Fasting C-Peptide Level Determines Residual Beta-Cell Function

Stockholm—A multinational, placebo-controlled phase 3 study found that a fasting C-peptide level >0.1 nmol/L could reasonably determine residual beta-cell function in patients with new-onset type 1 diabetes mellitus (T1DM). In addition, a fasting C-peptide level >0.1 nmol/L combined with a 120-minute postmeal sample for subjects who fell below the threshold captured 99% of subjects compared with a full mixed-meal tolerance test (MMTT). The results were presented during a poster session at the EASD meeting. In this study, the researchers used baseline data on fasting C-peptide levels in subjects with new-onset T1DM from the DEFEND-1 (Durable-Response Therapy Evaluation for Early or New-Onset Type 1 Diabetes) trial. DEFEND-1 studied the safety and efficacy of otelixizumab, an investigational Fc-disabled anti-CD3 monoclonal antibody with T-cell immunomodulatory activity. They wanted to determine the optimal single time point postmeal for determining maximum C-peptide in adults and adolescents with new-onset T1DM. Researchers typically use stimulated C-peptide to determine residual beta-cell function. The study participants were 12 to 45 years of age, enrolled within 90 days of new-onset T1DM diagnosis, had at least 1 T1DM-associated autoantibody, and were otherwise healthy. Adult subjects had an MMTT at screening and another MMTT at predose, which occurred ≤14 days before the first dose of the study drug. Subjects <18 years of age had a C-peptide assessment at 120 minutes postmeal at screening and a full MMTT at predose. The eligibility criteria stipulated that subjects had to have a maximum stimulated C-peptide level >0.20 nmol/L at screening or predose. The authors examined data from 243 adult and 29 adolescent subjects who received otelixizumab or placebo, as well as 101 adults and 8 adolescents who failed screening. There were also values available for fasting and stimulated C-peptide for 339 patients. The researchers found a high correlation between fasting C-peptide and maximum stimulated C-peptide (r=.76; P<.0001). The age group of the subjects had no significant effect on the correlation. In addition, a fasting C-peptide level >0.1 nmol/L in adults had a sensitivity of 88% and a specificity of 75% to identify subjects with a maximum stimulated C-peptide level >0.2 nmol/L. The same cutoff value in adolescents had a sensitivity of 78% to identify subjects with a maximum stimulated C-peptide level >0.2 nmol/L. The authors could not determine specificity because no adolescents had a maximum stimulated C-peptide level <0.2 nmol/L. In 42% of the subjects, maximum stimulated C-peptide occurred at 120 minutes. Maximum values occurred at 30, 60, and 90 minutes in 5%, 16%, and 35% of subjects, respectively. There were 334 subjects with a recorded C-peptide level at 120 minutes, and 326 of the 334 subjects had a maximum stimulated C-peptide level >0.2 nmol/L. Of those 326, only 2 (0.6%) had a C-peptide level <0.2 nmol/L at 120 minutes.—Tim Casey