Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study

Lancet. 2002 May 18;359(9319):1740-5. doi: 10.1016/S0140-6736(02)08655-5.

Abstract

Background: Results of experimental and clinical studies suggest that insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) could be important determinants of glucose homoeostasis. However, experimental models might also reflect compensatory and adaptive metabolic processes. We therefore prospectively examined the associations between circulating concentrations of IGF-I and IGFBP-1 and development of glucose tolerance.

Methods: Participants in this cohort study were a random sample of 615 normoglycaemic men and women aged 45-65 years. Participants underwent oral glucose tolerance testing based on WHO definitions and criteria in 1990-92 and 1994-96. At the baseline visit, we measured serum concentrations of IGF-I and IGFBP-1, and assessed the relation between these peptides and subsequent glucose intolerance.

Findings: At 4.5 years of follow-up, 51 (8%) of 615 participants developed impaired glucose tolerance or type-2 diabetes. After adjustment for correlates of IGF-I and risk factors for glucose intolerance, the odds ratio for risk of impaired glucose tolerance or type-2 diabetes for participants with IGF-I concentrations above the median (> or = 152 microg/L) compared with those with concentrations below the median (<152 microg/L) was 0.50 (0.26-0.95). Consistent with this finding, IGF-I also showed a significant inverse association with subsequent 2-h glucose concentrations, which was independent of correlates of IGF-I and risk factors for glucose tolerance (p for linear trend=0.026). We also found that this inverse association was independently modified by IGFBP-1 (p for interaction=0.011).

Interpretation: These data show that circulating IGF-I and its interaction with IGFBP-1 could be important determinants of glucose homoeostasis and provide further evidence for the possible protective role of IGF-I against development of glucose intolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / metabolism*
  • Fasting / metabolism
  • Female
  • Glucose Intolerance / diagnosis
  • Glucose Intolerance / metabolism*
  • Homeostasis
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Middle Aged
  • Prospective Studies

Substances

  • Blood Glucose
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor I