results: Urinary prostasin excretion increased in the overweight/obese group (n = 110, 38.2 ± 4.0 ng/mg) vs. the normal-weight group (n = 161, 20.7 ± 1.2 ng/mg, P = 0.03). Urinary prostasin excretion was significantly correlated with BMI percentiles (r = 0.14, P = 0.02), waist circumference (r = 0.13, P = 0.05), total body fat mass (r = 0.20, P < 0.01), and percentage body fat (r = 0.23, P < 0.01). Urinary prostasin excretion was also correlated with plasma aldosterone (r = 0.11, P = 0.05) and systolic BP (SBP; r = 0.15, P = 0.02), but the significances disappeared after adjustment of any of the adiposity variables., Conclusion: Our data for the first time suggest that adiposity plays a role in urinary prostasin excretion, and its associations with aldosterone and BP appear to be modulated by adiposity. Whether urinary prostasin excretion is a biomarker/mechanism underlying obesity-related hypertension deserves further investigations.

Context: Animal studies indicate that osteocalcin (OC), particularly the undercarboxylated isoform (unOC), affects insulin sensitivity and secretion, but definitive data from humans are lacking., Objective: The objectives of the study were to determine whether total OC and unOC are independently associated with insulin sensitivity and β-cell response in overweight/obese adults; whether glucose tolerance status affects these associations; and whether the associations are independent of bone formation, as reflected in procollagen type 1 amino propeptide (P1NP)., Design, Setting, and Participants: This was a cross-sectional study conducted at a university research center involving 63 overweight/obese adults with normal (n = 39) or impaired fasting glucose (IFG; n = 24)., Main Outcome Measures: Serum concentrations of total/undercarboxylated OC and P1NP were assessed by RIA; insulin sensitivity was determined by iv glucose tolerance test (S(I)-IVGTT), liquid meal test (S(I) meal), and homeostasis model assessment of insulin resistance; β-cell response to glucose [basal β-cell response to glucose; dynamic β-cell response to glucose; static β-cell response to glucose; and total β-cell response to glucose] was derived using C-peptide modeling of meal test data; and intraabdominal adipose tissue was measured using computed tomography scanning., Results: Multiple linear regression, adjusting for intraabdominal adipose tissue and P1NP, revealed that total OC was positively associated with S(I)-iv glucose tolerance test (P < .01) in the total sample. OC was not associated with S(I) meal or homeostasis model assessment of insulin resistance. In participants with IFG, unOC was positively associated with static β-cell response to glucose and total β-cell response to glucose (P < .05), independent of insulin sensitivity., Conclusions: In overweight/obese individuals, total OC may be associated with skeletal muscle but not hepatic insulin sensitivity. unOC is uniquely associated with β-cell function only in individuals with IFG. Further research is needed to probe the causal inference of these relationships and to determine whether indirect nutrient sensing pathways underlie these associations.

Adenovirus 36 (Ad36) is the only adenovirus to date that has been linked with obesity in humans. Our previous studies in late-adolescent females suggest that excess weight in the form of fat mass is associated with lower cortical bone strength. The purpose of this study was to assess the relationship between Ad36-specific antibodies, adiposity, and bone strength in our sample of late-adolescent females. A cross-sectional study of 115 females aged 18 to 19 years was performed. Participants were classified according to adiposity by dual-energy X-ray absorptiometry (body fat percentage as normal-fat [ < 32% body fat; n = 93] or high-fat [ ≥ 32% body fat; n = 22]), and according to the presence of Ad36-specific neutralizing antibodies. Peripheral quantitative computed tomography measured bone parameters at the 4% (trabecular bone) and 20% (cortical bone) site, and muscle cross-sectional area (MCSA) at the 66% site, from the distal metaphyses of the radius and the tibia. Bone strength was determined from volumetric bone mineral density and bone geometry to calculate bone strength index (BSI; trabecular site) and polar strength-strain index (SSI; cortical site). After adjustment for MCSA and limb length, radial SSI was lower in Ad36+  versus Ad36- subjects from the high-fat group (p < 0.03), but not the normal-fat group. No significant differences were observed between groups in tibial SSI or BSI. These data support an association of adiposity and cortical bone strength at the radius with the presence of neutralizing antibodies to Ad36 in late-adolescent females., (Copyright © 2013 American Society for Bone and Mineral Research.)

