Reduced plasma levels of glucagon-like peptide-1 in elderly men are associated with impaired glucose tolerance but not with coronary heart disease

Abstract

Aims/hypothesis: Besides the insulinotropic effects of glucagon-like peptide-1 (GLP-1) mimetics, their effects on endothelial dysfunction and myocardial ischaemia are of interest. No previous study has investigated associations between plasma levels of GLP-1 and CHD. Methods: We investigated longitudinal relationships of fasting GLP-1 with the dynamic GLP-1 response after OGTT (difference between 60 min OGTT-stimulated and fasting GLP-1 levels [ΔGLP-1]) and CHD in a populationbased cohort of 71-year-old men. In the same cohort, we also cross-sectionally investigated the association between stimulated GLP-1 levels and: (1) cardiovascular risk factors (blood pressure, lipids, urinary albumin, waist circumference and insulin sensitivity index [M/I] assessed by euglycaemic-hyperinsulinaemic clamp); and (2) impaired glucose tolerance (IGT) and type 2 diabetes mellitus. Results: During the follow-up period (maximum 13.8 years), of 294 participants with normal glucose tolerance (NGT), 69 experienced a CHD event (13.8 years), as did 42 of 141 with IGT and 32 of 74 with type 2 diabetes mellitus. ΔGLP-1 did not predict CHD (HR 1.0, 95%CI 0.52-2.28). The prevalence of IGT was associated with ΔGLP-1, lowest vs highest quartile (OR 0.3, 95%CI 0.12-0.58), with no such association for type 2 diabetes mellitus (OR 1.0, 95% CI 0.38-2.86). M/I was significantly associated with ΔGLP-1 in the type 2 diabetes mellitus group (r=0.38, p<0.01), but not in the IGT (r=0.11, p=0.28) or NGT (r=0.10, p=0.16) groups. Conclusions/interpretation: Impaired GLP-1 secretion is associated with IGT, but not with type 2 diabetes mellitus. This finding in the latter group might be confounded by oral glucose-lowering treatment. GLP-1 does not predict CHD. Although ΔGLP-1 was associated with insulin sensitivity in the type 2 diabetes mellitus group GLP-1 does not seem to be a predictor of CHD in insulin-resistant patients.