Insulin Resistance, β-Cell Dysfunction, and Conversion to Type 2 Diabetes in a Multiethnic Population: The Insulin Resistance Atherosclerosis Study

OBJECTIVE: Insulin resistance and β-cell function are major predictors of type 2 diabetes, but studies using direct methods of insulin resistance and secretion are few and relatively small. Furthermore, the strength of these associations has not been tested in different ethnic groups and various states of glucose tolerance, family history of diabetes, and obesity. RESEARCH DESIGN AND METHODS: Predictors of incident diabetes were evaluated in Hispanic, non-Hispanic white, and African American participants in the Insulin Resistance Atherosclerosis Study (aged 40–69 years). In 557 participants with normal glucose tolerance and 269 with impaired glucose tolerance (IGT), insulin sensitivity (insulin sensitivity index [S(I)]) and first-phase insulin secretion (acute insulin response [AIR]) were directly measured using the frequently sampled intravenous glucose tolerance test. RESULTS: At the 5-year follow-up examination, 128 (15.5%) individuals had developed diabetes. Both S(I) (odds ratio × 1 SD 0.50 [95% CI 0.37–0.68]) and AIR (0.51 [0.40–0.65]) were independent predictors of incident diabetes even after adjustment for age, sex, ethnicity, center, IGT, family history of diabetes, and BMI. The strength of the relation of S(I) and AIR to incident diabetes was not significantly affected by potential interactions of age, sex, ethnicity, glucose tolerance, BMI, or family history of diabetes (P ≥ 0.15). CONCLUSIONS: Both insulin sensitivity and β-cell function predict conversion to diabetes in different ethnic groups and various states of glucose tolerance, family history of diabetes, and obesity. The prevention of type 2 diabetes should focus on interventions that improve both insulin resistance and insulin secretion.