Fall in C-Peptide During First 2 Years From Diagnosis: Evidence of at Least Two Distinct Phases From Composite Type 1 Diabetes TrialNet Data

Benaroya Research Institute, Seattle, Washington, USA.
Diabetes (Impact Factor: 8.1). 06/2012; 61(8):2066-73. DOI: 10.2337/db11-1538
Source: PubMed


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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Available from: Paula Mcgee, Feb 16, 2015
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    • "Importantly, evidence for significant dysfunction of pancreatic beta cells is emerging from unpublished data from the new onset patients in the DiVid study [52] and from our own pancreas transplant recipients with disease recurrence, in which impaired beta cell function is shown despite the presence of insulin-positive cells at biopsy. These findings concur with recent reports showing that C-peptide secretion can persist in many patients, albeit at low levels, for several years after diagnosis [28•, 67•, 68•]. Altogether, these findings suggest the hypothesis that some patients might perhaps benefit from therapy to alter disease course or promote beta cell regeneration beyond just a few months after diagnosis; there is now a trend towards conducting clinical trials in patients with longer disease duration which will inform us as to whether there is indeed a wider window of therapeutic opportunity. "
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