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

¹Pediatric Endocrinology Unit, Department of Woman and Child Health
²CLINTEC, Karolinska Institute, Stockholm, Sweden

peter.bang{at}ki.se

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.

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