Browsing by Author "Lewis, Richard D."

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    Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States
    (BioMed Central, 2017-03-07) Virecoulon Giudici, Kelly; Kindler, Joseph M.; Martin, Berdine R.; Laing, Emma M.; McCabe, George P.; McCabe, Linda D.; Hausman, Dorothy B.; Martini, Lígia Araújo; Lewis, Richard D.; Weaver, Connie M.; Peacock, Munro; Hill Gallant, Kathleen M.; Department of Medicine, IU School of Medicine
    BACKGROUND: This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9-13 years. METHODS: This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9-13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. RESULTS: Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-β after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = -0.16; p = 0.04) and glucose (partial r = -0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-β after adjusting for age, sex and percent body fat (all p < 0.001). CONCLUSIONS: These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported.
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    Bone Turnover is not Influenced by Serum 25-Hydroxyvitamin D in Pubertal Healthy Black and White Children
    (Elsevier B.V., 2012-10) Hill, Kathleen M.; Laing, Emma M.; Hausman, Dorothy B.; Acton, Anthony; Martin, Berdine R.; McCabe, George P.; Weaver, Connie M.; Lewis, Richard D.; Peacock, Munro; Department of Medicine, IU School of Medicine
    Low serum 25-hydroxyvitamin D [25(OH)D] is common in healthy children particularly in blacks. However, serum 25(OH)D concentrations for optimal bone turnover in children is unknown and few data exist that describe effects of increasing serum 25(OH)D on bone turnover markers during puberty. The purpose of this study was to determine the relationships between serum 25(OH)D and changes in serum 25(OH)D and bone turnover in white and black pubertal adolescents. Bone turnover markers were measured in 318 healthy boys and girls from Georgia (34°N) and Indiana (40°N) who participated in a study of oral vitamin D3 supplementation (0 to 4000 IU/d). Serum 25(OH)D, osteocalcin, bone alkaline phosphatase, and urine N-telopeptide cross-links were measured at baseline and 12 weeks. Relationships among baseline 25(OH)D and bone biomarkers, and between changes over 12 weeks were determined and tested for effects of race, sex, latitude, and baseline 25(OH)D. Median 25(OH)D was 27.6 ng/mL (n=318, range 10.1–46.0 ng/mL) at baseline and 34.5 ng/mL (n=302, range 9.7–95.1 ng/mL) at 12 weeks. Neither baseline nor change in 25(OH)D over 12 weeks were associated with bone turnover. The lack of association was not affected by race, sex, latitude, or baseline serum 25(OH)D. Serum 25(OH)D in the range of 10-46 ng/mL appears to be sufficient for normal bone turnover in healthy black and white pubertal adolescents.
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    Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9-13 Years
    (Wiley, 2017-07) Kindler, Joseph M.; Pollock, Norman K.; Laing, Emma M.; Oshri, Assaf; Jenkins, Nathan T.; Isales, Carlos M.; Hamrick, Mark W.; Ding, Ke-Hong; Hausman, Dorothy B.; McCabe, George P.; Martin, Berdine R.; Gallant, Kathleen M. Hill; Warden, Stuart J.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.; Department of Medicine
    IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect = 0.200, p < 0.001) versus normal (βIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed.
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    Racial Differences in Cortical Bone Mass, Size and Estimated Strength at the Tibial Diaphysis in Early Pubertal Children
    (Office of the Vice Chancellor for Research, 2012-04-13) Warden, Stuart J.; Ferira, Ashley J.; Laing, Emma M.; Hill, Kathleen M.; Martin, Berdine R.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.
    Osteoporotic fracture rates differ according to race, with blacks having up to half the rate of whites. The reduced fracture rate in blacks has been suggested to be due to their superior bone mass; however, mass is not the sole determinant of bone strength. Bone strength, and consequent fracture risk, is also influenced by how bone material is distributed or structured. It is likely bone structure also contributes to the lower incidence of fractures in blacks and that racial differences in bone structure have roots in childhood. The aim of this study was to assess the influence of race on pQCT-derived cortical bone mass, size and estimated strength at the tibial diaphysis in early pubertal children. 160 children were recruited, with equal subjects according to race (black, n=80; white, n=80) and sex (female, n=80; male, n=80). Subjects were at sexual maturation stages 2 or 3. Tomographic slices of the tibial diaphysis at 66% proximal from the medial malleolus were acquired using pQCT. Slices were assessed for cortical volumetric BMD (Ct.vBMD), cortical BMC (Ct.BMC), total (Tt.Ar) and cortical (Ct.Ar) area, density weighted maximum (IMAX) and minimum (IMIN) second moments of area, density-weighted polar strength-strain index (SSIP), and muscle cross-sectional area (mCSA). Group differences were assessed by two-way analysis of covariance, with race (black vs. white) and sex (female vs. male) as independent variables. Covariates included predicted years from peak height velocity (maturity offset), tibial length and mCSA. There were no interactions between race and sex (all P=0.50-0.98) or main effect for sex (all P=0.08-0.45). Blacks had 15.7% more Ct.BMC, and 10.8-11.8% larger Tt.Ar and Ct.Ar than whites (all P<0.001). The greater enhancement of Ct.BMC relative to Ct.Ar resulted in blacks having 3.6% greater Ct.vBMD than whites (P<0.001). The combination of increased cortical bone mass, size and density in blacks contributed to enhanced estimated bone strength, with IMAX, IMIN and SSIP being 20.0%, 34.5% and 25.2% greater in blacks than whites, respectively (all P<0.001). These data indicate that early pubertal black children have enhanced bone mass, size and estimated bone strength at the tibial diaphysis versus whites, independent of tibial length and mCSA. They suggest bone structural differences may contribute to observed racial differences in fracture rates and that structural divergence between races develops during childhood.
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    Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents
    (Wiley, 2018-11) Wright, Christian S.; Laing, Emma M.; Pollock, Norman K.; Hausman, Dorothy B.; Weaver, Connie M.; Martin, Berdine R.; McCabe, George P.; Peacock, Munro; Warden, Stuart J.; Gallant, Kathleen Hill; Lewis, Richard D.; Medicine, School of Medicine
    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.
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    Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children
    (Endocrine Society, 2016-04) Ferira, Ashley J.; Laing, Emma M.; Hausman, Dorothy B.; Hall, Daniel B.; McCabe, George P.; Martin, Berdine R.; Hill Gallant, Kathleen M.; Warden, Stuart J.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.; Medicine, School of Medicine
    CONTEXT: Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. OBJECTIVE: The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9–13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial. DESIGN: Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model. RESULTS: Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P < .003) over the 12 weeks, despite vitamin D dose-dependent increases in serum 25(OH)D. CONCLUSIONS: Despite significant baseline inverse relationships between serum 25(OH)D and measures of insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.