Prepubertal children with obesity have high free IGF-1 levels and accelerated growth despite reduced pappalysin levels.

Abstract

Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation and changes in the GH-IGF axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity. We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1 and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system. Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls. Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I (fIGF-I), intact IGFBP-3, ALS, IGF-II and insulin levels, with no difference in the free/total IGF-I ratio. Neither the standardized BMI nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2 and PAPP-A were observed after weight loss. Increased circulating total and free IGF-I, insulin and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.