February 18, 2021

Gene variant and glucose metabolism

Genetic variation that impacts glucose- and insulin-related signaling affects responses to type 2 diabetes treatments and warrants further study.

by Leigh MacMillan

GLP-1 (glucagon-like peptide-1) increases glucose-mediated insulin secretion. GLP-1 receptor agonists and DPP-4 inhibitors, which prevent GLP-1 inactivation, are widely used to treat type 2 diabetes mellitus. 

Mona Mashayekhi, MD, PhD, and colleagues explored whether a particular genetic variant in the GLP-1 receptor gene affected the metabolic response to a meal and to DPP-4 inhibition. They performed mixed meal studies in individuals with type 2 diabetes and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. 

The researchers report in Diabetes, Obesity and Metabolism that individuals with the GA/AA variant have decreased glucose excursion — spikes in blood sugar levels — and increased markers of insulin secretion after a meal compared to those with the GG variant. GG individuals, however, benefit most from the DPP-4 inhibitor. 

The findings support further study of the relationship between GLP-1 receptor genotype and therapies that modulate GLP-1 signaling, particularly as this class of agents becomes more broadly prescribed.

This research was supported by the National Institutes of Health (grants HL125426, DK007061, GM007569, TR001879, TR000445) and American Heart Association.