Background: Pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment with GH 1 mg/m2 per day (~0.033 mg/kg per day) in combination with 2 years of GnRH analogue (2 years GnRHa) and even more so with 2 mg/m2 per day (~0.067 mg/kg per day). Concerns haven been raised about the effects of GH and GnRHa on insulin sensitivity on the long-term.
Objective and hypotheses: To investigate insulin sensitivity and β-cell function during long-term GH treatment, either with or without 2 years of GnRHa. To study whether GH 2 mg/m2 per day results in a less favorable insulin sensitivity at AH than GH 1 mg/m2 per day.
Method: Longitudinal, randomised, dose-response GH trial involving 110 short SGA children (59 girls) treated with GH until AH; 67 received also 2 years GnRHa. Frequently sampled intravenous glucose tolerance (FSIGT) tests were performed and insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response (AIR) and disposition index (DI) were calculated using Bergmans MINMOD MILLENIUM software. The GH-dose effect was evaluated in a subgroup of 48 children who started GH treatment in early puberty (random 1 or 2 mg/m2 per day) with 2 years of GnRHa.
Results: At AH, Si, Sg and AIR were similar between children treated with GH/2 year GnRHa and those treated with only GH. In the pubertal subgroup there was no GH dose-effect on Si, Sg, AIR and DI. In addition, we performed an FSIGT in 15 children at start and after 3 months of only GnRHa. There was no significant change in Si, Sg, AIR and DI during only GnRHa treatment.
Conclusion: Combined GH/2 years GnRHa has no long-term negative effects on insulin sensitivity and β-cell function compared to only GH. Started in early puberty, a GH-dose of 2 mg/m2 per day results in a similar insulin sensitivity at AH as a dose of 1 mg GH/m2 per day.
Funding: This study was an investigator initiated study, supported by an independent research grant from Pfizer B.V. The Netherlands.
01 Oct 2015 - 03 Oct 2015