Progression of insulin resistance: A link between risk factors and the incidence of diabetes.

AIMS

Insulin resistance (IR) changes over time during the development of type 2 diabetes. Some reports showed that obesity was associated with progression of IR. However, no study has explored if change of IR predicts incident diabetes, and no study has investigated other factors associated with the change.

METHODS

In this study, 1184 subjects without diabetes at baseline were enrolled in 2006-2016 with a median follow-up period of 4.5 years. Diabetes was diagnosed by oral glucose tolerance test and hemoglobin A1c, or if anti-diabetic agents were used. HOMA2-IR and ISI were used to estimate IR.

RESULTS

The annual changes of HOMA2-IR(ΔHOMA2-IR/year) and ISI(ΔISI/year) were associated with BMI, waist circumference(WC), glucose, HbA1c, triglyceride and HDL-cholesterol. Subjects with pre-diabetes or metabolic syndrome were associated with a more rapid increase of IR. ΔHOMA2-IR/year and ΔISI/year were correlated with annual changes of BMI and WC. The hazard ratios for ΔHOMA2-IR/year and ΔISI/year to predict incident diabetes were 1.39 (95% CI 1.22-1.59, p < 0.001) and 0.13 (95% CI 0.09-0.19, p < 0.001) in adjusted models, respectively.

CONCLUSIONS

Change of IR can be used as a surrogate marker of incident diabetes. The progression of IR is an important pathophysiologic link between risk factors and the incidence of diabetes.