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

  1. Jay M. Sosenko, MD (jsosenko{at}med.miami.edu)(1),
  2. Jerry P. Palmer, MD(2),
  3. Lisa E. Rafkin-Mervis, MS, CDE(1),
  4. Jeffrey P. Krischer, PhD(3),
  5. David Cuthbertson, MS(4),
  6. Carla J. Greenbaum, MD(5),
  7. George Eisenbarth, MD, PhD(6),
  8. Jay S. Skyler, MD(1) and
  9. the Diabetes Prevention Trial-1 Study Group
  1. 1. Division of Endocrinology, University of Miami, PO Box 016960 (D110), Miami, FL 33101
  2. 2. Division of Endocrinology/Metabolism, University of Washington, Seattle, WA
  3. 3. Division of Informatics and Biostatistics, University of South, Florida, Tampa, FL
  4. 4. Pediatrics Epidemiology Center, University of South Florida, Tampa, FL
  5. 5. Benaroya Research Institute at Virginia Mason, Seattle, WA
  6. 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.

This Article

  1. Diabetes Care
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