Utility of C-peptide for a reliable estimate of insulin secretion in children with growth hormone deficiency

Objective: GH treatment (GHT) can lead to glucose metabolism impairment through decreased insulin sensitivity and impaired pancreatic beta-cell function, which are the two key components of the pathogenesis of diabetes. Therefore, in addition to insulin sensitivity, during GHT it is very important to perform a reliable evaluation of insulin secretion. However, conflicting data exist regarding the insulin secretion in children during GHT. C-peptide provides a more reliable estimate of beta-cell function than insulin, but few studies evaluated it during GHT. Our aim was to assess the usefulness of C-peptide in the evaluation of insulin secretion in GH deficiency (GHD) children. Design: In 48 GHD children, at baseline and after 12 and 24 months of GHT, and in 56 healthy subjects we evaluated fasting and glucagon-stimulated (AUC(Cpep)) C-peptide levels in addition to other commonly used secretion indexes, such as fasting and oral glucose tolerance test-stimulated insulin levels (AUC(INS)), Homa-beta, and insulinogenic index. The main outcomes were the change in C-peptide during GHT and its correlation with the auxological and hormonal parameters. Results: At baseline GHD children showed a significant lower AUC(Cpep) (p = 0.006), while no difference was found for the other indexes. Both fasting C-peptide (beta 0307, p = 0.016) and AUC(Cpep) (beta 0379, p = 0.002) were independently correlated with IGF-I SDS, while no correlation was found for all other indexes. After 12 months an increase in Homa-beta (p < 0.001), fasting C-peptide (p = 0.002) and AUC(Cpep) (p<0.001) was found. At multivariate analysis, only fasting C-peptide (beta 0.783, p = 0.001) and AUC(Cpep) (beta 0.880, p < 0.001) were independently correlated with IGF-I SDS. Conclusions: C-peptide, rather than the insulin-derived indexes, has proved to be the most useful marker of insulin secretion correlated to IGF-I levels in GHD children. Therefore, we suggest the use of glucagon test both as diagnostic test for the GH assessment and as a useful tool for the evaluation of insulin secretion during GHT in children. (C) 2016 Elsevier Ltd. All rights reserved.