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

Area of Science:

• Pediatric Endocrinology
• Growth Hormone Axis Research
• Metabolic Disorders in Children

Background:

• Childhood obesity is associated with enhanced growth and altered growth hormone-insulin-like growth factor (GH-IGF) axis.
• The roles of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) in IGF bioavailability within pediatric obesity remain uninvestigated.

Purpose of the Study:

• To investigate the impact of childhood obesity and subsequent weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2.
• To examine the relationship between these factors and IGF bioavailability, growth parameters, and other GH-IGF system components.

Main Methods:

• Studied prepubertal children with severe obesity (n=150) at diagnosis and after weight loss.
• Compared obese children to 206 age- and sex-matched healthy controls.
• Measured serum concentrations of PAPP-A, PAPP-A2, STC1, STC2, IGF-I, IGF-II, IGF binding proteins, and insulin.

Main Results:

• Obese children exhibited lower PAPP-A, PAPP-A2, and STC2, but higher total/free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin.
• No correlation was found between BMI or height z-scores and the measured biochemical parameters.
• Weight loss led to decreased IGF-II, insulin, and ALS, with increased IGFBP-2, IGFBP-5, STC2, and PAPP-A.

Conclusions:

• Elevated circulating IGF-I, IGF-II, and insulin in obese children likely contribute to accelerated growth and bone maturation.
• STC2 may play a role in the altered growth observed in prepubertal obesity.