Publications by authors named "Norman K Pollock"

36 Publications

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

Int J Obes (Lond) 2020 05 21;44(5):1152-1163. Epub 2019 Nov 21.

Pediatrics, MCG, Augusta University, Augusta, GA, USA.

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 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.
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http://dx.doi.org/10.1038/s41366-019-0482-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192762PMC
May 2020

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

Pediatr Obes 2019 11 11;14(11):e12560. Epub 2019 Jul 11.

Department of Pediatrics, Children's Hospital Los Angeles, The University of Southern California, Los Angeles, CA, USA.

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.
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http://dx.doi.org/10.1111/ijpo.12560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812591PMC
November 2019

Proportionality at birth and left ventricular hypertrophy in healthy adolescents.

Early Hum Dev 2019 05 3;132:24-29. Epub 2019 Apr 3.

Department of Pediatrics, Medical College of Georgia, Augusta University, Augusta, GA, USA; Vascular Biology Center, Augusta University, Augusta, GA, USA. Electronic address:

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 and Ponderal index (PI); weight/length) 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 = 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.
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http://dx.doi.org/10.1016/j.earlhumdev.2019.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101490PMC
May 2019

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

J Bone Miner Res 2018 11 27;33(11):1940-1947. Epub 2018 Aug 27.

Department of Foods and Nutrition, University of Georgia, Athens, GA, USA.

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 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 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) 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) 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.
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http://dx.doi.org/10.1002/jbmr.3550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556206PMC
November 2018

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

Am J Hypertens 2018 05;31(6):735-741

Georgia Prevention Institute, Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.

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.
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http://dx.doi.org/10.1093/ajh/hpy049DOI Listing
May 2018

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

PLoS One 2017 7;12(12):e0188424. Epub 2017 Dec 7.

Georgia Prevention Institute, Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, Georgia, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188424PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720756PMC
December 2017

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

Public Health Rep 2017 Nov/Dec;132(2_suppl):65S-73S

5 Georgia Prevention Institute, Augusta University, Augusta, GA, USA.

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.
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http://dx.doi.org/10.1177/0033354917731308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5692181PMC
December 2017

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

J Nutr 2017 Oct;147(10):1960-1967

Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, GA.

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.
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http://dx.doi.org/10.3945/jn.117.253666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610549PMC
October 2017

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

Calcif Tissue Int 2017 11 14;101(5):479-488. Epub 2017 Jul 14.

Department of Foods and Nutrition, The University of Georgia, 279 Dawson Hall, 305 Sanford Drive, Athens, GA, USA.

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.
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http://dx.doi.org/10.1007/s00223-017-0303-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705220PMC
November 2017

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

J Nutr 2017 07 7;147(7):1296-1300. Epub 2017 Jun 7.

Departments of Foods and Nutrition and

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. 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. Healthy black and white girls aged 9-11 y were randomly assigned to daily supplementation of zinc (9 mg elemental Zn/d; = 75; blacks: = 35) or placebo ( = 72; blacks: = 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. Baseline plasma zinc was not correlated with C-peptide ( = -0.07), insulin ( = -0.06), or HOMA2-IR ( = -0.09) (all > 0.05) after controlling for race and age. Treatment × time interactions for C-peptide and HOMA2-IR were not significant (both > 0.05). Although the treatment × race × time interactions for C-peptide and HOMA2-IR were not significant (both = 0.08), black girls who received the placebo experienced slight increases in C-peptide (15.7%) and HOMA2-IR (17.7%) ( = 0.06). 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.
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http://dx.doi.org/10.3945/jn.117.248013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483963PMC
July 2017

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

Endocrinology 2017 05;158(5):1160-1171

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912.

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.
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http://dx.doi.org/10.1210/en.2016-1250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460837PMC
May 2017

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

J Bone Miner Res 2017 Jul;32(7):1537-1545

Department of Foods and Nutrition, The University of Georgia, Athens, GA, USA.

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  < 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 = 0.321, p < 0.001). However, this relationship was moderated in the children with high (β = 0.200, p < 0.001) versus normal (β = 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.
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http://dx.doi.org/10.1002/jbmr.3132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489353PMC
July 2017

Nonlinear Relationship between Birth Weight and Visceral Fat in Adolescents.

J Pediatr 2016 Jul 9;174:185-92. Epub 2016 May 9.

Georgia Prevention Institute, Augusta University, Augusta, GA; Department of Pediatrics, Medical College of Georgia, Augusta University, Augusta, GA.

