Role of Insulin Resistance in Predicting Progression to Type 1 Diabetes

OBJECTIVE — The purpose of this study was to determine whether insulin resistance is a risk factor for the development of type 1 diabetes in autoantibody-positive first-degree relatives of diabetic family members. RESEARCH DESIGN AND METHODS — Subjects (n 186) who had a projected 25–50 % risk for diabetes and subjects (n 170) who had a projected 50 % risk for type 1 diabetes in 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial–Type 1. We assessed insulin secretion with the first-phase insulin response (FPIR) and insulin resistance with homeostasis model assessment of insulin resistance (HOMA-IR) from an intravenous glucose tolerance test. The median follow-up was 4.3 years for moderate-risk subjects and 3.7 years for high-risk subjects. RESULTS — During the follow-up period, 53 subjects in the moderate-risk group and 70 subjects in the high-risk group developed type 1 diabetes. After adjustments for confounders using multivariate analysis, HOMA-IR and the FPIR–to–HOMA-IR ratio were significantly asso-ciated with type 1 diabetes in both risk groups. In the moderate-risk population, the hazard ratio (HR) of HOMA-IR was 2.70 (95 % CI 1.45–5.06) and the HR of FPIR-to-HOMA-IR was 0.3