Abstract 1621: Decreased Blood Levels of Active Glucagon-like Peptide 1 and Dipeptidyl Peptidase 4 Concentrations in Patients With Coronary Artery Disease
Background: Incretins, enhancers of insulin secretion, are gut-derived peptides secreted in response to meals and essential for glucose tolerance. The major incretins, glucagon-like peptide-1 (GLP-1), are decreased in patients with type-2 diabetes. Recently, GLP-1 analogue and an inhibitor of dipeptidyl peptidase 4 (DPP-4), a major degrading enzyme of GLP-1, are clinically used to treat type-2 diabetes. GLP-1 analogue has also demonstrated cardioprotective and vasodilatory actions, but the significance of basal blood levels of active GLP-1 and DPP-4 in cardiovascular diseases has not been well defined.
Methods and Results: Fasting plasma GLP-1(7–36) amide, the active form of GLP-1, and serum DPP-4 concentrations sampled from peripheral vein (PV) was measured by immunoassay in 55 consecutive high risk patients who were suspected of cardiovascular disease and free of antidiabetic drugs (73% men; 65 ± 11 years). Their hemoglobin A1c were 5.3 [5.1, 5.7] % for median [25th, 75th percentile] and 44% of them had coronary artery disease (CAD: n=24). Fasting active GLP-1 in PV was detectable (>2.0 pmol/L) in only 47% of the patients, and the levels were significantly reduced in CAD patients (0.0 [0.0, 2.3]) than non-CAD patients (2.4 [0.0, 4.3] pmol/L, p<0.05). Serum DPP-4 was detectable in all patients, and the levels were 474 [389, 551] ng/mL. DPP-4 was significantly reduced in men (444 [362, 522]) than women (540 [486, 635] ng/mL, p<0.05), in CAD patients (424 [362, 522]) than non-CAD patients (495 [429, 564] ng/mL, p<0.05). Serum DPP-4 was positively correlated with high density lipoprotein-cholesterol (ρ=0.43, p<0.01), and negatively correlated with left ventricular diameter (ρ= −0.35, p<0.05). DPP-4 and GLP-1 didn’t have significant correlation (ρ=0.25, p=0.17) with each other.
Conclusions: Fasting plasma levels of GLP-1 were low in high risk patients, and significantly reduced in CAD patients than non-CAD patients. Serum DPP-4 concentrations were significantly lower in men and CAD patients than the others, indicating possible association between incretins and pathogenesis of CAD. It would provide useful information to assess blood levels of GLP-1 and DPP-4 in association with cardiovascular diseases and its complication as incretin therapy prevails.