Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels

OBJECTIVE - We sought to determine whether an oral disposition index (DIO) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DIO by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and beta-cell function. RESEARCH DESIGN AND METHODS - A total of 613 Japanese-American subjects (322 men and 291 women) underwent a 75-g Oral glucose tolerance test (OGTT) at baseline, 5 years, and 1.0 years. Insulin sensitivity was estimated as 1/fasting insulin or homeostasis model assessment of insulin sensitivity (HOMA-S). Insulin response Was estimated as the change in insulin divided by change in glucose from 0 to 30 min (Delta l(0-30)/Delta G(0-30)). RESULTS - Delta l(0-30)/Delta G(0-30) demonstrated a curvilinear relationship with 1/fasting insulin and HOMA-S With a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the log(e)-transformed estimates included -1 for Delta l(0-30)/Delta G(0-30) versus 1/fasting insulin for all glucose tolerance groups, consistent with a hyperbolic relationship. When HOMA-S was used as the insulin Sensitivity measure, the confidence limits for the slope included - I only for Subjects With normal glucose tolerance (NCT) or impaired fasting glucose (IFG/impaired glucose tolerance (IGT) but not diabetes. On the basis of this hyperbolic relationship, the product of Delta l(0-30)/Delta G(0-30) and 1/fasting insulin was calculated (DIO) and decreased fron NGT to IFG/IGT to diabetes (P < 0.001). Among nondiabetic subjects at baseline, baseline DIO predicted cumulative diabetes at 10 years (P<0.001) independent of age, sex, BMI, family history of diabetes, and baseline fasting and 2-h glucose concentrations. CONCLUSIONS- The DIO provides a measure of beta-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.