Context: The link between adolescent fiber consumption, inflammation, and body fat distribution has not been investigated., Objective: This study investigated associations of dietary fiber intake with inflammatory-related biomarkers and robust measures of total and central adiposity in a sample of 559 adolescents aged 14-18 yr (49% female, 45% Black)., Methods: Fasting blood samples were measured for leptin, adiponectin, resistin, C-reactive protein, and fibrinogen. Diet was assessed with four to seven 24-h recalls, and physical activity was determined by accelerometry. Fat-free soft tissue mass and fat mass were measured by dual-energy x-ray absorptiometry. Visceral adipose tissue was assessed using magnetic resonance imaging., Results: Multiple linear regression, adjusting for age, race, Tanner stage, fat-free soft tissue mass, energy intake, and physical activity, revealed that dietary fiber intake was inversely associated with fat mass and serum leptin in males (all P < 0.03) but not in females. In both genders, dietary fiber intake was negatively associated with visceral adipose tissue, plasma C-reactive protein, and plasma fibrinogen and positively associated with plasma adiponectin (all P < 0.05). No relations were found between dietary fiber intake and plasma resistin in either males or females., Conclusion: Our adolescent data suggest that greater consumption of dietary fiber is associated with lower visceral adiposity and multiple biomarkers implicated in inflammation.

Objective: Low vitamin D status is common among healthy black and white adolescents residing at southern U.S. latitudes with a year-round sunny climate. Thus we aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk factors in this population., Research Design and Methods: 25(OH)D concentrations were measured with liquid chromatography tandem mass spectroscopy in 701 girls and boys (14-18 years old, 54% blacks, 49% females). Cardiometabolic risk was indexed by adipokines, inflammatory markers, fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and blood pressure (BP)., Results: Controlling for age, sex, race, sexual maturation, season, physical activity, and percent body fat, 25(OH)D concentrations were significantly correlated with adiponectin (r = 0.06, P = 0.05), leptin (r = -0.32, P < 0.01), fibrinogen (r = -0.05, P = 0.03), glucose (r = -0.16, P = 0.02), HOMA-IR (r = -0.17, P < 0.01), HDL cholesterol (r = 0.14, P = 0.02), systolic BP (r = -0.10, P = 0.02), and diastolic BP (r = -0.21, P < 0.01). When 25(OH)D concentrations were stratified into increasing tertiles, there were significant linear upward trends for adiponectin (P = 0.01) and HDL cholesterol (P = 0.04), but significant linear down trends for glucose (P < 0.01), HOMA-IR (P < 0.01), and systolic BP (P < 0.01), after adjusting for the above covariates., Conclusions: Circulating 25(OH)D concentrations are associated with various adverse cardiometabolic risk factors, independent of adiposity. Clinical trials addressing the effects of vitamin D supplementation on cardiometabolic risk are warranted in adolescents irrespective of their geographical regions.

Though adolescents consume more fructose than any other age group, the relationship between fructose consumption and markers of cardiometabolic risk has not been established in this population. We determined associations of total fructose intake (free fructose plus one-half the intake of free sucrose) with cardiometabolic risk factors and type of adiposity in 559 adolescents aged 14-18 y. Fasting blood samples were measured for glucose, insulin, lipids, adiponectin, and C-reactive protein. Diet was assessed with 4-7 24-h recalls and physical activity (PA) was determined by accelerometry. Fat-free soft tissue (FFST) mass and fat mass were measured by DXA. The s.c. abdominal adipose tissue (SAAT) and visceral adipose tissue (VAT) were assessed using MRI. Multiple linear regression, adjusting for age, sex, race, Tanner stage, FFST mass, fat mass, PA, energy intake, fiber intake, and socioeconomic status, revealed that fructose intake was associated with VAT (β = 0.13; P = 0.03) but not SAAT (P = 0.15). Significant linear upward trends across tertiles of fructose intake were observed for systolic blood pressure, fasting glucose, HOMA-IR, and C-reactive protein after adjusting for the same covariates (all P-trend < 0.04). Conversely, significant linear downward trends across tertiles of fructose intake were observed for plasma HDL-cholesterol and adiponectin (both P-trend < 0.03). When SAAT was added as a covariate, these trends persisted (all P-trend < 0.05). However, when VAT was included as a covariate, it attenuated these trends (all P-trend > 0.05). In adolescents, higher fructose consumption is associated with multiple markers of cardiometabolic risk, but it appears that these relationships are mediated by visceral obesity.

