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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

The Diabetes Prevention Trial-Type 1

¹ Division of Endocrinology, University of Miami, Miami, Florida
² Division of Endocrinology/Metabolism, University of Washington, Seattle, Washington
³ Benaroya Research Institute at Virginia Mason, Seattle, Washington
⁴ Department of Epidemiology and Biostatistics, University of Western Ontario, Ontario, Canada
⁵ National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health, Bethesda, Maryland
⁶ Division of Informatics and Biostatistics, University of South Florida, Tampa, Florida
⁷ Barbara Davis Center for Childhood Diabetes, Denver, Colorado
⁸ Department of Pediatric Endocrinology and Metabolism, Washington University in St. Louis, School of Medicine, St. Louis, Missouri
⁹ Department of Pediatric Endocrinology, Stanford University, Stanford, California
¹⁰ Division of Endocrinology, Columbia University, New York, New York
¹¹ Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida

Address correspondence and reprint requests to Jay M. Sosenko, MD, Division of Endocrinology, University of Miami, P.O. Box 016960 (D110), Miami, FL 33101. E-mail: jsosenko{at}med.miami.edu

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.

Abbreviations: AUC, area under the curve • DPT-1, Diabetes Prevention Trial-Type 1 • ICA, islet-cell autoantibody • OGTT, oral glucose tolerance test • ROC, receiver-operator curve

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				J. M. Sosenko, J. P. Krischer, J. P. Palmer, J. Mahon, C. Cowie, C. J. Greenbaum, D. Cuthbertson, J. M. Lachin, J. S. Skyler, and the Diabetes Prevention Trial-Type 1 Study Group A Risk Score for Type 1 Diabetes Derived From Autoantibody-Positive Participants in the Diabetes Prevention Trial-Type 1 Diabetes Care, March 1, 2008; 31(3): 528 - 533. [Abstract] [Full Text] [PDF]