Glucose Metabolism Evaluated By Glycated Hemoglobin And Insulin Sensitivity Indexes In Children Treated With Recombinant Human Growth Hormone

Abstract

Objective: To evaluate glucose metabolism and insulin sensitivity in children with idiopathic growth hormone (GH) deficiency treated with recombinant human GH (rhGH) and to identify possible risk factors for the development of glucose abnormalities in this population. Methods: We retrospectively collected data from 101 patients (60 males, median age 10.4 years, 77 prepubertal), with confirmed GH deficiency, enrolled before starting rhGH and followed up for the first three years of treatment. Glucose metabolism was evaluated every year by oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c). OGTT was used to calculate insulin sensitivity (HOMA-S) and insulin resistance (HOMA-IR), defined as HOMA-IR>3. Results: RhGH was effective in improving growth and its dosage was significantly reduced after the first year of therapy. No patient developed diabetes mellitus. After one year of therapy, a significant increase in HbA1c (p=0.0042) and insulin levels (fasting p<0.0001, 60 min p=0.0018, 120 min p=0.0003) was observed, with higher prevalence of insulin resistance (p<0.05 for HOMA-IR). These indexes did not alter further during the follow-up and were not related to GH doses or to familiarity for diabetes. A significant correlation was found only for insulin resistance indexes and pubertal status, weight and age (p<0.05). Conclusions:In this retrospective study on a large GH deficient pediatric population, conventional use of replacement therapy resulted in an increase in HbA1c and insulin resistance after one year of therapy, regardless of rhGH dosage. These alterations were transient and not associated with significant changes in glucose metabolism during the subsequent follow-up. What is already known on this topic?Growth hormone plays an anti-insulin effect. Children treated with recombinant human GH (rhGH) may develop abnormalities in glucose metabolism, and present a higher incidence of type-2 diabetes mellitus, particularly in subjects with predisposing conditions such as obesity or positive family history. What this study adds?In this study, conventional use of rhGH, in a large GH deficient pediatric population, resulted in increased HbA1c and worsened insulin sensitivity after one year of therapy, although, at the subsequent follow-up, these indexes had not deteriorated further and were not associated with significant changes in glucose metabolism. This therapy proved to be safe, even in subjects considered at risk for glucose metabolism alteration.

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“…The OGTT insulin response was increased in both dose groups after 208 weeks of treatment. All changes in glucose metabolism were within the expected range when administering GH, which is known to induce a mild form of insulin resistance [41].…”