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

Abstract

OBJECTIVE. To test the hypothesis that start of insulin Glargine with sustained nightly insulin action results in changes in circulating concentrations of IGF-I and IGFBPs in adolescents with type 1 diabetes mellitus (T1DM), changes that may support improvement of HbA1c.

RESEARCH DESIGN AND METHODS. Twelve pubertal adolescents with T1DM and initially on NPH insulin were studied during 12 weeks of intensified treatment with Glargine.

RESULTS. Subnormal IGF-I on NPH (- 1.8 ± 0.4 SDS) rapidly increased and remained 54 ± 9% elevated (P< 0.001) after 12 weeks on Glargine. HbA1c 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 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 GHBP), indicating that post-receptor 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 post-receptor 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.