Metabolic Impact of Growth Hormone Treatment in Short Children Born Small for Gestational Age

Abstract

Background: Growth hormone (GH) treatment in short children born small for gestational age (SGA) may result in metabolic changes with potential long-term effects. Methods: 149 short SGA children (mean birth weight 2.0 ± 0.6 kg, age 5.5 ± 1.5 years, height standard deviation score (SDS) –3.1 ± 0.6) were randomised to: low-dose GH therapy (0.033 mg/kg/day) for 2 years; high-dose GH therapy (0.100 mg/kg/day) for 1 year, or mid-dose GH therapy (0.067 mg/kg/day) for 1 year. Leptin, ghrelin, insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1), lipids, fasting blood glucose and fasting insulin were assessed at baseline, 12 and 24 months. Results: After 1 year of active treatment, GH significantly reduced serum ghrelin and increased IGF-I SDS and insulin levels. Regression analysis showed an inverse correlation between ghrelin and IGF-I SDS (p < 0.001). Leptin and IGFBP-1 also declined (both p < 0.05). Changes in insulin levels reversed upon discontinuation. Improvements in lipid profile were nonsignificant and fasting blood glucose levels remained within the normal range. Conclusion: In short SGA children, ghrelin and leptin reductions associated with GH treatment may occur through a negative feedback loop of the GH–IGF-I axis. Consequently, via ghrelin and leptin suppression, GH treatment may modify food intake and body composition and potentially improve long-term metabolic outcomes.

Ghrelin, insulin-like growth factor I and adipocytokines concentrations in born small for gestational age prepubertal children after the catch-up growth

“…First, it was proved that in ISS AGA children, the ghrelin concentration is higher while IGF-I is lower than in controls [31,32]. In turn, in SGA children without catch-up growth who remain short, GH treatment improves final height [33] and brings about favourable long-term metabolic benefits [34]. Thus, it appeared interesting for us to compare the analysed parameters among these groups.…”

Insulin Sensitivity Modulates the Growth Response during the First Year of High-Dose Growth Hormone Treatment in Short Prepubertal Children Born Small for Gestational Age

“…In this study, we evaluated in particular whether the amplitude of the growth response to GH was associated with pretreatment values or changes in fasting insulin, IGF-1 and leptin, which have been shown to change significantly during GH therapy and have a possible impact on body growth [9,13,20,21,22]. Data on the fasting leptin concentration at the start of GH therapy in relation to the first-year growth response to GH are conflicting, which might be explained either by differences in GH dosing or the pretreatment nutritional status of the subjects between studies [10,13,22]. Serum leptin concentration measured at the start was unrelated to the growth response in our subjects, who presented with a rather low BMI SDS.…”

The influence of a long-term growth hormone treatment on lipid and glucose metabolism: a randomized trial in short Japanese children born small for gestational age

“…Increases in insulin resistance may cause impairments in the growth hormone (GH)-insulin-like growth factor (IGF)-binding protein axis or be a consequence of these impairments [9]. …”