Fall in C-peptide During First 2 Years From Diagnosis

Evidence of at Least Two Distinct Phases From Composite TrialNet Data

  1. on behalf of the Type 1 Diabetes TrialNet Study Group*
  1. 1Benaroya Research Institute, Seattle, Washington
  2. 2Department of Pediatrics, University of South Florida, Tampa, Florida
  3. 3Department of Pediatrics, University of California San Francisco, San Francisco, California
  4. 4Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver, Aurora, Colorado
  5. 5Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut
  6. 6Biostatistics Center, George Washington University, Washington, DC
  7. 7Veterans Affairs Puget Sound Health Care System and Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington
  8. 8Departments of Surgery and Microbiology and Immunology, Indiana University, Indianapolis, Indiana
  9. 9University of Miami Diabetes Research Institute, Miami, Florida
  1. Corresponding author: Carla J. Greenbaum, cjgreen{at}
  • †Deceased.


Interpretation of clinical trials to alter the decline in β-cell function after diagnosis of type 1 diabetes depends on a robust understanding of the natural history of disease. Combining data from Diabetes TrialNet studies, we describe the natural history of β-cell function from shortly after diagnosis through 2 years post study randomization, assess the degree of variability between patients, and investigate factors that may be related to C-peptide preservation or loss. We found that 93% of individuals have detectable C-peptide 2 years from diagnosis. In 11% of subjects, there was no significant fall from baseline by 2 years. There was a biphasic decline in C-peptide; the C-peptide slope was −0.0245 pmol/mL/month (95% CI −0.0271 to −0.0215) through the first 12 months and −0.0079 (−0.0113 to −0.0050) from 12 to 24 months (P < 0.001). This pattern of fall in C-peptide over time has implications for understanding trial results in which effects of therapy are most pronounced early and raises the possibility that there are time-dependent differences in pathophysiology. The robust data on the C-peptide obtained under clinical trial conditions should be used in planning and interpretation of clinical trials.

  • Received November 2, 2011.
  • Accepted March 9, 2012.

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