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

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

Address correspondence and reprint requests to Peter Bang, MD, PhD, Pediatric Endocrinology Unit Q2:08, Karolinska Institute, SE-171 76 Stockholm, Sweden. Email: peter.bang{at}ki.se

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.

Abbreviations: GH, growth hormone • GHBP, growth hormone binding protein • GHR, growth hormone receptor • IGFBP, IGF binding protein • IGFBP-3-PA, IGFBP-3 proteolysis • MIT, mealtime insulin therapy • SOCS, suppressors of cytokine signaling

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