Volume 61, Issue 8
C-Peptide--metabolism; Diabetes Mellitus; Type 1--physiopathology
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.
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Greenbaum, C. J., Beam, C. A., Boulware, D., Gitelman, S. E., Gottlieb, P. A., Herold, K. C., . . . Sosenko, J. M. (2012). Fall in C-peptide during first 2 years from diagnosis: Evidence of at least two distinct phases from composite type 1 diabetes trialnet data. Diabetes, 61(8), 2066-2073.