Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor-Binding Protein 3 in Relation to the Risk of Type 2 Diabetes Mellitus: Results From the EPIC-Potsdam Study

Am J Epidemiol. 2016 Mar 15;183(6):553-60. doi: 10.1093/aje/kwv188. Epub 2016 Feb 14.


Higher levels of insulin-like growth factor-binding protein 3 (IGFBP-3) might raise the risk of type 2 diabetes mellitus (T2DM) via binding of insulin-like growth factor 1 (IGF-1), an insulin-like hormone that is involved in glucose homeostasis. We investigated serum concentrations of IGF-1 and IGFBP-3 and their molar ratio in relation to T2DM incidence in a nested case-cohort study within the European Prospective Investigation Into Cancer and Nutrition-Potsdam Study. We included a randomly selected subcohort of persons without T2DM at the time of blood sampling (n = 2,269) and 776 individuals with incident T2DM identified between 1994 and 2005. For the highest quartile versus lowest, the multivariable-adjusted hazard rate ratios were 0.91 (95% confidence interval (CI): 0.68, 1.23; P for trend = 0.31) for IGF-1, 1.33 (95% CI: 1.00, 1.76; P for trend = 0.04) for IGFBP-3, and 0.77 (95% CI: 0.57, 1.03; P for trend = 0.03) for IGF-1:IGFBP-3 ratio. IGFBP-3 level remained positively associated with T2DM incidence-and the ratio of IGF-1 to IGFBP-3 was inversely related with T2DM incidence--in models that included adjustment for IGF-1 concentrations (P for trend < 0.05). Therefore, our findings do not confirm an association between total IGF-1 concentrations and risk of T2DM in the general study population, although higher IGFBP-3 levels might raise T2DM risk independent of IGF-1 levels.

Keywords: insulin-like growth factor 1; insulin-like growth factor–binding protein 3; prospective study; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Europe / epidemiology
  • Female
  • Humans
  • Incidence
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Surveys and Questionnaires


  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I