Adequate sleep duration accentuates the effect of glucagon-like peptide-1 receptor variant on HbA1c: A gene-environment interaction study

[Display omitted] Both glucagon-like peptide-1 receptor (GLP1R) agonists and lifestyle modifications are widely adopted in managing glycemia. However, the joint effects of GLP1R agonists with lifestyle on glycemic traits have not been evaluated. This gene-environment study tested the interaction between GLP1R-rs10305492 variant, consistent with the effect of GLP1R agonist therapies, and four lifestyle factors (diet, physical activity, sleep duration, and chronotype) for glucose and glycated hemoglobin (HbA1c) levels among 263,846 UK Biobank participants. Linear regression models were conducted to evaluate the effects of the rs10305492 and lifestyle factors on glucose and HbA1c levels. GLP1R-rs10305492-AA/AG genotype combined a healthy diet, regular physical activity, adequate sleep duration, or morning chronotype were associated with lower glucose and HbA1c levels (all P for trend 7.8 mmol/L) risk and a 22 % lower of high HbA1c (>39 mmol/mol or 5.7 %). Combining GLP1R agonists with adequate sleep may provide additional benefits for glycemic control in clinical practice.