BMI and Contraceptives Affect New Age-, Sex-, and Puberty-adjusted IGF-I and IGFBP-3 Reference Ranges Across Life Span

Abstract

Context: Various clinical factors influencing serum levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are not entirely consistently described. Objective: We asked whether body mass index (BMI), contraceptive drugs (CDs), and hormone replacement therapy (HRT) have potential effects on data for interpreting new age-, sex-, and puberty-adjusted reference ranges for IGF-I and IGFBP-3 serum levels. Design and Setting: Subjects were mainly participants from 2 population-based cohort studies: the LIFE Child study of children and adolescents and the LIFE Adult study. Participants: We investigated 9400 serum samples from more than 7000 healthy and 1278 obese subjects between 3 months and 81 years old. Main Outcome Measures: Associations between IGF-I or IGFBP-3, measured with a new electrochemiluminescence immunoassay, and the predictors BMI and CDs were estimated using hierarchical linear modeling. Results: During infancy, obese children had up to 1 SD score (SDS) higher mean predicted IGF-I values, converging with levels of normal-weight subjects up to 13 years old. Between 20 and 40 years of age, obesity was related to up to -0.5 lower IGF-I SDS values than the predicted values. Obesity had less impact on IGFBP-3. Estrogen- and progestin-based CDs, but not HRT, decreased IGF-I and increased IGFBP-3 (P < 0.01) in adolescents (β IGF-I = -0.45, β IGFBP-3  = 0.94) and adults (β IGF-I = -0.43, β IGFBP-3  = 1.12). Conversely, progestin-based CDs were significantly positive associated with IGF-I (β IGF-I  =0.82). Conclusions: BMI and CDs must be considered when assessing and interpreting the clinical relevance of IGF-I and IGFBP-3 measurements.