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Association of a glucagon‐like peptide‐1 receptor gene variant with glucose response to a mixed meal
Author(s) -
Mashayekhi Mona,
Wilson Jessica R.,
JafarianKerman Scott,
Nian Hui,
Yu Chang,
Shuey Megan M.,
Luther James M.,
Brown Nancy J.
Publication year - 2021
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14216
Subject(s) - meal , association (psychology) , glucagon like peptide 1 , glucagon like peptide 1 receptor , medicine , glucagon , endocrinology , gene , chemistry , receptor , biochemistry , diabetes mellitus , psychology , insulin , type 2 diabetes , agonist , psychotherapist
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.