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

Abstract

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 μg/kg/day for GHD and 53.2 μg/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 (R² = 0.32, p < 0.001) and decrease in fat mass (R² = 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.

Three-Year Efficacy and Safety of LB03002, a Once-Weekly Sustained-Release Growth Hormone (GH) Preparation, in Prepubertal Children with GH Deficiency (GHD)

“…A transient increase from baseline in mean fasting glucose was noted with the 0.7 mg/kg/wk dose of LB03002 and in mean HbA1c with the 0.5 mg/kg/wk dose although not with the higher dose of 0.7 mg/kg/wk. Although there have been concerns of a potential effect of GH administration on glucose homeostasis (22), there is little evidence for a negative effect in GH-treated children unless other risk factors are present (23,24). The current study did not indicate an increased risk of impaired glucose metabolism with LB03002 administration over 36 months.…”

Height, Muscle, Fat and Bone Response to Growth Hormone in Short Children with Very Low Birth Weight Born Appropriate for Gestational Age and Small for Gestational Age

“…In our patients we saw a clear increase of insulin levels within the normal range (table 3). Martin et al [26] have shown that in the short term increase in muscle mass and decrease in fat mass was inversely related to increase in insulin resistance in short children born SGA undergoing GH treatment. None of the known side effects of GH were observed in the children of this study.…”

“…This phenomenon would perhaps deserve further study in a meta-analysis of a large number of GH studies. From our previous studies we would expect slightly lower height velocities of about 5.5 ± 1 cm/year (-0.55 ± 1 SDS) at GH start in short children born SGA [26]. …”

What is the evidence for beneficial effects of growth hormone treatment beyond height in short children born small for gestational age? A review of published literature

“…Findings on the effects of GH therapy on body composition in included studies are summarized in Table 2. Treatment with GH is associated with a substantial reduction in adipose tissue mass and an increase in lean body mass (LBM) [109][110][111][112][113][114]. This leads to a normalization of BMI [109].…”