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Inappropriate glucagon and GLP-1 secretion in individuals with long-standing type 1 diabetes: effects of residual C-peptide

  • Charles ThivoletEmail author
  • Lucien Marchand
  • Karim Chikh
Article

Abstract

Aims/hypothesis

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).

Methods

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.

Results

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.

Conclusions/interpretation

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.

Keywords

Incretins Insulin microsecretion Pancreatic alpha cells Type 1 diabetes 

Abbreviations

GLP-1

Glucagon-like peptide-1

MMTT

Mixed meal tolerance test

Notes

Acknowledgements

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.

Contribution statement

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.

Funding

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Charles Thivolet
    • 1
    • 2
    Email author
  • Lucien Marchand
    • 1
    • 2
  • Karim Chikh
    • 2
    • 3
  1. 1.Department of Endocrinology and DiabetesLyon-Sud Hospital, Hospices Civils de LyonPierre-BéniteFrance
  2. 2.UnivLyon, Inserm, INRA, INSA Lyon, Université Claude Bernard Lyon 1OullinsFrance
  3. 3.Department of BiochemistryLyon-Sud Hospital, Hospices Civils de LyonPierre-BéniteFrance

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