Reduction in insulin sensitivity and inadequate β-cell capacity to counteract the increase in insulin resistance in children with idiopathic growth hormone deficiency during 12 months of growth hormone treatment

Purpose: To evaluate the performance of various indexes of insulin sensitivity and secretion and to identify the most useful indicator of deterioration of glucose metabolism in a cohort of children with growth hormone (GH) deficiency (GHD) during GH treatment. Methods: In 73 GHD children (55 M, 18 F; mean age 10.5 years) at baseline and after 12 months of treatment, we evaluated a number of surrogate indexes of insulin secretion and sensitivity. In a subgroup of 11 children we also performed an euglycemic hyperinsulinemic clamp. Results: After 12 months, a significant increase in fasting glucose (p < 0.001) and HbA1c levels (p < 0.001) was documented, despite all children remained with a normal glucose tolerance. With regard the insulin secretion, Homa-β did not show any significant change (p = 0.073), while oral disposition index (DIo) showed a significant decrease (p = 0.031). With regard the insulin sensitivity, Homa-IR significantly increased (p < 0.001) with a concomitant decrease in QUICKI (p < 0.001). ISI Matsuda showed a decrease, although not statistically significant (p = 0.069). In the subgroup of 11 children, the M value derived from clamp showed a significant decrease (p = 0.011) and a significant positive correlation was found between M value and ISI Matsuda both at baseline (ρ 0.950; p = 0.001) and after 12 months (ρ 0.980; p = 0.001) but not with Homa-IR and QUICKI. Conclusions: 12 months of GH treatment lead to a decrease in insulin sensitivity and impairment in insulin secretion relative to insulin sensitivity even without evident changes in glucose tolerance. DIo has proven to be the most useful indicator of deterioration of glucose metabolism even in cases in which the overt glucose abnormalities have not yet appeared.