Objective: To evaluate glucose metabolism and insulin sensitivity in children with idiopathic growth hormone (GH) deficiency, treatedwith 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 GHdeficiency, enrolled before starting rhGH and followed up during the first three years of treatment. Glucose metabolism was evaluatedannually 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 developeddiabetes mellitus. After one year of therapy, a significant increase in HbA1c (p=0.0042) and insulin levels (fasting p<0.0001, 60 minp=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 thefollow-up and were not related to GH dose or to family history of diabetes. A significant correlation was found only for IR indices andpubertal 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 inan increase in HbA1c and IR after one year of therapy, regardless of rhGH dosage. These alterations did not worsen significantly in thefollowing two years and were not associated with overt diabetes.