Two- and Four-Hour Tests Differ in Capture of C-Peptide Responses to a Mixed Meal

Mixed-meal tolerance tests (MMTTs) are used in clinical trials to evaluate β-cell function in patients with new-onset type 1 diabetes (1,2). Some trials use a 4-h MMTT, whereas others use an abbreviated (2-h) protocol to reduce investigator and subject burden. In the T1DAL (Inducing Remission in Type 1 Diabetes With Alefacept) trial of patients with new-onset type 1 diabetes, the primary analysis using the 2-h test failed to reach statistical significance ( P = 0.065), but a 4-h test did ( P = 0.019) (3). We investigated the effect of abbreviating the test using data from 186 patients participating in three clinical trials conducted by the Immune Tolerance Network (3–5). Trials were approved by institutional review boards at the participating institutions. Written informed consent or assent was obtained.Each patient contributed up to three 4-h MMTTs, conducted yearly, for a total of 506 paired 2- and 4-h observations. For this analysis, the 4-h assessment, which captures more of the complete hormonal response, was selected as the reference. The percent of the total 4-h C-peptide area under the curve (AUC) captured in the first 2 h ranged from 28% to 72%. Mean AUCs (mAUCs) were computed as 2- or 4-h AUCs divided by duration, 120 or 240 min, respectively. The correlation between the 2- and 4-h mAUCs was 0.98. Generally, the variability of the 2-h test was greater than that of the 4-h test (Fig. 1 A ). After adjusting for baseline, however, the variability was similar.Figure 1 Analysis of 2- and 4-h C-peptide AUCs during MMTTs. The C-peptide …