Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men

Abstract

Aims/hypothesis: Insulin-like growth factor-binding protein-1 (IGFBP-1) production in the liver is inhibited by insulin, and low circulating levels are associated with the metabolic syndrome. The aim of this study was to evaluate the predictive role and change in IGFBP-1 concentrations during development of abnormal glucose regulation.

Methods: IGFBP-1 levels were determined at baseline and at 10 years in an incident case-control prospective study of Swedish white men aged 35-56 years. Individuals with normal glucose tolerance at baseline who developed abnormal glucose tolerance during a 10 year period (n = 355) according to WHO criteria were pair-matched to controls for age and family history of diabetes.

Results: Fasting IGFBP-1 concentrations were lower in individuals who later developed abnormal glucose regulation and correlated inversely with fasting proinsulin values (r = -0.48; p < 0.0001), and both were significant predictors. Individuals in the highest quartile at baseline for an algorithm incorporating fasting IGFBP-1, blood glucose, proinsulin and waist and height had a 40-fold increased risk of developing type 2 diabetes compared with the lowest quartile (95% CI 7.7-214). IGFBP-1 increased 32% (95% CI 17-49%) during the 10 years in those developing diabetes and was increased in relation to insulin levels, suggesting the emergence of hepatic insulin resistance. Moreover, elevated IGFBP-1 levels at follow-up were associated with higher 2 h glucose values during an OGTT.

Conclusions/interpretation: Low IGFBP-1 predicts the development of abnormal glucose regulation and, as an inhibitor of the insulin-like actions of insulin-like growth factors, elevated levels of IGFBP-1 after the development of diabetes may also play a pathophysiological role.