Normalization of the IGF-IGFBP axis by sustained nightly insulinization in type 1 diabetes

OBJECTIVE - We sought to test the hypothesis that start of insulin glargine with sustained nightly insulin action results in changes in circulating concentrations of IGF-I and IGF binding proteins (IGFBPs) in adolescents with type 1 diabetes-changes that may support improvement of AlC. RESEARCH DESIGN AND METHODS - Twelve pubertal adolescents with type I diabetes and initially on NPH insulin were studied during 12 weeks of intensified treatment with glargine. RESULTS - Subnormal IGF-I SD scores on NPH (- 1.8 +/- 0.4) rapidly increased and remained 54 +/- 9% elevated (P < 0.001) after 12 weeks on glargine. AlC decreased from 8.3 0.6% to a nadir of 6.9 +/- 0.3% (P = 0.002) at 6 weeks and correlated with changes in IGF-I (r -0.64, P < 0.05). The increase in IGF-I did not suppress the mean overnight growth hormone (GH) secretion at 6 weeks. The mean overnight IGFBP-1 levels decreased (P = 0.035), supporting the hypothesis that the nightly hepatic insulin action was increased. Circulating IGF-I increased in the absence of changes in both G1I secretion and GH receptor numbers (assessed by growth hormone binding protein), indicating that postreceptor mechanisms are involved. IGFBP-3 proteolysis was decreased. CONCLUSIONS - increased hepatic insulin action after start of glargine was evident from a decrease in night time IGFBP-1 concentrations. This may improve GH postreceptor signaling, resulting in increased circulating IGF-I. We suggest that even in the absence of changes in GH, increased IGF-I and decreased IGFBP-1 support the improvement of metabolic control.