Dose-dependent effects of recombinant human insulin-like growth factor (IGF)-I/IGF binding protein-3 complex on overnight growth hormone secretion and insulin sensitivity in type 1 diabetes

J Clin Endocrinol Metab. 2004 Sep;89(9):4634-41. doi: 10.1210/jc.2004-0243.


GH hypersecretion in type 1 diabetes has been implicated in the pathogenesis of insulin resistance, and microangiopathic complications, and may result from reduced circulating IGF levels. We examined the effects of recombinant human (rh)IGF-I [complexed in equimolar ratio with rhIGF binding protein (BP)-3 (rhIGF-I/IGFBP-3)] replacement on overnight GH levels and insulin sensitivity in type 1 diabetes. Fifteen subjects, 13-24 yr old (10 male), were given rhIGF-I/IGFBP-3 or placebo as a daily sc injection for 2 d. After the second injection overnight, insulin requirements for euglycemia were determined (0400-0800 h), followed by a 4-h, two-step (insulin, 0.6 and 1.5 mU/kg.min) hyperinsulinemic euglycemic [90 mg/dl (5 mmol/liter)] clamp. In each subject, the protocol was repeated on three occasions in random order. Seven subjects received placebo and rhIGF-I/IGFBP-3 (0.1 mg/kg.d and 0.4 mg/kg.d), and eight subjects received placebo and rhIGF-I/IGFBP-3 (0.2 mg/kg.d and 0.8 mg/kg.d). We found dose-dependent increases in circulating IGF-I and IGFBP-3 concentrations after rhIGF-I/IGFBP-3. These were paralleled by significant reductions in mean overnight GH levels and GH pulse amplitude. We also observed dose-dependent effects of rhIGF-I/IGFBP-3 on overnight insulin requirements for euglycemia, with reductions of up to 41%. Insulin sensitivity, defined by M-values, was improved with rhIGF-I/IGFBP-3 (0.4 and 0.8 mg/kg.d). Thus, restoration of circulating IGF-I and IGFBP-3 levels with rhIGF-I/IGFBP-3 suppresses GH secretion in adolescents with type 1 diabetes, leading to reduced insulin requirements and improvements in insulin sensitivity.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / analysis
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / metabolism*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Human Growth Hormone / metabolism*
  • Humans
  • Insulin / blood
  • Insulin / pharmacology*
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / pharmacology*
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / pharmacology*
  • Male
  • Recombinant Proteins / pharmacology
  • Sex Characteristics


  • Blood Glucose
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 3
  • Recombinant Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I