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.

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.

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.

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.

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.

Obesity elicits interleukin 1-mediated deficits in hippocampal synaptic plasticity.

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 1ß (IL1ß) 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.

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.

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.

Urinary prostasin excretion is associated with adiposity in nonhypertensive African-American adolescents.

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.

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.

Greater fructose consumption is associated with cardiometabolic risk markers and visceral adiposity in adolescents.

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 (ß = 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.

Exercise dose and diabetes risk in overweight and obese children: a randomized controlled trial.

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.

Adolescent obesity, bone mass, and cardiometabolic risk factors.

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 (ß = -0.22), waist circumference (ß = -0.23), homeostasis model assessment of insulin resistance (ß = -0.23), and high-density lipoprotein cholesterol level (ß = 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.

Comparisons of trabecular and cortical bone in late adolescent black and white females.

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.

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.

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.

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.

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.

Is adiposity advantageous for bone strength? A peripheral quantitative computed tomography study in late adolescent females.

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.