226-LB: HOMA-ß and ß-Cell Activity in Early and Late Phase during an OGTT Are Independent Risk Factors of Type 2 Diabetes in Japanese Americans

The β-cell plays a major role in type 2 diabetes (T2DM). HOMA-β reflects fasting β-cell activity. Insulin responses during an OGTT reflect β-cell activity during glucose loading, which has two phases, early and late. HOMA-β, early, and late β-cell activity have different pathophysiologies. However, no research has examined whether HOMA-β and early and late phase β-cell activity during an OGTT are independently associated with the risk of T2DM. In a prospective cohort study, 415 nondiabetic Japanese-American men and women were followed for 10-11 years. β-cell activity was assessed by HOMA-β [fasting insulin × 360/(fasting glucose − 63)] as fasting activity, the insulinogenic index (IGI) [?insulin (30-0 min)/?glucose (30-0 min)] during an OGTT as early phase activity, and (area under the curve (AUC) of insulin 60-120 min)/(AUC glucose 60-120 min) as late phase activity. Insulin sensitivity was estimated by Matsuda index [10000/square root of ((fasting glucose) × (fasting insulin) × (AUC glucose 0-120 min/120) × (AUC insulin 0-120 min/120))]. T2DM was diagnosed as fasting plasma glucose level ≥126 mg/dL, 2-hour glucose level ≥200 mg/dL, or taking glucose-lowering medications. During the 10-11 year follow-up, 95 cases of T2DM occurred. HOMA-β, IGI, and late phase β-cell activity were all independently associated with the risk of T2DM. Multiple-adjusted odds ratios of T2DM for tertile 1, 2, and 3 of HOMA-β were 1.00 (reference), 0.25 (95% CI, 0.11-0.57), and 0.14 (0.05-0.37), respectively; those of IGI were 1.00, 0.35 (0.17-0.75), and 0.19 (0.07-0.47), respectively; and those of late phase β-cell activity were 1.00, 0.34 (0.14-0.82), and 0.16 (0.05-0.53), respectively, in the model that included HOMA-β, IGI, late phase β-cell activity, Matsuda index, age, BMI, sex, and family history of T2DM.

In conclusion, higher β-cell activity while fasting and in both the early and late phase during an OGTT were all independently associated with a lower risk of T2DM.