Increasing the Accuracy of Oral Glucose Tolerance Testing and Extending Its Application to Individuals With Normal Glucose Tolerance for the Prediction of Type 1 Diabetes

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Abstract
OBJECTIVE—We assessed the extent to which both standard and alternative indexes from 2-h oral glucose tolerance testing predict type 1 diabetes and whether oral glucose tolerance tests (OGTTs) predict type 1 diabetes in individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS—The prediction of type 1 diabetes from baseline OGTTs was studied in 704 Diabetes Prevention Trial-Type 1 participants (islet-cell autoantibody [ICA]-positive relatives of type 1 diabetic patients). The maximum follow-up was 7.4 years. Analyses utilized receiver-operator curves (ROCs), proportional hazards models, and survival curves. RESULTS—ROC areas under the curve (ROCAUCs) for both the AUC glucose (0.73 ± 0.02) and an OGTT prediction index (0.78 ± 0.02) were higher (P < 0.001) than those for the fasting (0.53 ± 0.02) and 2-h glucose (0.66 ± 0.02). ROCAUCs for the 60- and 90-min glucose (0.71 ± 0.02 and 0.72 ± 0.02, respectively) were also higher (P < 0.01) than those for the fasting and 2-h glucose. Among individuals with normal glucose tolerance, OGTTs were highly predictive, with 4th versus 1st quartile hazard ratios for the 2-h glucose, AUC glucose, and OGTT prediction index ranging from 3.77 to 5.30 (P < 0.001 for all). CONCLUSIONS—Certain alternative OGTT indexes appear to better predict type 1 diabetes than standard OGTT indexes in ICA-positive relatives of type 1 diabetic patients. Moreover, even among those with normal glucose tolerance, OGTTs are strongly predictive. This suggests that subtle metabolic abnormalities are present several years before the diagnosis of type 1 diabetes.