Context: Although animal studies suggest that it is the uncarboxylated rather than carboxylated form of osteocalcin that affects glucose homeostasis, the human data are scant and equivocal., Objective: This study investigated associations of uncarboxylated and carboxylated forms of osteocalcin with insulin sensitivity and β-cell function in 140 overweight prepubertal children (43% female, 46% black, 84% obese) with normal glucose levels (n = 99) and prediabetes (n = 41)., Methods: An oral glucose tolerance test was used to identify prediabetes and for measurement of insulin sensitivity (Matsuda index), β-cell function [oral glucose tolerance test derived insulinogenic index and disposition index (DI(OGTT))] and uncarboxylated and carboxylated forms of osteocalcin. Visceral adipose tissue (VAT) was assessed using magnetic resonance imaging., Results: After controlling for age, sex and race, lower uncarboxylated osteocalcin concentrations, Matsuda index, insulinogenic index, and DI(OGTT) and higher VAT levels were found in the prediabetes vs. normal-glucose group (all P < 0.03). Carboxylated osteocalcin levels were not different between groups. Multiple linear regression adjusting for age, sex, race, and VAT revealed that uncarboxylated osteocalcin was associated with insulinogenic index and DI(OGTT) (β = 0.34, 0.36, respectively, both P < 0.04) in the prediabetes group but not the normal-glucose group. In both the normal-glucose and prediabetes groups, carboxylated osteocalcin was associated with insulin sensitivity (β = 0.26, 0.47, respectively, both P < 0.02)., Conclusions: These data suggest that the lower uncarboxylated osteocalcin concentrations found in children with prediabetes may be associated with β-cell dysfunction. In addition, our findings between carboxylated osteocalcin and insulin sensitivity suggest that carboxylated osteocalcin plays a role in human glucose homeostasis.

