Growth hormone treatment does not to lead to insulin resistance nor excessive rise in IGF-1 levels, while improving height in patients small for gestational age A long-term observational study

Abstract

Objective: In children born small for gestational age (SGA), the relationship between growth hormone (GH) treatment and insulin resistance (IR) has only been investigated for a short period, necessitating a longer observation period. This study aimed to evaluate the long-term (10 years) effect of GH to SGA-children on IR and safety during treatment.

Design: This was a multicenter observational study.

Patients: SGA-children who received GH treatment in Spain (stratified by Tanner-stage and age at GH onset [two groups: ≤6 years old or >6 years old]).

Measurements: The analysed variables (yearly measures) included auxologic, metabolic (insulin-like growth factor-1 (IGF-1), height velocity [HV], weight and homeostatic model assessment-IR [HOMA-IR]) and safety data. Data were collected prospectively (since the study approval: 2007) and retrospectively (since the initiation of GH treatment: 2005-2007).

Results: A total of 389 SGA children (369 Tanner-I) were recruited from 27 centres. The mean age (standard deviation) of the children at GH treatment onset was 7.2 (2.8) years old. IGF-1 (standard deviation score [SDS]) and HOMA-IR values tended to increase until the sixth year of GH-treatment, with significant differences being observed only during the first year, while these remained stable in the later years (within normal ranges). Height (SDS) increased significantly (basal: -3.0; tenth year: -1.13), and the maximum HV (SDS) occurred during the first year (2.75 ± 2.39).

Conclusions: HOMA-IR values increased significantly in SGA-children during the first year of GH-treatment, remained stable and were within normal ranges in all cases. Our 10-year data suggests that long-term GH treatment does not promote IR and is well-tolerated, safe and effective.

Keywords: efficacy; growth hormone; homeostatic model assessment; insulin resistance; long-term follow-up; safety; small for gestational age.