Growth hormone-induced increases in skeletal muscle mass alleviates the associated insulin resistance in short children born small for gestational age, but not with growth hormone deficiency.

Purpose: To assess the effect of growth hormone (GH) treatment on body composition and insulin resistance, and the interdependence of these factors, in short children born small for gestational age (SGA) and children with growth hormone deficiency (GHD).

Methods: In this longitudinal study we describe the relationship between changes in fasting hormone levels, and forearm cross-sectional fat/muscle area in 54 short children with GHD and 37 short children born SGA during the first 12 months of GH treatment. Mean GH dose was 31.4 microg/kg/day for GHD and 53.2 microg/kg/day for SGA. HOMA2-IR was calculated as a steady-state fasting measure of insulin resistance.

Results: At baseline the SGA group displayed higher fasting glucose, insulin, C-peptide serum levels and higher HOMA2-IR (p < 0.01) than GHD patients despite similar low muscle mass and less fat mass. Both groups had low muscle mass for height, and mean changes in muscle, fat, insulin, C-peptide and HOMA2-IR during GH treatment were also similar. HOMA2-IR correlated positively with IGF-1 changes in both groups. In the SGA group, but not in the GHD group, the increase in fasting serum insulin, C-peptide and HOMA2-IR correlated negatively with increase in muscle mass (R(2) = 0.32, p < 0.001) and decrease in fat mass (R(2) = 0.12, p = 0.034).

Conclusions: In SGA, unlike in GHD, the insulin resistance caused by GH treatment appears to be diminished by the GH-induced increase in muscle mass and decrease in fat mass.