Objective: To compare bone mass between overweight adolescents with and without cardiometabolic risk factors (CMR). Associations of bone mass with CMR and adiposity were also determined., Study Design: Adolescents (aged 14 to 18 years) who were overweight were classified as healthy (n = 55), having one CMR (1CMR; n = 46), or having two or more CMR (≥2CMR; n = 42). CMRs were measured with standard methods and defined according to pediatric definitions of metabolic syndrome. Total body bone mass, fat mass, and fat-free soft tissue mass were measured with dual-energy X-ray absorptiometry. Visceral adipose tissue and subcutaneous abdominal adipose tissue were assessed with magnetic resonance imaging., Results: After controlling for age, sex, race, height, and fat-free soft tissue mass, the healthy group had 5.4% and 6.3% greater bone mass than the 1CMR and ≥2CMR groups, respectively (both P values <.04). With multiple linear regression, adjusting for the same co-variates, visceral adipose tissue (β = -0.22), waist circumference (β = -0.23), homeostasis model assessment of insulin resistance (β = -0.23), and high-density lipoprotein cholesterol level (β = 0.22) were revealed to be associated with bone mass (all P values <.04). There was a trend toward a significant inverse association between bone mass and fasting glucose level (P = .056). No relations were found between bone mass and fat mass, subcutaneous abdominal adipose tissue, blood pressure, or triglyceride level., Conclusion: Being overweight with metabolic abnormalities, particularly insulin resistance, low high-density lipoprotein cholesterol level, and visceral adiposity, may adversely influence adolescent bone mass., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Unlabelled: Despite adolescent black females experiencing the highest rates of obesity, the effect of excess fat mass on bone structure and strength in this population is unknown. Our findings in postadolescent black females suggest that excess weight in the form of fat mass may adversely influence cortical bone structure and strength., Introduction: Although adolescent obesity has been associated with reduced bone structure and strength in white females, this relationship has not been studied in adolescent black females, a population experiencing the highest rates of obesity. Our objective was to compare bone structure and strength between postadolescent black females with normal and high levels of adiposity., Methods: Black females with ≤ 32% body fat were classified as normal body fat (NF; n = 33, aged 19.3 ± 1.3 years); females exceeding this cutoff were classified as high body fat (HF; n = 15, aged 19.0 ± 1.1 years). Using peripheral quantitative computed tomography, tibial and radial bones were scanned at the 4% (trabecular) and 20% (cortical) sites from the distal metaphyses. Fat-free soft-tissue mass (FFST) and %body fat were assessed by dual-energy X-ray absorptiometry., Results: After controlling for either FFST or body weight, the HF vs. NF group had lower total cross-sectional area (CSA; 9-17%), cortical CSA (6-15%), and strength-strain index (SSI; 13-24%) at the cortical site of the tibia (all p < 0.05). At the cortical site of the radius, the HF vs. NF group had lower total CSA (14%, p = 0.03), cortical CSA (9%, p = 0.04), and SSI (15%, p = 0.07) after control for body weight. There were no group differences in either the FFST-adjusted cortical bone values at the radius or in the trabecular bone parameters (body weight- or FFST-adjusted) at the tibia and radius., Conclusions: Consistent with our adiposity and bone data in late-adolescent white females, our findings in black females entering adulthood also suggest that obesity may adversely influence cortical bone strength.

Few childhood studies have investigated racial differences in volumetric bone mineral density (vBMD), bone geometry, and bone strength indices measured by three-dimensional bone imaging. The purpose of this study was to compare trabecular and cortical bone parameters at the radius and tibia between late adolescent white and black females using peripheral quantitative computed tomography (QCT). White (n = 25) and black females (n = 25), 18-19 years of age, were pair-matched for age, height, and fat-free soft tissue mass. Peripheral QCT scans were obtained at the 4% (trabecular bone), 20% (cortical bone), and 66% [muscle cross-sectional area (CSA)] sites from the distal metaphyses. Bone strength was determined from vBMD and bone geometry to calculate bone strength index (BSI; trabecular site) and polar strength-strain index (SSI; cortical site). Radial SSI was not different between groups; however, blacks had greater radial BSI (P = 0.02) than whites. After adjustment for the longer forearm in blacks, the greater radial BSI in blacks no longer remained. At the tibia, blacks versus whites had greater bone strength at the trabecular and cortical bone sites (BSI, P = 0.03; SSI, P = 0.04, respectively). When controlling for differences in tibial length and muscle CSA, the higher estimates of bone strength persisted in blacks versus whites (BSI, P = 0.01; SSI, P = 0.02). Our data suggest that when differences in body size are considered, late adolescent black versus white females have a stronger bone profile, due to greater bone geometry and vBMD, at the trabecular and cortical regions of the tibia but not at the radius.

Context: The extent to which 25-hydroxyvitamin D [25(OH)D] and IGF-I influence bone mineral content (BMC) accrual from early to mid-puberty is unclear. OBJECTIVE, SETTING, AND PARTICIPANTS: This study sought to determine relationships among 25(OH)D, IGF-I, and BMC in community-dwelling prepubertal females (n = 76; aged 4-8 yr at baseline) over a period of up to 9 yr., Design: The hypothesis that changes in IGF-I vs. 25(OH)D are more strongly associated with BMC accrual was formulated after data collection. 25(OH)D and IGF-I were log-transformed and further adjusted using two-way ANOVA for differences in season and race. Linear mixed modeling (including a random subject-specific intercept and a random subject-specific slope on age) was employed to analyze the proportion of variance the transformed 25(OH)D and IGF-I variables explained for the bone outcomes., Results: IGF-I was more strongly associated with BMC accrual than 25(OH)D at the total body (R(2) = 0.874 vs. 0.809), proximal femur (R(2) = 0.847 vs. 0.771), radius (R(2) = 0.812 vs. 0.759), and lumbar spine (R(2) = 0.759 vs. 0.698). The rate of BMC accrual was positively associated with changes in IGF-I but negatively associated with 25(OH)D. When IGF-I and 25(OH)D were included in the same regression equation, 25(OH)D did not have a significant predictive effect on BMC accrual above and beyond that of IGF-I., Conclusions: These prospective data in early adolescent females indicate that both 25(OH)D and IGF-I have a significant impact on bone mineral accrual; however, the positive association of IGF-I and BMC accrual is greater than the negative association of 25(OH)D and BMC accrual.

