Glucose Metabolism Evaluated by Glycated Hemoglobin and Insulin Sensitivity Indices in Children Treated with Recombinant Human Growth Hormone

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 during the first three years of treatment. Glucose metabolism was evaluated annually by oral glucose tolerance test (OGTT) and glycated hemoglobin A1c (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 dosages 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 a higher prevalence of IR (p<0.05). These indices did not alter further during the follow-up and were not related to GH dose or to family history of diabetes. A significant correlation was found only for IR indices and pubertal status, weight and age (p<0.05). Conclusion: In this retrospective study on a large GH deficient pediatric population, conventional use of replacement therapy resulted in an increase in HbA1c and IR after one year of therapy, regardless of rhGH dosage. These alterations did not worsen significantly in the following two years and were not associated with overt diabetes.