glucagon-like-peptide-1 and Coronary-Disease

Topics: Adaptation, Physiological; Adipose Tissue; Animals; Coronary Disease; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Obesity; Peptide Fragments

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

GLP-1 stimulates insulin secretion, suppresses glucagon secretion, delays gastric emptying, and inhibits small bowel motility, all actions contributing to the anti-diabetogenic peptide effect. Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus and may cause the angiopathy typifying this debilitating disease. Therefore, interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients. We investigated GLP-1's effect on endothelial function and insulin sensitivity (S(I)) in two groups: 1) 12 type 2 diabetes patients with stable coronary artery disease and 2) 10 healthy subjects with normal endothelial function and S(I). Subjects underwent infusion of recombinant GLP-1 or saline in a random crossover study. Endothelial function was measured by postischemic FMD of brachial artery, using ultrasonography. S(I) [in (10(-4) dl.kg(-1).min(-1))/(muU/ml)] was measured by hyperinsulinemic isoglycemic clamp technique. In type 2 diabetic subjects, GLP-1 infusion significantly increased relative changes in brachial artery diameter from baseline FMD(%) (3.1 +/- 0.6 vs. 6.6 +/- 1.0%, P < 0.05), with no significant effects on S(I) (4.5 +/- 0.8 vs. 5.2 +/- 0.9, P = NS). In healthy subjects, GLP-1 infusion affected neither FMD(%) (11.9 +/- 0.9 vs. 10.3 +/- 1.0%, P = NS) nor S(I) (14.8 +/- 1.8 vs. 11.6 +/- 2.0, P = NS). We conclude that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease. This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment.

Topics: Adult; Brachial Artery; Coronary Circulation; Coronary Disease; Coronary Vessels; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelial Cells; Endothelium, Vascular; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Insulin; Male; Middle Aged; Nitroglycerin; Peptide Fragments; Pilot Projects; Protein Precursors; Receptors, Glucagon; Regional Blood Flow; Vasodilation

Short-term studies suggest that extreme sucrose consumption has a detrimental effect on triglycerides (TG) in hypertriglyceridemic people. There is currently no consensus on the short-term inclusion of a moderate intake of sucrose in middle-aged men at increased risk of coronary heart disease (CHD). It is also unknown whether gut hormones that are released in response to carbohydrate ingestion modulate any of the effects of sucrose. The aim of this study was to further elucidate whether men at increased risk of CHD have an exaggerated response to sucrose compared with age- and weight-matched controls over an acute postprandial period. Twenty middle-aged men were recruited and separated into control (total cholesterol < 5.5 mmol/L) and increased risk of CHD (> 5.5 mmol/L) groups. We measured postprandial TG, nonesterified fatty acids (NEFA), insulin, glucose, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) concentrations in response to a meal containing 75 g glucose or 75 g sucrose with a moderate fat load. The increased risk group had significantly higher Framingham risk assessment (12% v 4%), TG (2.4 +/- 1.5 v 1.1 +/- 0.4 mmol/L), low-density lipoprotein-cholesterol (LDL-C) (4.4 +/- 0.5 v 2.7 +/- 0.4 mmol/L), and lower high-density lipoprotein-cholesterol (HDL-C) (1.2 +/- 0.2 v 1.5 +/- 0.2 mmol/L) (P <.05 for all). There was no significant difference in the incremental area under the curve (IAUC, 0 to 360 minutes) for TG, NEFA, glucose, GLP-1, or GIP in response to glucose or sucrose within or between the groups. Absolute total area under the curve (not IAUC) for TG was significantly higher in the increased risk group for both glucose and sucrose, respectively (P =.01). A total of 75 g of sucrose given as part of a single meal appears to make little difference in the postprandial TG and NEFA response in men with or without risk of CHD compared with glucose. Although long-term data is needed, this begs the question whether a moderate intake of sucrose has been overemphasized as a detrimental dietary message in middle-aged men.

Topics: Blood Glucose; Case-Control Studies; Coronary Disease; Fatty Acids, Nonesterified; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Male; Peptide Fragments; Postprandial Period; Risk Factors; Sucrose; Triglycerides

To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers.. Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score.. Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was ~60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF.. This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality.

Topics: Aged; Blood Glucose; Cardiotoxicity; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Heart Failure; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Registries; Sulfonylurea Compounds; Sweden; Thiazolidinediones; Treatment Outcome

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

Transoral gastroplasty (TOGA) is a safe and less invasive procedure than traditional bariatric surgery. We studied the effects of TOGA on the risk of progression from prediabetes to overt type 2 diabetes mellitus (T2DM) or on regression from diabetes or prediabetes to a lower risk category.. Prospective, observational study (October 2008 to October 2010) performed at Catholic University, Rome, Italy. Fifty consecutive subjects 18-60 years old, 35 ≥ body mass index < 55 kg/m², were enrolled. Glucose tolerance, insulin sensitivity, and secretion were studied at baseline and 1 week and 1, 6, and 12 months after TOGA. Plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and ghrelin levels were measured.. Forty-three patients (86%) completed the 1-year postoperative follow-up. Patients lost 16.90% of baseline weight (P level × factor time <0.001). Body mass index decreased from 42.24 ± 3.43 to 34.65 ± 4.58 kg/m² (P < .001). Twenty-three patients (53.5%) were diagnosed as normal glucose tolerance (NGT) before treatment, 2 (4.6%) were impaired fasting glucose (IFG), 12 (27.9%) were impaired glucose tolerance (IGT), 1 (2.3%) had both IFG and IGT, and 5 (11.6%) had T2DM. At 1-year posttreatment, the percentages changed to 86.0% NGT, 2.3% IFG, 11.6% IGT, 0% IFG plus IGT, and 0% T2DM, respectively. Peripheral insulin resistance and homeostasis model of assessment-insulin resistance improved significantly. Fasting glucose-dependent insulinotropic peptide and ghrelin decreased from 316.9 ± 143.1 to 156.2 ± 68.2 pg/mL (P < .001) and from 630.6 ± 52.1 to 456.7 ± 73.1 pg/mL (P < .001), respectively, whereas GLP-1 increased from 16.2 ± 4.9 to 23.7 ± 9.5 pg/mL (P < .001).. TOGA induced glucose disposal improvement with regression of diabetes to NGT or IGT and regression of IGT and IFG to NGT in half of the cases. Regressors showed a much larger increase of GLP-1 levels than progressors.