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.
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http://dx.doi.org/10.1016/j.jpeds.2016.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711485PMC
July 2016

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

PLoS One 2016 6;11(4):e0152849. Epub 2016 Apr 6.

Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152849PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822838PMC
August 2016

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

J Nutr 2015 Dec 21;145(12):2699-704. Epub 2015 Oct 21.

Department of Foods and Nutrition, The University of Georgia, Athens, GA; Departments of

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.
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http://dx.doi.org/10.3945/jn.115.218792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656906PMC
December 2015

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.

BMC Obes 2015 4;2:27. Epub 2015 Jul 4.

Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Building HS-1640, Augusta, 30912-3715 GA USA.

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.
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http://dx.doi.org/10.1186/s40608-015-0056-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511449PMC
July 2015

Childhood obesity, bone development, and cardiometabolic risk factors.

Authors:
Norman K Pollock

Mol Cell Endocrinol 2015 Jul 27;410:52-63. Epub 2015 Mar 27.

Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.mce.2015.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444415PMC
July 2015

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

Int J Sport Nutr Exerc Metab 2015 Apr 14;25(2):136-44. Epub 2014 Jul 14.

Dept. of Foods and Nutrition, University of Georgia, Athens, GA.

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.
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http://dx.doi.org/10.1123/ijsnem.2013-0258DOI Listing
April 2015

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

J Neurosci 2014 Feb;34(7):2618-31

Department of Physiology and Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.

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.
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http://dx.doi.org/10.1523/JNEUROSCI.4200-13.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921429PMC
February 2014

Dietary sodium, adiposity, and inflammation in healthy adolescents.

Pediatrics 2014 Mar 2;133(3):e635-42. Epub 2014 Feb 2.

Georgia Prevention Center, Institute of Public and Preventive Health, and.

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.
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http://dx.doi.org/10.1542/peds.2013-1794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934330PMC
March 2014

Weight gain in college females is not prevented by isoflavone-rich soy protein: a randomized controlled trial.

Nutr Res 2014 Jan 22;34(1):66-73. Epub 2013 Oct 22.

Department of Foods and Nutrition, The University of Georgia, Athens, GA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.nutres.2013.09.005DOI Listing
January 2014

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

Pediatr Res 2013 Aug 22;74(2):206-10. Epub 2013 May 22.

Department of Pediatrics, Georgia Prevention Institute, Georgia Regents University, Augusta, Georgia, USA.

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.
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http://dx.doi.org/10.1038/pr.2013.81DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332551PMC
August 2013

Associations of total and undercarboxylated osteocalcin with peripheral and hepatic insulin sensitivity and β-cell function in overweight adults.

J Clin Endocrinol Metab 2013 Jul 24;98(7):E1173-80. Epub 2013 Apr 24.

Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama 35294-3360, USA.

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.
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http://dx.doi.org/10.1210/jc.2013-1203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701277PMC
July 2013

Adenovirus 36, adiposity, and bone strength in late-adolescent females.

J Bone Miner Res 2013 Mar;28(3):489-96

Department of Foods and Nutrition, The University of Georgia, Athens, GA, USA.

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.
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http://dx.doi.org/10.1002/jbmr.1776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705225PMC
March 2013

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

JAMA 2012 Sep;308(11):1103-12

Georgia Prevention Center, Institute for Public and Preventive Health, Department of Pediatrics, Medical College of Georgia, 1120 15th St, Ste 1640, Augusta, GA 30912, USA.

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.
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http://dx.doi.org/10.1001/2012.jama.10762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487697PMC
September 2012

Adolescent fiber consumption is associated with visceral fat and inflammatory markers.

J Clin Endocrinol Metab 2012 Aug 16;97(8):E1451-7. Epub 2012 May 16.

Department of Pediatrics, Georgia Health Sciences University, Augusta, Georgia 30912, USA.

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.
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http://dx.doi.org/10.1210/jc.2012-1784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410273PMC
August 2012

Circulating 25-hydroxyvitamin D concentrations are correlated with cardiometabolic risk among American black and white adolescents living in a year-round sunny climate.

Diabetes Care 2012 May 12;35(5):1133-8. Epub 2012 Mar 12.

Corresponding author: Yanbin Dong,

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.
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http://dx.doi.org/10.2337/dc11-1944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329810PMC
May 2012

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

J Nutr 2012 Feb 21;142(2):251-7. Epub 2011 Dec 21.

Department of Pediatrics, Georgia Health Sciences University, Augusta, GA, USA.

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.
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http://dx.doi.org/10.3945/jn.111.150219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260058PMC
February 2012