Fall in C-Peptide During First 2 Years From Diagnosis
Open Access
- 17 July 2012
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 61 (8), 2066-2073
- https://doi.org/10.2337/db11-1538
Abstract
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.Keywords
This publication has 34 references indexed in Scilit:
- Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trialThe Lancet, 2011
- Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trialThe Lancet, 2011
- Metabolic tests to determine risk for type 1 diabetes in clinical trialsDiabetes/Metabolism Research and Reviews, 2011
- Residual Insulin Production and Pancreatic β-Cell Turnover After 50 Years of Diabetes: Joslin Medalist StudyDiabetes, 2010
- Failure to Preserve β-Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New- Onset Type 1 DiabetesDiabetes Care, 2010
- C‐peptide in the natural history of type 1 diabetesDiabetes/Metabolism Research and Reviews, 2009
- Glucose and C-Peptide Changes in the Perionset Period of Type 1 Diabetes in the Diabetes Prevention Trial–Type 1Diabetes Care, 2008
- Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 DiabetesDiabetes Care, 2008
- The Rising Incidence of Type 1 Diabetes Is Accounted for by Cases With Lower-Risk Human Leukocyte Antigen GenotypesDiabetes Care, 2008
- Estimating regression models with unknown break‐pointsStatistics in Medicine, 2003