Long-acting Insulin Analogs Effect on gh/igf Axis of Children with Type 1 Diabetes: a Randomized, Open-label, Two-period, Cross-over Trial

Background: Growth hormone (GH) secretion is increased in pre-pubertal children with type 1 diabetes and GH excess produces insulin resistance. Early-morning insulinopenia contributes to lower insulin-like growth factor (IGF-I) levels and to GH hypersecretion. Objective: To evaluate differences in GH/IGF-I axis of pre-pubertal children with type 1 diabetes treated with glargine or detemir as long-acting insulin analogues, which was the main outcome measure, and to compare insulin effects in obtaining good metabolic control. Subjects: Children with type 1 diabetes. Methods: This was a 32-week, randomized, open-label, two-period, cross-over comparison between bedtime glargine and twice-daily detemir insulin, involving pre-pubertal children in care at a diabetes pediatric centre. After a 8-week-run-in period subjects were randomized to bedtime glargine or twice-daily detemir insulin administration. After a 12-week period treatments were inverted and continued for additional 12 weeks. Results: Overall, 15 pre-pubertal children (53.3 % males, mean age 8.6 +/- 1.5 years, duration of diabetes 4.2 +/- 1.5 years) completed the study. Groups did not differ for GH/IGF axis and HbA1c levels. Treatment with glargine was associated with lower fasting glucose values than treatment with detemir (8.1 +/- 1.5 vs. 8.2 +/- 1.7 mmol/L, p = 0.01). Incidence rate of hypoglycemia was not different between insulin treatments (IRR = 1.18, 95 % CI 1.00-1.38; p = 0.07). Detemir treatment was associated with a higher increase in body weight (p = 0.008) and height (p = 0.02) when compared with glargine. Conclusion: Detemir and glargine not show significant differential effects on the GH/IGFI axis. The greater weight gain and height associated with detemir treatment, apparently not related to the level of pubertal growth, deserve further investigation.