Inappropriate glucagon and GLP-1 secretion in individuals with long-standing type 1 diabetes: effects of residual C-peptide
Recent studies have demonstrated that residual beta cells may be present in some people with long-standing type 1 diabetes, but little is known about the potential impact of this finding on alpha cell function and incretin levels. This study aimed to evaluate whether insulin microsecretion could modulate glucagon and glucagon-like peptide-1 (GLP-1) responses to a mixed meal tolerance test (MMTT).
Adults with type 1 diabetes onset after the age of 15 years (n = 29) underwent a liquid MMTT after an overnight fast. Insulin microsecretion was defined when peak C-peptide levels were >30 pmol/l using an ultrasensitive assay. Four individuals with recent-onset type 1 diabetes were included as controls. Glucagon and GLP-1 responses were analysed according to C-peptide patterns.
We found comparable peak values, Δ0–max levels and AUCs of glucagon and GLP-1 responses in C-peptide-positive participants (n = 9) and C-peptide-negative participants (n = 16) with long-standing diabetes and in participants with recent-onset diabetes (n = 4). Mean glucagon levels, however, differed (p = 0.01). Mean GLP-1 responses were significantly lower according to C-peptide positivity (p < 0.001, ANOVA). Interestingly, GLP-1 levels correlated to glucagon values in C-peptide-positive participants with long-standing diabetes (Pearson’s r = 0.915, p = 0.004) and in participants with recent-onset diabetes (p < 0.001) but not in C-peptide-negative participants.
The glucagon response to an MMTT in people with long-standing type 1 diabetes is not reduced by the presence of residual beta cells. The reduction of GLP-1 responses according to residual C-peptide levels suggests specific regulatory pathways.
KeywordsIncretins Insulin microsecretion Pancreatic alpha cells Type 1 diabetes
Mixed meal tolerance test
We are indebted to S. Reffet, M. Buchy and L. Kepenekian from the Department of Endocrinology and Diabetes, Lyon-Sud Hospital for their help with selecting study participants.
CT and LM contributed to the original research idea. KC carried out the hormonal evaluations. CT was responsible for the statistical analysis and as such is the guarantor of this work and takes responsibility for the integrity of the data. All authors wrote, revised and edited the manuscript, had full access to the data, and read and approved the final version of the manuscript.
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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