Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels.

Abstract

Background: Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone-insulin-like growth factor (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.

Objective: 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.

Methods: 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.

Results: Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (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.

Conclusion: 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.