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Patterns of Metabolic Progression to Type 1 Diabetes in 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, Virginia Mason Medical Center, Seattle, Washington
⁴ Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
⁵ National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
⁶ H. Lee Moffitt Cancer Center and Research Institute, University of Southern Florida, Tampa, Florida
⁷ Barbara Davis Center for Childhood Diabetes, Denver, Colorado
⁸ Division of Pediatric Endocrinology & Metabolism, Washington University School of Medicine, St. Louis, Missouri
⁹ Division of Pediatric Endocrinology, Stanford University, Palo Alto, California
¹⁰ Division of Endocrinology, Columbia University, New York, New York

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

OBJECTIVE—There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal of this study was to utilize data from the Diabetes Prevention Trial–Type 1 (DPT-1) to obtain a picture of the metabolic progression to type 1 diabetes over a period of approximately 2.5 years before its diagnosis.

RESEARCH DESIGN AND METHODS—Fifty-four DPT-1 participants (22 in the parenteral trial and 32 in the oral trial) were studied. All had oral glucose tolerance tests (OGTTs) at 6-month intervals from approximately 30 to 6 months before diagnosis. The vast majority also had OGTTs at diagnosis. Changes in OGTT glucose and C-peptide indexes from 30 to 6 months before diagnosis were examined by calculating slopes of the indexes for each individual over that time period. Changes from 6 months before diagnosis to diagnosis were examined by paired comparisons of the OGTT metabolic indexes between the time points.

RESULTS—Glucose levels increased gradually from 30 to 6 months before diagnosis in both the parenteral and oral groups (P < 0.001 for all indexes). Area under the curve (AUC) C-peptide (P < 0.05) and AUC C-peptide–to–AUC glucose ratio (P < 0.001) values decreased in the oral group; peak C-peptide–to–2-h glucose ratio values decreased in both groups (P < 0.001). In participants who also had OGTTs at diagnosis, AUC C-peptide (parenteral group, P < 0.05) and peak C-peptide (oral group, P < 0.05) values decreased from the last 6 months before diagnosis; stimulated C-peptide–to–glucose ratio values decreased in both groups (P < 0.001). Conversely, fasting C-peptide levels increased in both groups (oral group, P < 0.01). Fasting C-peptide–to–fasting glucose ratio values remained constant throughout the 30-month follow-up.

CONCLUSIONS—These data indicate that over a period of at least 2 years, glucose tolerance gradually deteriorates as stimulated C-peptide levels slowly decline in a substantial number of individuals who develop type 1 diabetes. However, fasting C-peptide levels are maintained, even at diagnosis.

Abbreviations: AUC, area under the curve • DPT-1, Diabetes Prevention Trial–Type 1 • IFG, impaired fasting glucose • IGT, impaired glucose tolerance • OGTT, oral glucose tolerance test

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