Residual β-cell function and the insulin-like growth factor system in Danish children and adolescents with type 1 diabetes

Context: C-peptide positive adults with type 1 diabetes (T1D) have higher circulating total and free IGF-I and lower IGF binding protein 1 (IGFBP-1) than C-peptide negative patients. Whether this is also the case in children remains unknown. Objective: To examine the IGF-system in children/adolescents with and without residual beta-cell function (RBF). Design and Patients: Cross-sectional study containing 136 pre-pubertal (hereof 15 RBF-positive) and 206 pubertal (hereof 42 RBF-positive) children/adolescents with T1D for 3-6 years as well as 40 pre-pubertal and 30 pubertal healthy controls. RBF was evaluated by meal-stimulated C-peptide. Main Outcome Measures: Fasting serum levels of bioactive IGF (i.e. the ability of serum to activate the IGF-I receptor in vitro), total IGF-I, total IGF-II, and IGFBP-1 and -3. Results: Irrespective of pubertal status, patients with T1D showed lower bioactive IGF and total IGF-I, but higher IGFBP-1 as compared to controls (P<0.05). When stratified according to RBF-status, a positive RBF was associated with normalization of all IGF-related peptides but IGFBP-1 in pre-pubertal children, (P <0.05), whereas none of the IGF-components were normalized in pre-pubertal, RBF-negative children. In pubertal children, total IGF-I and bioactive IGF remained subnormal and IGFBP-1 supranormal, irrespective of RBF status (P<0.05). Conclusion: Independent of pubertal status, T1D was associated with an abnormal IGF-system. However, a positive RBF-status appeared important, but only in pre-pubertal children, in whom all IGF-components but IGFBP-1 were normalized. We speculate that the pubertal GH-surge induces insulin-resistance, which overrides the stimulatory effect that an RBF may exert on the liver-derived IGF-system.