Birth weight is associated with the IGF-1 response to GH in children: Programming of the anabolic action of GH?

Abstract

Context: Intrauterine programming of the somatotropic axis has been hypothesized in cases of intrauterine growth retardation. Objective: The objective of the study was to study the effects of birth weight and body composition on GH sensitivity. Design: This was a cross-sectional study with a single GH administration to assess GH sensitivity. Setting: The study was conducted at the Department of Pediatric Endocrinology of an academic medical center. Patients: One hundred normal short children aged from 4 to 17 years old (44 girls, 56 boys) separated into four groups: early childhood (aged 4-8 y, n = 14), late childhood (aged 9-12 y, pubertal stage 1, n = 30), early puberty (aged 10-15 y, stage 2, n = 32), and midpuberty (aged 12-17 y, stages 3 and 4, n = 24). Intervention and Main Outcome Measure: Serum IGF-1 at baseline and 24 hours after a single administration of GH (2 mg/m2) were measured. Results: δIGF-1 significantly increased across the groups (P < .0001) with no gender difference, whereas the percentage of change in IGF-1 was similar (47% ± 32%). Independent predictors of δIGF-1 were birth weight SD score, fat percentage, fasting insulin (all positive predictors), and free fatty acids (negative predictor), with age, puberty, and baseline IGF-1 as adjusting variables (multiple R = 0.73, P < .0001). Independent predictors of the percentage of change in IGF-1 were birth weight SD score, fat percentage, and baseline IGF-1 (multiple R = 0.43, P < .001). Conclusion: This study suggests that in cases of low birth weight, intrauterine programming of GH sensitivity may be an adaptation to an expected poor postnatal nutritional environment, serving to restrict the anabolic action of GH. Conversely, postnatal excess energy stores may promote the anabolic action of GH.