Trends of Earlier and Later Responses of C-peptide to Oral Glucose Challenges with Progression to Type 1 Diabetes in Diabetes Prevention Trial-Type 1 Participants Running Title: C-peptide with Progression to Type 1 Diabetes
- Jay M. Sosenko, MD (jsosenko{at}med.miami.edu)(1),
- Jerry P. Palmer, MD(2),
- Lisa E. Rafkin-Mervis, MS, CDE(1),
- Jeffrey P. Krischer, PhD(3),
- David Cuthbertson, MS(4),
- Carla J. Greenbaum, MD(5),
- George Eisenbarth, MD, PhD(6),
- Jay S. Skyler, MD(1) and
- the Diabetes Prevention Trial-1 Study Group
- 1. Division of Endocrinology, University of Miami, PO Box 016960 (D110), Miami, FL 33101
- 2. Division of Endocrinology/Metabolism, University of Washington, Seattle, WA
- 3. Division of Informatics and Biostatistics, University of South, Florida, Tampa, FL
- 4. Pediatrics Epidemiology Center, University of South Florida, Tampa, FL
- 5. Benaroya Research Institute at Virginia Mason, Seattle, WA
- 6. HLA/DNA Laboratory, University of Colorado, Aurora, CO
Abstract
Objective. We studied the C-peptide response to oral glucose with progression to type 1 diabetes (T1D) in Diabetes Prevention Trial-Type 1 (DPT-1) participants.
Methods. Among 504 DPT-1 participants <15 years of age, longitudinal analyses were performed in 36 progressors and 80 non-progressors. Progressors had oral glucose tolerance tests (OGTTs) at baseline and every 6 months from 2.0 years to 0.5 years before diagnosis; non-progressors had OGTTs over similar intervals prior to their last visit. Sixty-six progressors and 192 non-progressors were also studied proximal to and at diagnosis.
Results. The 30-0 minute C-peptide difference from OGTTs performed 2.0 years before diagnosis in progressors was lower than the 30-0 minute C-peptide difference from OGTTs performed 2.0 years before the last visit in non-progressors (p<0.01), and remained lower over time. The 90-60 minute C-peptide difference increased at every OGTT before diagnosis in progressors, whereas it declined at every OGTT before the last visit in non-progressors (p<0.01 at 2.0 years). The percentage whose peak C-peptide occurred at 120 minutes was higher in progressors at 2.0 years (p<0.05); this persisted over time (p<0.001 at 0.5 years). However, the peak C-peptide levels were only significantly lower at 0.5 years in progressors (p<0.01). The timing of the peak C-peptide predicted T1D (p<0.001); peak C-peptide levels were less predictive (p<0.05).
Conclusion. A decreased early C-peptide response to oral glucose and an increased later response occur at least two years before the diagnosis of T1D.
Footnotes
-
- Received September 22, 2009.
- Accepted December 10, 2009.
- Copyright © American Diabetes Association
