Effect of GLP-1 and GIP on C-peptide secretion after glucagon or mixed meal tests: Significance in assessing B-cell function in diabetes

BACKGROUND:The aim of the study was to investigate the different B-cell responses after a glucagon stimulation test (GST) versus mixed meal tolerance test (MMTT).METHODS:We conducted GST and MMTT in 10 healthy people (aged 25-40 years) and measured C-peptide, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) at different time points after the administration of 1 mg i.v. glucagon for GST or a liquid mixed meal for MMTT.RESULTS:The GST stimulated C-peptide showed a mean increase of 147.1%, whereas the mean increase of MMTT stimulated C-peptide was 99.82% (Δincrease = 47.2%). Maximum C-peptide level reached with the MMTT was greater than that obtained with the GST (C-pept max MMTT = 2.35 nmol/L vs C-pep max GST = 1.9 nmol/L). A positive and linear correlation was found between the GST incremental area under the curve C-peptide and the MMTT incremental area under the curve C-peptide (r = 0.618, P = .05). After GST, there was no increment of GIP and glucagon like peptide-1 levels compared to baseline levels. A positive and linear correlation between GIP and C-peptide levels was observed only for the MMTT (r = 0.922, P = .008) indicating that in the GST, the C-peptide response is independent of the incretin axis response.CONCLUSIONS:Although the 2 stimulation tests may elicit a similar response in C-peptide secretion, B-cell response to MMTT depends on a functionally normal incretin axis. These results may have implications when investigating the B-cell response in people with diabetes and for studies in which stimulated C-peptide secretion is used as primary or secondary outcome for response to therapy.