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 ␤-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 (⌬I 0 -30 /⌬G 0 -30 ).RESULTS -⌬I 0 -30 /⌬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 Ϫ1 for ⌬I 0 -30 /⌬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 Ϫ1 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 ⌬I 0 -30 /⌬G 0 -30 and 1/fasting insulin was calculated (DI O ) and decreased from NGT to IFG/IGT to diabetes (P Ͻ 0.001). Among nondiabetic subjects at baseline, baseline DI O predicted cumulative diabetes at 10 years (P Ͻ 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 ␤-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.

Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies

“…Early onset of GDM (weeks [16][17][18][19][20] was found in 40% of subjects with GDM and normal BMI when tested with 75 g OGTT (4). In the early-onset group, significant reductions in b-cell function were found, as well as decreases in insulin sensitivity.…”

“…glucose tolerance tests (6). Recently, the hyperbolic relationship of b-cell function and insulin sensitivity has also been demonstrated with data obtained from OGTT results in nonpregnant individuals (17,18), and this relationship has not been tested in pregnancy. In pregnant women in late gestation (weeks [24][25][26][27][28], b-cell function adjusted for insulin sensitivity deteriorated markedly when impaired glucose tolerance (IGT) and GDM individuals were compared with normal glucose tolerance (NGT) individuals, and most so in GDM (19).…”

Impact of impaired insulin secretion and insulin resistance on the incidence of diabetes in a Japanese cohort

“…The failure to find high PAF values for the 'IIS plus IR' group, which had the highest HR for incidence of diabetes, may well be due to the fact that the number of participants in this category was small. Furthermore, if beta cell function, as measured by oral disposition index [7], had been used instead of glucose-stimulated insulin secretion, this would have been a stronger predictor of the incidence of diabetes.…”

High normal fasting glucose level in obese youth: a marker for insulin resistance and beta cell dysregulation

“…It has been demonstrated that impaired fasting glucose (IFG) is a clinical condition associated with a threefold increased risk of developing type 2 diabetes mellitus [3][4][5][6][7], and IFG status acts as a good marker of the acute insulin response and the disposition index (DI) [8,9]. Although the established thresholds for defining IFG may be considered to be quite low, recent reports have suggested that fasting plasma glucose (FPG) within the normal range (NFPG) is a significant risk factor for future development of type 2 diabetes mellitus in adults [3][4][5][6][7].…”