Cardiometabolic Risk and Its Relationship With Visceral Adiposity in Children With Cerebral Palsy.

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.

Exercise effects on arterial stiffness and heart health in children with excess weight: The SMART RCT.

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 (VÈ®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.

Maternal blood pressure mediates the association between maternal obesity and infant weight gain in early postpartum.

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 (ß = .29) and BP (ß = .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.

Proportionality at birth and left ventricular hypertrophy in healthy adolescents.

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/length2 and Ponderal index (PI); weight/length3) 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 (Pquadratic = 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.

Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents.

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 D3 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 D3 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.

Inactive Matrix Gla Protein, Arterial Stiffness, and Endothelial Function in African American Hemodialysis Patients.

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 ß = 0.49) and FMD (standardized ß = -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.

Dose responses of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency: A placebo controlled randomized trial.

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.

Fitness, Sleep-Disordered Breathing, Symptoms of Depression, and Cognition in Inactive Overweight Children: Mediation Models.

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.

Phylloquinone Intake Is Associated with Cardiac Structure and Function in Adolescents.

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.

Obese Versus Normal-Weight Late-Adolescent Females have Inferior Trabecular Bone Microarchitecture: A Pilot Case-Control Study.

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.

Zinc Supplementation Does Not Alter Indicators of Insulin Secretion and Sensitivity in Black and White Female Adolescents.

Background: Zinc is a micronutrient involved in the production of, and peripheral sensitivity to, pancreatic ß 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.

Whole-Body Vibration Mimics the Metabolic Effects of Exercise in Male Leptin Receptor-Deficient Mice.

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.

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.

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 (pInteraction < 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 (ßIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (ßIndirect Effect = 0.200, p < 0.001) versus normal (ßIndirect 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.

Correction: Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings.

[This corrects the article DOI: 10.1371/journal.pone.0152849.].

Nonlinear Relationship between Birth Weight and Visceral Fat in Adolescents.

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.

Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings.

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 (ß = 0.20, p<0.01), but not in Caucasians (ß = 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.

Zinc Supplementation Increases Procollagen Type 1 Amino-Terminal Propeptide in Premenarcheal Girls: A Randomized Controlled Trial.

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.

Dose and time responses of vitamin D biomarkers to monthly vitamin D3 supplementation in overweight/obese African Americans with suboptimal vitamin d status: a placebo controlled randomized clinical trial.

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.

Childhood obesity, bone development, and cardiometabolic risk factors.

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.

Load-specific physical activity scores are related to tibia bone architecture.

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.