Childhood studies of the fat-bone relationship are conflicting, possibly reflecting the influence of metabolic abnormalities in some but not all obese children. Bone mass was compared between prepubertal overweight children with (n = 41) and without (n = 99) prediabetes. Associations of bone mass with measures of total and central adiposity, glucose intolerance, insulin sensitivity, lipid profile, systemic inflammation, and osteocalcin also were determined. In 140 overweight children aged 7 to 11 years, an oral glucose tolerance test was used to identify those with prediabetes and for determination of glucose, 2-hour glucose, glucose area under the curve (AUC), insulin, 2-hour insulin, and insulin AUC. Blood samples also were assessed for lipids, C-reactive protein, and osteocalcin. Total-body bone mineral content (BMC), fat-free soft tissue mass (FFST), and fat mass (FM) were measured by dual-energy X-ray absorptiometry (DXA). Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) were assessed using MRI. Total-body BMC was 4% lower in overweight children with prediabetes than in those without prediabetes after controlling for sex, race, height, and weight (p = .03). In the total sample, FM was positively related with BMC (β = 0.16, p = .01) after adjusting for sex, race, height, and FFST. However, VAT (β = -0.13, p = .03) and SAAT (β = -0.34, p = .02) were inversely associated with BMC after controlling for sex, race, height, FFST, FM, and SAAT or VAT. No significant associations were found between BMC and the biochemical measurements. Prepubertal overweight children with prediabetes may be at risk for poor skeletal development. In addition, it appears that greater levels of central rather than total adiposity may be deleterious for developing bone., (Copyright © 2010 American Society for Bone and Mineral Research.)

Context: Vitamin D insufficiency/deficiency is commonly observed in black youth., Objective: The aim was to determine 25-hydroxyvitamin D [25(OH)D] in response to 2000 IU vitamin D supplementation over time; to evaluate the relation between 25(OH)D concentrations and total body fat mass by dual-energy x-ray absorptiometry; and to determine whether vitamin D supplementation improves arterial stiffness measured by pulse wave velocity (PWV)., Design: We conducted a randomized, blinded, controlled clinical trial., Setting and Participants: Forty-nine normotensive black boys and girls, aged 16.3 ± 1.4 yr, were randomly assigned to either the control group (400 IU/d; n = 24) or the experimental group (2000 IU/d; n = 25)., Results: Plasma 25(OH)D values at baseline and at 4, 8, and 16 wk were 34.0 ± 10.6, 44.9 ± 9.4, 51.2 ± 11.1, and 59.8 ± 18.2 nmol/liter, respectively, for the control group; and 33.1 ± 8.7, 55.0 ± 11.8, 70.9 ± 22.0, and 85.7 ± 30.1 nmol/liter, respectively, for the experimental group. The experimental group vs. the control group reached significantly higher 25(OH)D concentrations at 8 and 16 wk, respectively. Partial correlation analyses indicated that total body fat mass at baseline was significantly and inversely associated with 25(OH)D concentrations in response to the 2000-IU supplement across time. Furthermore, carotid-femoral PWV increased from baseline (5.38 ± 0.53 m/sec) to posttest (5.71 ± 0.75 m/sec) in the control group (P = 0.016), whereas in the experimental group carotid-femoral PWV decreased from baseline (5.41 ± 0.73 m/sec) to posttest (5.33 ± 0.79 m/sec) (P = 0.031)., Conclusion: Daily 2000 IU vitamin D supplementation may be effective in optimizing vitamin D status and counteracting the progression of aortic stiffness in black youth. Plasma 25(OH)D concentrations in response to the 2000 IU/d supplementation are negatively modulated by adiposity.

