This article is more than 5 years old. Information may no longer be current.
C-peptide stimulation method may influence long-term type 1 diabetes treatment
In intervention trials, the calculation of long-term changes in stimulated C-peptide, which serves as an indicator of native insulin secretion in patients with type 1 diabetes, appears to be influenced by the method of C-peptide stimulation used, according to recent study findings.
Researchers compiled data from two clinical trials, DIA-AID 1 and the LADA study. DIA-AID 1 is a phase 3, double blind, placebo-controlled, parallel-group study evaluating the safety and efficacy of DiaPep277 (Andromeda Biotech) as an ancillary treatment in patients with newly diagnosed type 1 diabetes on an insulin treatment regimen. The LADA study was a phase 2, randomized, double blind, placebo-controlled, parallel-group clinical trial that also evaluated the safety and tolerability of DiaPep277.
In both of these studies, changes in stimulated C-peptide secretion, which serves as an approximation of endogenous insulin secretion, were measured as C-peptide area under the curve. Two common C-peptide stimulation methods, the glucagon stimulation test (GST) and the mixed-meal tolerance test (MMTT), were used.
In the DIA-AID 1 study, the change in stimulated C-peptide secretion was gauged from baseline to study completion at month 24. Measurement of this change evaluated by GST was the study’s primary endpoint, whereas measurement with MMTT was defined as the secondary endpoint.
Data culled from the DIA-AID study showed significantly maintained C-peptide secretion in the DiaPep277 treatment arm vs. placebo when measured by GST, but not by MMTT. The current study utilized data for all patients from the DIA-AID and the LADA studies (n=343) for whom GST and MMTT data were available at baseline and studies’ end. The researchers utilized Pearson’s correlations to calculate absolute AUC peptide at baseline, 12 and 24 months, and for long-term changes in AUC.
The researchers found that between both data groups, there was a strong correlation between the two tests in absolute AUC noted at any single time point (r= 0.74-0.9). However, significantly weaker correlations were found in measurements of AUC change (r=0.39-0.58). Although C-peptide secretion stimulated by GST remained steady over the fasting glucose range allowed for the test (4 mmol/L to 11.1 mmol/L), MMTT-stimulated C-peptide secretion decreased over that range. This finding suggested the possibility that MMTT was affected by the “incretin effect,” in which gastrointestinal mechanisms may be influenced by an oral nutrient delivery.
Because of this disparity in long-term AUCs, both methods of stimulation should be used in testing patients with newly diagnosed type 1 diabetes, the researchers said.
“This discrepancy is of particular importance, since it is long-term AUCs, rather than absolute AUCs, that indicate change from baseline and thus reveal the dynamics of disease progression,” the researchers wrote.
Disclosure: Pozzilli and two other researchers are consultants to Andromeda Biotech. Six of the researchers are employees of Andromeda Biotech, and two are the inventors of DiaPep277.