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

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 8; pp. 2066 - 2073
• Main Authors: GREENBAUM, Carla J, BEAM, Craig A, KRAUSE-STEINRAUF, Heidi, SKYLER, Jay S, SOSENKO, Jay M, BOULWARE, David, GITELMAN, Stephen E, GOTTLIEB, Peter A, HEROLD, Kevan C, LACHIN, John M, MCGEE, Paula, PALMER, Jerry P, PESCOVITZ, Mark D
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2012
• Subjects: Adolescent; Adult; Biological and medical sciences; C-Peptide - metabolism; Care and treatment; Child; Clinical trials; Diabetes; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Diagnosis; Disease; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic aspects; Glucose Tolerance Test; Health aspects; Humans; Insulin - therapeutic use; Insulin-Secreting Cells - physiology; Measurement; Medical sciences; Middle Aged; Pathophysiology; Peptides; Randomized Controlled Trials as Topic; Type 1 diabetes; United States; Endocrinopathy; Immunopathology; Autoimmune disease; Diagnosis; Type 1 diabetes; C-Peptide
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db11-1538

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.