Background: Whereas excess adiposity is presumed to be advantageous for the skeleton, studies investigating relations between bone strength and fat during youth have been equivocal., Objectives: Relations of percentage body fat (BF) and bone strength indexes were assessed in late adolescent females, taking into consideration surrogates of muscle force [ie, muscle cross-sectional area (MCSA) and bone length]. Bone measurements in the normal- and high-fat groups were also compared., Design: Late adolescent females (n = 115; aged 18.2 +/- 0.4 y) participated in this cross-sectional study. Fat-free soft tissue mass, fat mass, and percentage BF were measured with the use of dual-energy X-ray absorptiometry. Tibial and radial peripheral quantitative computed tomography measurements were taken at the 4% (trabecular bone), 20% (cortical bone), and 66% (for measurement of MCSA) sites from the distal metaphyses., Results: Percentage BF was inversely related to radial cortical bone area, total bone cross-sectional area (CSA), cortical bone mineral content (BMC), periosteal circumference, and strength-strain index (SSI) (20% site; all P < 0.05). After control for MCSA and limb length, negative relations remained between percentage BF and radial measurements and were also observed at the tibia (20% site). Unadjusted bone measures were not different between groups. After control for MCSA, the high- compared with the normal-fat group had lower bone measures at the 20% site (cortical bone area and cortical BMC at the tibia, total bone CSA at the radius, and SSI at both the tibia and radius; P < 0.05 for all)., Conclusion: Excess weight in the form of fat mass does not provide additional benefits, and may potentially be negative, for adolescent bone.

Introduction: If higher bone gains acquired from weight-bearing sports during growth persist into old age, the residual benefits could delay or even prevent osteoporotic fractures. The purpose of this study was to determine if the higher areal bone mineral density (aBMD) observed 15 years after competitive training and competition in former female college artistic gymnasts (GYM) compared with controls (CON) is maintained nine years later in this same cohort approaching menopause. In this 9-year follow-up, aBMD changes were also compared between GYM (n=16; aged 45.3+/-3.3 years) and CON (n=13; aged 45.4+/-3.8 years)., Methods: Total body, lumbar spine, proximal femur, femoral neck, leg, and arm aBMD were assessed at baseline and follow-up using dual-energy X-ray absorptiometry (DXA), (Hologic QDR-1000W). GYM had higher aBMD at all sites at follow-up (P<0.05; eta (2)>0.14)., Results: While there were no significant differences between groups for percent changes in aBMD at the total body, lumbar spine, total proximal femur, femoral neck, and arm, the change in leg aBMD was significantly different between GYM and CON (P=0.05; eta (2)=0.14)., Conclusions: Former female college artistic gymnasts maintained significantly higher aBMD than controls 24 years after retirement from gymnastics training and competition. This study provides greater insight into the effects of past athletic participation on skeletal health in women approaching menopause.

Relapse is an important clinical and research problem in the addictions, but one that has no consensus on an operational definition. How relapse is measured could make substantial differences in clinical practice and in conclusions drawn from empirical studies. The aim of this study was to compare and contrast four different operational definitions of alcohol relapse in a clinical sample of adolescents. The participants were 75 males and females ages 14-18 who presented for outpatient treatment of alcohol use disorder (AUD). They completed an extensive in-person initial assessment, as well as 12 subsequent monthly telephone interviews that concerned their daily alcohol and other drug use and related events. The four alcohol relapse definitions evaluated included: at least 1 day of drinking any amount after at least 4 consecutive days of abstinence; at least 1 heavy (five standard drinks for boys, four for girls) drinking day after 4 abstinent days; at least 1 day of drinking any amount with associated problems after 4 abstinent days; and at least 1 heavy drinking day with associated problems following 4 abstinent days. Relapse events were identified during the first 6 months following the initial interview. The results showed that the time period until relapse varied across the four definitions of relapse ranging from 26 to 90 days. Additional analyses investigated the utility of each of the definitions in predicting functioning during months 7-12 using multiple regression. The results of these analyses showed that the two "heavy drinking" definitions contributed significantly independent variance to predicting average number of drinking days/month and drinks/drinking day and that the two "any drinking" definitions significantly predicted the presence of a current AUD diagnosis. The results suggest that relapse definitions make a difference in estimates of rates and times to first relapse. Furthermore, the occurrence of at least one relapse is predictive of later functioning in a clinical sample of adolescents, which is of practical and theoretical importance. Suggestions for the extensions of this investigation in future research are provided.

