Abstract

Objective: Beta-cell function in type 1 diabetes (T1D) clinical trials is commonly measured by C-peptide response to a secretagogue in either a Mixed Meal Stimulation Test (MMTT) or a Glucagon Stimulation Test (GST). The Type 1 Diabetes TrialNet and the European C-peptide Trial (ECPT) Group conducted parallel randomized studies to compare the sensitivity, reproducibility and tolerability of these procedures.

Research Design and Methods: In randomized sequences, 148 TrialNet subjects completed 549 tests with up to two MMTT and two GST tests on separate days; and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs.

Results: Among individuals with up to 4 years duration of T1D, over 85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R²=0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age group.

Conclusions: The MMTT is preferred for the assessment of β-cell function in therapeutic trials in type 1 diabetes.