Glucose Excursions Between States of Glycemia With Progression to Type 1 Diabetes in the Diabetes Prevention Trial–Type 1 (DPT-1)
- Jay M. Sosenko1,
- Jay S. Skyler1,
- Jeffrey P. Krischer2,
- Carla J. Greenbaum3,
- Jeffrey Mahon4,
- Lisa E. Rafkin1,
- David Cuthbertson5,
- Catherine Cowie6,
- Kevan Herold7,
- George Eisenbarth8,
- Jerry P. Palmer9 and
- the Diabetes Prevention Trial–Type 1 Study Group
- 1Division of Endocrinology, University of Miami, Miami, Florida;
- 2Division of Informatics and Biostatistics, University of South Florida, Tampa, Florida;
- 3Benaroya Research Institute at Virginia Mason, Seattle, Washington;
- 4Department of Epidemiology and Biostatistics, University of Western Ontario, Ontario, Canada;
- 5Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida;
- 6National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
- 7Yale University School of Medicine, New Haven, Connecticut;
- 8HLA/DNA Laboratory, University of Colorado, Aurora, Colorado;
- 9Division of Endocrinology, Metabolism, and Nutrition, Veterans Administration Puget Sound Health Care System, University of Washington, Seattle, Washington.
- Corresponding author: Jay M. Sosenko, .
OBJECTIVE We characterized fluctuations between states of glycemia in progressors to type 1 diabetes and studied whether those fluctuations are related to the early C-peptide response to oral glucose.
RESEARCH DESIGN AND METHODS Oral glucose tolerance tests (OGTTs) from differing states of glycemia were compared within individuals for glucose and C-peptide. Dysglycemic OGTTs (DYSOGTTs) were compared with normal OGTTs (NLOGTT), while transient diabetic OGTTs (TDOGTTs) were compared with subsequent nondiabetic OGTTs and with OGTTs performed at diagnosis.
RESULTS Of 135 progressors with four or more OGTTs, 30 (22%) went from NLOGTTs to DYSOGTTs at least twice. Area under the curve (AUC) glucose values from the second NLOGTT were higher (P < 0.001) than values from the first NLOGTT. Among 98 progressors whose DYSOGTTs and NLOGTTs were synchronized for the time before diagnosis, despite higher glucose levels (P < 0.01 at all time points) in the DYSOGTTs, 30- to 0-min C-peptide difference values changed little. Likewise, 30- to 0-min C-peptide difference values did not differ between TDOGTTs and subsequent (within 3 months) nondiabetic OGTTs in 55 progressors. In contrast, as glucose levels increased overall from the first to last OGTTs before diagnosis (P < 0.001 at every time point, n = 207), 30- to 0-min C-peptide difference values decreased (P < 0.001).
CONCLUSIONS Glucose levels fluctuate widely as they gradually increase overall with progression to type 1 diabetes. As glucose levels increase, the early C-peptide response declines. In contrast, glucose fluctuations are not related to the early C-peptide response. This suggests that changes in insulin sensitivity underlie the glucose fluctuations.
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- Received April 15, 2010.
- Accepted July 19, 2010.
- © 2010 by the American Diabetes Association.
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