Fall in C-Peptide During First 2 Years From Diagnosis
Evidence of at Least Two Distinct Phases From Composite Type 1 Diabetes TrialNet Data
- Carla J. Greenbaum1⇓,
- Craig A. Beam2,
- David Boulware2,
- Stephen E. Gitelman3,
- Peter A. Gottlieb4,
- Kevan C. Herold5,
- John M. Lachin6,
- Paula McGee6,
- Jerry P. Palmer7,
- Mark D. Pescovitz8,†,
- Heidi Krause-Steinrauf6,
- Jay S. Skyler9,
- Jay M. Sosenko9 and
- on behalf of the Type 1 Diabetes TrialNet Study Group*
- 1Benaroya Research Institute, Seattle, Washington
- 2Department of Pediatrics, University of South Florida, Tampa, Florida
- 3Department of Pediatrics, University of California San Francisco, San Francisco, California
- 4Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver, Aurora, Colorado
- 5Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut
- 6Biostatistics Center, George Washington University, Washington, DC
- 7Veterans Affairs Puget Sound Health Care System and Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington
- 8Departments of Surgery and Microbiology and Immunology, Indiana University, Indianapolis, Indiana
- 9University of Miami Diabetes Research Institute, Miami, Florida
- Corresponding author: Carla J. Greenbaum, .
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 the Type 1 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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1538/-/DC1.
* A complete list of the Type 1 Diabetes TrialNet Study Group can be found in the Supplementary Data online.
- Received November 2, 2011.
- Accepted March 9, 2012.
- © 2012 by the American Diabetes Association.
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