ESPE Abstracts (2019) 92 P2-162

Metabolic Effects of Growth Hormone Treatment in Short Prepubertal Children: A Double-Blinded Randomized Clinical Trial

Anders Tidblad1, Jan Gustafsson2, Claude Marcus3, Martin Ritzén1, Klas Ekström1

1Division of Pediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 2Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden. 3Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden

Objective: Growth hormone (GH) is a central hormone for regulating linear growth during childhood and also highly involved in metabolism of lipids, carbohydrates and protein. However, few studies report on how treatment with GH during childhood influences metabolic parameters. Our aim was to investigate metabolic effects of different doses of GH in short children with GH peak levels in the low normal range.

Design: Thirty-five pre-pubertal short children (<-2.5 SDS), aged 7-10 years, with peak levels of GH between 7 and 14 µg/L during an arginine insulin tolerance test (AITT), were randomized to three different doses (10/30/100 µg/kg/d) of GH treatment for 2 years. The doses were blinded for both patients and study investigators. Auxological and metabolic investigations were performed. These included metabolites in blood and interstitial microdialysis fluid, dual-energy X-ray absorptiometry (DEXA), frequently sampled intravenous glucose tolerance test (FSIVGTT) and stable isotope examinations of rates of glucose production and lipolysis.

Results: At 24 months, the high dose group (HD) had higher fasting insulin compared with the standard dose (SD) and low dose (LD) groups (HD: 111.7 vs SD: 61.2 and LD: 46.0 pmol/L [p=<0.001]) and showed signs of insulin resistance (HOMA-IR, HD: 4.20 vs SD: 2.17 and LD: 1.71 (LD) [p=<0.001]). The FSIVGTT also demonstrated higher acute insulin response (AIR, HD: 667 vs SD: 418 and LD: 348 mU×L-1×min [p=<0.05]). Few other metabolic differences were found at 24 months but a decreased insulin sensitivity index (Si) could already be seen at 12 months for both SD and HD compared with the LD group (Si, HD: 5.4, SD: 6.4 vs LD: 10.1 [mU/l]-1×min-1 [p=<0.05]).

Conclusion: Treatment with GH has a dose-dependent effect on insulin sensitivity in short prepubertal children leading to higher levels of fasting insulin and signs of insulin resistance in both HOMA indices and FSIVGTT examinations.

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