incretins and Coronary-Disease

This study sought to determine whether pre-treatment with intravenous glucagon-like peptide-1 (GLP-1)(7-36) amide could alter myocardial glucose use and protect the heart against ischemic left ventricular (LV) dysfunction during percutaneous coronary intervention.. GLP-1 has been shown to have favorable cardioprotective effects, but its mechanisms of action remain unclear.. Twenty patients with preserved LV function and single-vessel left anterior descending coronary artery disease undergoing elective percutaneous coronary intervention were studied. A conductance catheter was placed into the LV, and pressure-volume loops were recorded at baseline, during 1-min low-pressure balloon occlusion (BO), and at 30-min recovery. Patients were randomized to receive an infusion of either GLP-1(7-36) amide at 1.2 pmol/kg/min or saline immediately after baseline measurements. Simultaneous coronary artery and coronary sinus blood sampling was performed at baseline and after BO to assess transmyocardial glucose concentration gradients.. BO caused both ischemic LV dysfunction and stunning in the control group but not in the GLP-1 group. Compared with control subjects, the GLP-1 group had a smaller reduction in LV performance during BO (delta dP/dTmax, -4.3 vs. -19.0%, p = 0.02; delta stroke volume, -7.8 vs. -26.4%, p = 0.05), and improved LV performance at 30-min recovery. There was no difference in transmyocardial glucose concentration gradients between the 2 groups.. Pre-treatment with GLP-1(7-36) amide protects the heart against ischemic LV dysfunction and improves the recovery of function during reperfusion. This occurs without a detected change in myocardial glucose extraction and may indicate a mechanism of action independent of an effect on cardiac substrate use. (Effect of Glucgon-Like-Peptide-1 [GLP-1] on Left Ventricular Function During Percutaneous Coronary Intervention [PCI]; ISRCTN77442023).

Topics: Cardiac Catheterization; Coronary Disease; Female; Glucagon-Like Peptide 1; Humans; Incretins; Infusions, Intravenous; Male; Middle Aged; Myocardial Ischemia; Myocardial Stunning; Percutaneous Coronary Intervention; Treatment Outcome; Ventricular Dysfunction, Left

Post-prandial hyperglycemia, hyperlipidemia, and endothelial dysfunction play an important role in the pathogenesis of atherosclerosis. Improvement in post-prandial hyperglycemia on alpha-glucosidase inhibitors (alpha-GIs) is associated with a risk reduction of cardiovascular diseases, but the post-prandial effects of alpha-GIs on endothelial function and incretin secretion in type 2 diabetic patients with coronary artery disease (CAD) remain unclear.. The post-prandial effects of a single administration of miglitol and voglibose on endothelial function and changing levels of glucose, insulin, lipids, glucagon-like peptide (GLP)-1, and gastric inhibitory polypeptide (GIP) were compared after a standard meal loading in 11 diabetic patients with CAD, using a placebo-controlled cross-over design. The changing levels of glucose, insulin and triglycerides at 60 min were significantly lower in the miglitol group than in the voglibose and placebo groups (all P<0.01). GLP-1 levels were significantly higher at 120 min (P<0.05) and GIP levels were significantly lower at 30 min and 60 min (P<0.05) in the miglitol group compared to other treatments. The reactive hyperemia duration at 120 min was significantly maintained in the miglitol group compared to the other groups.. A single administration of miglitol significantly improved post-prandial glucose/lipid metabolism, incretin secretion, and endothelial dysfunction in diabetic patients with CAD, suggesting that miglitol may be a useful anti-atherogenic agent (UMIN000002264).

Topics: 1-Deoxynojirimycin; Aged; Coronary Artery Disease; Coronary Disease; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Endothelium, Vascular; Enzyme Inhibitors; Female; Glucose; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Incretins; Inositol; Lipid Metabolism; Male; Middle Aged; Treatment Outcome

Topics: Coronary Disease; Female; Glucagon-Like Peptide 1; Humans; Incretins; Male; Myocardial Ischemia; Myocardial Stunning; Percutaneous Coronary Intervention; Ventricular Dysfunction, Left

Topics: Aged; Blood Glucose; Coronary Disease; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Hemodynamics; Humans; Incretins; Injections, Intravenous; Male; Middle Aged; Postoperative Period; Treatment Outcome