Topics: Adolescent; Adult; Body Mass Index; Coronary Disease; Diabetes Mellitus, Type 2; Disease Progression; Follow-Up Studies; Gastric Inhibitory Polypeptide; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Middle Aged; Obesity; Obesity, Morbid; Prediabetic State; Prospective Studies; Risk; Rome; Weight Loss; Young Adult

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.. 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 [DeltaGLP-1]) and CHD in a population-based 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.. 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. DeltaGLP-1 did not predict CHD (HR 1.0, 95% CI 0.52-2.28). The prevalence of IGT was associated with DeltaGLP-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 DeltaGLP-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.. 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 DeltaGLP-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.

Topics: Aged; Albuminuria; Blood Pressure; Cardiovascular Diseases; Cholesterol; Cohort Studies; Coronary Disease; Diabetes Mellitus, Type 2; Fasting; Follow-Up Studies; Glucagon-Like Peptide 1; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Male; Survival Analysis; Waist Circumference

Post-resuscitation syndrome leads to death in approximately 2 out of every 3 successfully resuscitated victims, and myocardial microcirculatory dysfunction is a major component of this syndrome. The aim of this study was to determine if glucagon-like peptide-1 (GLP-1) improves post-resuscitation myocardial microcirculatory function.. Ventricular fibrillation (VF) was induced electrically in 20 anesthetized domestic swine (30-35 kg). Following 8 min of untreated VF, animals were resuscitated with aggressive advanced cardiac life support (ACLS). Animals were blindly randomized to receive a continuous infusion of either GLP-1 (10 pM/kg/min) or equal volume saline as placebo (PBO) for 4h, beginning 1 min after return of spontaneous circulation (ROSC). Left ventricular (LV) haemodynamics, LV ejection fraction, cardiac output, and coronary flow reserve (CFR) [using a standard technique of intracoronary Doppler flow measurements before and after intracoronary administration of 60 microg adenosine] were performed pre-arrest and at 1 and 4h post-resuscitation. In the present study, CFR is a measure of myocardial microcirculatory function since these swine had no obstructive coronary artery disease. Twenty-four hour post-resuscitation survival and neurological functional scores were also determined.. CFR was significantly increased in GLP-1-treated animals, 1h (1.79+/-0.13 in control animals vs. 2.05+/-0.12 in GLP-1-treated animals, P = <0.05) and 4h (1.82+/-0.16 in control animals vs. 2.31+/-0.13 in GLP-1-treated animals, P = <0.05) after ROSC. In addition, compared to PBO-treated animals, GLP-1 increased cardiac output 1h after ROSC (2.1+/-0.1 in control animals vs. 2.7+/-0.2 in GLP-1-treated animals, P = <0.05). There was no statistically significant difference in survival between GLP-1-treated (100%) and PBO-treated animals (78%).. In this swine model of prolonged VF followed by successful resuscitation, myocardial microcirculatory function was enhanced with administration of GLP-1. However, GLP-1 treatment was not associated with a clinically significant improvement in post-resuscitation myocardial function.

Topics: Animals; Blood Glucose; Cardiac Output; Cardiopulmonary Resuscitation; Coronary Circulation; Coronary Disease; Glucagon-Like Peptide 1; Heart; Hemodynamics; Humans; Infusion Pumps; Insulin; Lactic Acid; Microcirculation; Nervous System; Osmolar Concentration; Survival Rate; Swine; Time Factors; Ventricular Fibrillation

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

Insulin resistance syndrome has recently been described as a unifying hypothesis to explain the relationship between the many risk factors of coronary heart disease. Carbohydrate that is malabsorbed and fermented in the colon has been demonstrated to decrease insulin response to a glucose load and improve other risk factors associated with coronary heart disease, although the mechanism remains unclear. The object of the present study was to investigate whether this observation could be explained by the production of fermentation products induced by malabsorbed carbohydrate in the colon, or by stimulating the incretin glucagon-like peptide 1 (7-36) amide that is released from the large bowel. We used lactulose as a model for resistant starch carbohydrate. Ten insulin-resistant male volunteers, who had undergone previous coronary artery bypass grafting, volunteered to take part in the study and underwent 6 d of lactulose loading (15 g/d for 2 d and 30 g/d for 4 d). There was no significant change in insulin, glucose, free fatty acids, or glucagon-like peptide 1 (7-36) amide response to an oral glucose tolerance test following the lactulose despite a significant rise in breath hydrogen. Large bowel fermentation stimulated by lactulose appears to have no significant effect on insulin, glucose, free fatty acids, and glucagon-like peptide 1 (7-36) response in patients with coronary heart disease.

Topics: Aged; Blood Glucose; Coronary Disease; Fatty Acids, Nonesterified; Fermentation; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Intestinal Absorption; Intestine, Large; Lactulose; Male; Middle Aged; Peptide Fragments; Risk Factors