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OBJECTIVE - We sought to determine whether an oral disposition index (DI^sub O^) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DI^sub O^ by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and ß-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 10 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 (ΔI^sub 0-30^/ΔG^sub 0-30^).
RESULTS - ΔI^sub 0-30^/ΔG^sub 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^sub e^-transformed estimates included - 1 for ΔI^sub 0-30^/ΔG^sub 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 - 1 only for subjects with normal glucose tolerance (NGT) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) but not diabetes. On the basis of this hyperbolic relationship, the product of ΔI^sub 0-30^/ΔG^sub 0-30^ and 1/fasting insulin was calculated (DI^sub O^) and decreased from NGT to IFG/IGT to diabetes (P < 0.001). Among nondiabetic subjects at baseline, baseline DI^sub O^ 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 DI^sub O^ provides a measure of ß-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.
Diabetes Care 32:335-341, 2009
Type 2 diabetes is characterized by both insulin resistance and ß-cell dysfunction (1). Abnormalities in ß-cell function are present in high-risk individuals long before they develop by- perglycemia (1). This recognition has occurred in part because of a better understanding of the ability of the ß-cell to regulate its insulin response to stimuli based on differences in insulin sensitivity.
Using intravenous testing, subjects with normal ß-cell function demonstrate a hyperbolic relationship between insulin sensitivity...