Normalization of the IGF-IGFBP Axis by Sustained Nightly Insulinization in Type 1 Diabetes

Abstract

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 A1C. RESEARCH DESIGN AND METHODS—Twelve pubertal adolescents with type 1 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. A1C 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 GH 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.