This prospective study involved 59 adolescents with drug and alcohol disorders who had just completed outpatient treatment. They participated in a comprehensive baseline assessment, and then participated in monthly telephone assessments of substance use and reasons for use. Despite their recent treatment, two-thirds (66%) of the participants in this study had relapsed to drug use within 6 months. The median time to drug relapse was only 54 days (+/-14 days), or slightly less than 2 months. The three most commonly given reasons for relapse were social pressure, withdrawal, and negative affect. These findings provide a first confirmation of the results of S.A. Brown [Recovery patterns in adolescent substance abuse. (1993). In J. S. Baer, G. A. Marlatt, & R. J. McMahon (Eds.), Addictive behaviors across the life span (pp. 160-183). London: SAGE.] in showing that most adolescents relapse quickly following treatment for substance use disorders.

Change to nonproblem drinking was studied in 159 adolescents (70% male) presenting for alcohol use disorders (AUDs) treatment. A community sample (n = 148,47% male) also was assessed. Clinical participants had a current AUD at baseline; 1 year later, 17% remained abstinent, 60% had at least 1 AUD symptom (problem drinkers), and 23% were drinking but had no AUD symptoms (nonproblem drinkers). Drinking among the nonproblem drinkers decreased and was lower than in the problem drinkers. Nonproblem drinkers increased in psychosocial functioning and decreased in the number of illicit drugs used relative to problem drinkers and generally did not differ from the abstainers. The results suggest alternative views of treatment goals, relapse, and treatment outcome in adolescents.

Recently, a first placebo-controlled study of an selective serotonin reuptake inhibitor (SSRI) medication was conducted among a sample of adolescents with major depression by Emslie et al. [Arch. Gen. Psychiatry 54 (1997) 1031.]. That study demonstrated efficacy for fluoxetine vs. placebo for treating adolescents with major depression. However, to date, no studies have been conducted to assess the efficacy of fluoxetine or any other SSRI medication in adolescents with major depression in combination with an alcohol use disorder (AUD). In this study, the authors investigated whether fluoxetine decreases the depressive symptoms and the drinking of adolescents with comorbid major depression and an AUD. The authors conducted a 12-week open-label study of fluoxetine (20 mg) in 13 adolescents with current comorbid major depression and an AUD. A significant within-group decrease (improvement) was found for both depressive symptoms and drinking during the course of the study. The fluoxetine was well tolerated during the study. These data suggest promise for fluoxetine for decreasing both the depressive symptoms and the drinking of adolescents with comorbid major depression and an AUD.

Clinical course was studied in 131 male and female adolescents with current alcohol use disorder (AUD) at baseline (BL). Participants were classified into 4 groups according to their diagnosis and drinking pattern 1 year later. The 4 groups were compared with each other and with 37 community control participants. Results showed that over half of the clinical sample no longer had a current AUD at 1 year; about 64% were and 36% were not still drinking. BL discriminators of 1-year status were alcohol dependence, other drug use, and coping. All of the clinical groups tended to show improvement at 1 year in the main dependent variables, and the abstainers' level of drug use and coping were comparable with that of the community participants. These findings suggest that many adolescents improve in functioning during the 1 year after alcohol and drug treatment and that a stress and coping model is useful for studying clinical course of AUDs in adolescents.