Multiple factors regulate glucagon-like peptide-1 (GLP-1) secretion, but a group of apparently healthy subjects showed blunted responses of GLP-1 secretion in our previous study. In this study, we examined whether the reduction in GLP-1 secretory capacity is associated with increased extent of coronary artery stenosis in non-diabetic patients. Non-diabetic patients who were admitted for coronary angiography without a history of coronary interventions were enrolled. Coronary artery stenosis was quantified by Gensini score (GS), and GS ≥ 10 was used as an outcome variable based on its predictive value for cardiovascular events. The patients (mean age, 66.5 ± 8.8 years; 71% males, n = 173) underwent oral 75 g-glucose tolerant tests for determination of glucose, insulin and active GLP-1 levels. The area under the curve of plasma active GLP-1 (AUC-GLP-1) was determined as an index of GLP-1 secretory capacity. AUC-GLP-1 was not correlated with fasting glucose, AUC-glucose, serum lipids or indices of insulin sensitivity. In multivariate logistic regression analysis for GS ≥ 10, AUC-GLP-1 < median, age and hypertension were selected as explanatory variables, though fasting GLP-1 level was not selected. The findings suggest that reduction in GLP-1 secretory capacity is a novel independent risk factor of coronary stenosis.

Background and aim Glucagon-like peptide-1 (GLP-1) regulates insulin secretion and also affords pleiotropic effects including protective effects on blood vessels. Multiple factors regulate GLP-1 secretion after meals, but a group of apparently healthy subjects showed blunted responses of GLP-1 secretion in our previous study. In this study, we examined the possibility that the reduced capacity of GLP-1 secretion is associated with increased extent of coronary artery stenosis in non-diabetic patients. Methods and results Non-diabetic patients who were admitted for coronary angiography without a history of coronary interventions were enrolled. Coronary artery stenosis was quantified by Gensini score (GS), and GS ≥10 was used as an outcome variable based on results of earlier studies indicating its predictive value for cardiovascular events. The patients (mean age, 66.5±8.8 years; 71% males, n=173) underwent oral 75 g-glucose tolerant tests for determination of glucose, insulin and active GLP-1 levels. The area under the curve of plasma active GLP-1 (AUC-GLP-1) was determined as an index of GLP-1 secretion capacity. AUC-GLP-1 was not correlated with fasting glucose, AUC-glucose, serum lipids, indices of insulin sensitivity or estimated glomerular filtration rate. In multivariate logistic regression analysis for GS ≥10, AUC-GLP-1 &lt; median, age and hypertension were selected as explanatory variables, though fasting GLP-1 level was not selected. Conclusion The findings indicate significant association of reduced GLP-1 secretion capacity with increased extent of coronary artery stenosis in non-diabetic patients. A causal relationship between change in GLP-1 secretion capacity and coronary stenosis remains to be examined by a longitudinal study Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp./MSD K.K.