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

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-1 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 (≥152 μg/L) compared with those with concentrations below the median (<152 μg/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.