Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels

Abstract

Objective: We sought to determine whether an oral disposition index (DI(O)) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DI(O) 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 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 (DeltaI(0-30)/DeltaG(0-30)).

Results: DeltaI(0-30)/DeltaG(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 DeltaI(0-30)/DeltaG(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 DeltaI(0-30)/DeltaG(0-30) and 1/fasting insulin was calculated (DI(O)) and decreased from NGT to IFG/IGT to diabetes (P < 0.001). Among nondiabetic subjects at baseline, baseline DI(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(O) provides a measure of beta-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.

Figure 1

The computed slopes (——) and 95% CIs for the slopes (– – –) for ln(ΔI_0–30/ΔG_0–30) versus ln(1/fasting insulin) are plotted for subjects with NGT (slope −0.87 [95% CI −1.13 to −0.61]) (A), IGM (−0.84 [−1.05 to −0.63]) (B), and diabetes (DM) (−0.76 [−1.16 to −0.35]) (C). D: The hyperbolic curves for NGT, IGM, and diabetes, assuming a slope of −1, are plotted for ΔI_0–30/ΔG_0–30 versus 1/fasting insulin.

Figure 2

A: The DI_O (ΔI_0–30/ΔG_0–30 × 1/fasting insulin) decreases from NGT to IGM to diabetes (DM) (median [interquartile range]). B: The logarithmic means for baseline ΔI_0–30/ΔG_0–30 and 1/fasting insulin values are plotted for subjects with NGT (▪ and □) and IGM (• and ○) as nonprogressors (▪ and •) and progressors (□ and ○) relative to the hyperbolic curves. Progressors had lower β-cell function at baseline. C: The number of subjects who developed diabetes over the 10-year follow-up period by quintiles of baseline DI_O. D: ROC curves comparing ability of baseline ΔI_0–30/ΔG_0–30 (dotted line), 1/fasting insulin (dashed line), and DI_O (solid line) to predict cumulative diabetes at 10 years.