Low levels of insulin-like growth-factor-binding protein-1 (IGFBP-1) are prospectively associated with the incidence of type 2 diabetes and impaired glucose tolerance (IGT): The Soderakra Cardiovascular Risk Factor Study

Aim. - To explore the association between baseline levels of insulin-like growth-factor-binding protein-1 (IGFBP-1), a marker of insulin sensitivity, and the development of type 2 diabetes or impaired glucose tolerance (IGT) in a specifically defined middle-aged population. Methods. - This cross-sectional population-based screening study was conducted in 1989-1990 and included baseline data for 664 non-diabetic subjects aged 40-59 years. Clinical data were collected and blood samples analyzed for blood glucose, serum lipids and insulin. Blood specimens were frozen at baseline and later analyzed for IGF-I, IGFBP-1 and C-reactive protein (CRP). At the follow-up in 2006, the incidence of type 2 diabetes and IGT was reported based on primary-care medical records. Results. - During the 17-year observation period, 42 subjects (6.3%) developed type 2 diabetes/IGT. Those in the lowest quintile of IGFBP-1 (<= 24 mu g/L) at baseline had a diabetes incidence of 12.6% while, in the highest quintile of IGFBP-1 (>= 59 mu g/L), the incidence was 1.5%. Cox's proportional-hazards model regression analyses were used to determine the incidence of type 2 diabetes/IGT, corrected for age and gender, in relation to IGFBP-1, CRP and waist circumference. Subjects in the lowest IGFBP-1 quintile showed an independently increased risk of type 2 diabetes/IGT [hazards ratio (HR): 3.54; 95% Cl 1.18-10.6; P = 0.024]. For CRP and waist circumference, the corresponding figures were HR: 6.81; 95% Cl 2.50-18.6; P < 0.001 and HR: 3.33; 95% Cl 1.47-7.6; P = 0.004, respectively. Conclusion. - Low levels of IGFBP-1 predicted the long-term development of type 2 diabetes or IGT in a middle-aged population. The association was independent of CRP and abdominal obesity. (C) 2009 Elsevier Masson SAS. All rights reserved.