ESPE Abstracts (2018) 89 RFC4.6

Effect of 2 Years of Growth Hormone Treatment on Glucose Tolerance in Adults with Prader-Willi Syndrome

Layla Damena,b, Stephany Donzea,b, Renske Kuppensa,b, Nienke Bakkera,b & Anita Hokken-Koelegaa,b

aDutch Growth Research Foundation, Rotterdam, Netherlands; bErasmus Medical Center, Rotterdam, Netherlands

Background: In children with Prader-Willi syndrome (PWS), the benefits of growth hormone (GH) treatment are well established. GH has substantially changed the phenotype of children with PWS. Discontinuation of GH after adult height (AH) attainment leads to a decrease in lean body mass and an increase in body fat percentage. Due to their abnormal body composition, adults with PWS are predisposed to develop impaired glucose tolerance (IGT) and diabetes mellitus type 2 (T2DM). Reports on the prevalence of T2DM vary from 7–24% in adults with PWS. Studies in adults with PWS showed positive effects of GH on body composition and metabolic health parameters, but GH is known to induce insulin resistance, which might lead to IGT. In children with PWS, GH has no adverse effects on glucose homeostasis, but data in GH-treated adults are limited.

Aims: To investigate the effect of continuation of GH after AH attainment on glucose homeostasis.

Methods: 40 young adults (mean age 19 years) received at least 2 years of GH after attainment of AH in a standard dose of 0.33 mg/m2 per day (≈0.035 mg/kg per day). Dose was adjusted according to serum IGF-I and Fat Mass Percentage by DXA scan. An oral glucose tolerance test (OGTT) was performed at baseline (after GH discontinuation for 2–12 months; N=22) and at 1 and 2 years after GH re-start (n=40). IGT and T2DM were defined as glucose levels at 2 hours after glucose load between 7.8 and 11.0 or >11.0 mmol/l resp.

Results: After 2 years of GH, fasting insulin and HOMA-IR were significantly higher than at baseline (P=0.011 and P=0.009, resp.), but fasting glucose, glucose and insulin at 2 hours after glucose load and glucose and insulin AUC had not significantly changed. Of 22 patients, with an OGTT at baseline and after 2 years, one had IGT at baseline and at 2 years, one had T2DM which returned to IGT at 2 years and two patients had developed IGT after 2 years of GH. Four patients who did not have an OGTT at baseline had IGT at 2 years. None of 40 patients developed T2DM after 2 years of GH.

Conclusions: Two years of GH in young adults with Prader-Willi syndrome leads to higher fasting insulin levels, without changes in 2 hours glucose, insulin and AUC. Thus, GH reduces insulin sensitivity, but does not lead to diabetes mellitus in young adults with PWS.

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