β-cell dysfunction is major risk factor for type 2 diabetes. As HOMA-β reflects fasting β-cell function and insulinogenic index reflects early phase insulin response during an oral glucose tolerance test (OGTT), these two indices represent different aspects of insulin and glucose metabolism. It is not known whether HOMA-β and insulinogenic index are independently associated with type 2 diabetes risk. In a prospective cohort study, 415 nondiabetic Japanese-American men and women were followed for 10-11 years. Insulin sensitivity was assessed by HOMA-IR. β-cell activity was assessed by HOMA-β [fasting plasma insulin (μU/mL) × 360/(fasting plasma glucose (mg/dL) - 63)] and the insulinogenic index [Δinsulin (30-0 min) (μU/mL)/Δglucose (30-0 min) (mg/dL)] obtained during a 75-g OGTT. Type 2 diabetes was diagnosed as fasting plasma glucose level ≥126 mg/dL, 2-hour glucose level ≥200 mg/dL, or taking glucose-lowering medications. Logistic regression analysis was used to estimate odds ratios (OR) of incident diabetes. A total of 95 participants developed type 2 diabetes over 10-11 years. Insulinogenic index and HOMA-β were independently associated with the risk of type 2 diabetes. In multiple-adjusted models that included insulinogenic index, HOMA-β, HOMA-IR, age, BMI, gender, and family history of diabetes, OR of future type 2 diabetes for tertile 2 and 3 of insulinogenic index were 0.43 (95% CI, 0.22-0.85) and 0.31 (0.14-0.67), respectively, compared to tertile 1, and those for tertile 2 and 3 of HOMA-β were 0.31 (0.14-0.69) and 0.25 (0.10-0.63), respectively, compared to tertile 1. HOMA-IR was also associated with the risk of type 2 diabetes independent of these two indices. OR of tertile 2 and 3 of HOMA-IR were 1.75 (0.82-3.74) and 9.17 (3.78-22.28), respectively, compared to tertile 1.
In conclusion, both higher insulinogenic index and HOMA-β were independently associated with a lower risk of type 2 diabetes independent of insulin sensitivity.
K.K. Sato: None. T. Hayashi: None. S. Uehara: None. Y. Onishi: None. D.L. Leonetti: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. W.Y. Fujimoto: None. E.J. Boyko: None.