Association of a glucagon-like peptide-1 receptor gene variant with glucose response to a mixed meal.

Citation
Mashayekhi, M., et al. “Association Of A Glucagon-Like Peptide-1 Receptor Gene Variant With Glucose Response To A Mixed Meal.”. Diabetes, Obesity & Metabolism, pp. 281-286.
Center Vanderbilt University
Author Mona Mashayekhi, Jessica R Wilson, Scott Jafarian-Kerman, Hui Nian, Chang Yu, Megan M Shuey, James M Luther, Nancy J Brown
Keywords DPP-4, GLP-1, GLP1R, dipeptidyl peptidase-4, glucagon-like peptide 1, sitagliptin
Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous glucagon-like peptide-1 (GLP-1). We hypothesized that genetic variation in the gene encoding the GLP-1 receptor (GLP1R) could affect the metabolic response to DPP-4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G-to-A nucleic acid substitution) and metabolic responses, we performed mixed meal studies in individuals with type 2 diabetes mellitus and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. This analysis is a substudy of NCT02130687. The genotype frequency was 13:12:7 GG:GA:AA among individuals of European ancestry. Postprandial glucose excursion was significantly decreased in individuals carrying the rs6923761 variant (GA or AA) as compared with GG individuals during both placebo (P = 0.001) and sitagliptin treatment (P = 0.045), while intact GLP-1 levels were similar among the genotype groups. In contrast, sitagliptin lowered postprandial glucose to a greater degree in GG as compared with GA/AA individuals (P = 0.035). The relationship between GLP1R rs6923761 genotype and therapies that modulate GLP-1 signalling merits study in large populations.

Year of Publication
2021
Journal
Diabetes, obesity & metabolism
Volume
23
Issue
1
Number of Pages
281-286
Date Published
01/2021
ISSN Number
1463-1326
DOI
10.1111/dom.14216
Alternate Journal
Diabetes Obes Metab
PMID
33001556