Longitudinal analysis of the insulin-like growth factor system in African-American and European American children and adolescents

Abstract

Context: IGF-I and its binding proteins influence growth, development, and disease risk. Studies have revealed ethnic variations in the IGF system.

Objective: This longitudinal study was undertaken to test the hypothesis that the ethnic differences in the IGF system exist throughout the pubertal transition, and these differences are mediated at least in part by inherent differences in insulin dynamics.

Design: This was a longitudinal study. Annual evaluations were conducted for pubertal maturation, body composition, acute insulin response to glucose (AIRg), and reproductive-endocrine profile. Hormones and binding proteins were determined using standard assays, the AIRg during a frequently sampled iv glucose tolerance test, and body composition by dual-energy x-ray absorptiometry. Mixed model analyses were used to identify and characterize ethnic differences in the IGF system across the pubertal transition after adjusting for ethnicity, sex, age, maturation status, body composition, and reproductive hormones, and to identify the contribution of insulin to IGF binding protein (IGFBP)-1.

Participants: Subjects included African-American (AA) and European American children (n = 162 at baseline) aged 7-16 yr, evaluated across the pubertal transition.

Main outcome measures: Annual data on IGF-I, IGFBP-1, and IGFBP-3 were examined.

Results: IGF-I was higher in AA children at pubertal stage 1 only (P < 0.001). However, IGFBP-3 and IGFBP-1 concentrations were lower in AAs through much of puberty (P < 0.05). The lower IGFBP-1 of AAs was in part explained by greater AIRg.

Conclusions: Our data suggest that the higher IGF-I and lower IGFBP-1 and IGFBP-3 levels in AAs as compared with European Americans during puberty suggest potential ethnic differences in circulating bioavailable IGF-I. In addition, higher AIRg in AAs may lead to greater bioavailable IGF-I. Whether these differences in the IGF system account for disparities in disease risk warrants further investigation.

Figure 1

A, Least squares mean (± se) for total IGF-I by ethnicity at each pubertal stage. Means are adjusted for sex, age, reproductive hormones, and body fat mass. Shaded bars represent EA, and dark bars represent AA children. *, AAs had significantly higher IGF-I only at TS I (P < 0.0001). To convert metric units (ng/ml) to International System of Units (nmol/liter) for IGF-I, multiply by 0.131. B, Least squares mean (± se) for IGFBP-3 by ethnicity at each TS. Means are adjusted for sex, age, reproductive hormones, and body fat mass. Shaded bars represent EA, and dark bars represent AA children. *, AAs had significantly lower IGFBP-3 at all TSs (P < 0.05). To convert metric units (ng/ml) to International System of Units (nmol/liter) for IGFBP-3, multiply by 0.035. C, Least squares mean (± se) for IGFBP-1 by ethnicity at each TS. Means are adjusted for sex, age, reproductive hormones, and body fat mass. Shaded bars represent EA, and dark bars represent AA children. *, AAs had significantly lower IGFBP-1 at TSs I–III and V (P < 0.05). D, Least squares mean (± se) for IGFBP-1 by ethnicity at each TS. Means are adjusted for sex, age, reproductive hormones, and body fat mass, and the AIRg, an approximation of first-phase insulin secretion. Shaded bars represent EA, and dark bars represent AA children. *, AAs had significantly lower IGFBP-1 at TSs I–III. Therefore, inclusion of AIRg in the model explained the ethnic differences in IGFBP-1 in childhood and early puberty. Sample size at each TS: for AAs, I (n = 59), II (n = 43), III (n = 35), and IV/V (n = 45); and for EAs, I (n = 71), II (n = 63), III (n = 42), and IV/V (n = 37).