The Role of Insulin Resistance in Predicting the Progression to Type 1 Diabetes

Abstract

Objective -- To determine if insulin resistance is a risk factor for developing Type 1 Diabetes in autoantibody poisitve first-degree relatives of diabetic family members.

Research Design and Methods -- Subjects (n=186) who had a projected 25% to 50% risk for diabetes and subjects (n=170) who had a projected >50% risk for Type 1 Diabetes in five years were followed as part of the DPT-1 study to clinical diabetes onset or the end of the study. We assessed insulin secretion with first phase insulin response (FPIR), and insulin resistance with HOMA-R from the IVGTT. The median follow-up was 4.3 years for moderate risk subjects and 3.7 years for high risk subjects.

Results -- 53 subjects in the moderate risk group and 70 subjects in the high risk group developed Type 1 Diabetes during the follow-up period. After adjusted for confounders by using multivariate analysis, HOMA-R and FPIR/HOMA-R ratio were significantly associated with Type 1 Diabetes in both risk groups. In the moderate risk population, the hazard ratio of HOMA-R was 2.70(95% CI: 1.45-5.06) and the hazard ratio of FPIR/HOMA-R was 0.32 (95% CI: 0.18-0.57). In the high risk population, the hazard ratio of HOMA-R was 1.83 (95% CI: 1.19-2.82) and FPIR/HOMA-R was 0.56(95% CI: 0.40-0.78).

Conclusions -- There is clear evidence of the association between insulin resistance and the progression to Type 1 Diabetes. The combination of FPIR and HOMA-R could be used as a better metabolic indicator for Type 1 Diabetes risk in prediction and suggest possible intervention strategies for diabetes prevention.