glucagon-like-peptide-1 and Acute-Coronary-Syndrome

Type 2 diabetes and acute coronary syndromes (ACS) are widely interconnected. Individuals with type 2 diabetes are more likely than non-diabetic subjects to experience silent or manifest episodes of myocardial ischaemia as the first presentation of coronary artery disease. Insulin resistance, inflammation, microvascular disease, and a tendency to thrombosis are common in these patients. Intensive blood glucose control with intravenous insulin infusion has been demonstrated to significantly reduce morbidity and mortality in critically ill hyperglycaemic patients admitted to an intensive care unit (ICU). Direct glucose toxicity likely plays a crucial role in explaining the clinical benefits of intensive insulin therapy in such critical patients. However, the difficult implementation of nurse-driven protocols for insulin infusion able to lead to rapid and effective blood glucose control without significant episodes of hypoglycaemia has led to poor implementations of insulin infusion protocols in coronary care units, and cardiologists now to consider alternative drugs for this purpose. New intravenous or oral agents include the incretin glucagon-like peptide 1 (GLP1), its analogues, and dipeptidyl peptidase-4 inhibitors, which potentiate the activity of GLP1 and thus enhance glucose-dependent insulin secretion. Improved glycaemic control with protective effects on myocardial and vascular tissues, with lesser side effects and a better therapeutic compliance, may represent an important therapeutic potential for this class of drugs in acutely ill patients in general and patients with ACS in particular. Such drugs should be known by practicing cardiologists for their possible use in ICUs in the years to come.

Topics: Acute Coronary Syndrome; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Incretins; Prognosis

The relationship between plasma glucagon-like peptide-1 (GLP-1) and coronary plaque characteristics in humans remains unclear.. A total of 85 culprit coronary vessels excluding the 10-mm culprit segments in non-diabetic patients with acute coronary syndrome (ACS) were examined using integrated backscatter intravascular ultrasound, performed using a 40-MHz intravascular catheter before PCI. All patients underwent 75-g oral glucose tolerance test (OGTT), and the plasma GLP-1 response was evaluated on the basis of the area under the GLP-1 concentration-time curve (GLP-1 AUC) from 0 to 120 min. Patients in the low GLP-1 AUC tertile had a significantly greater percentage lipid area than did patients in the intermediate and high tertiles (low tertile vs. intermediate tertile vs. high tertile: 57.3 ± 12.1% vs. 47.2 ± 15.4% vs. 46.3 ± 12.7%, P<0.01, ANOVA) and a smaller percentage fibrosis area (38.1 ± 9.4% vs. 44.6 ± 11.5% vs. 45.7 ± 9.0%; P=0.01, ANOVA). On multiple regression analysis, low GLP-1 AUC tertile was independently associated with percentage lipid area.. Low plasma GLP-1 during 75-g OGTT is associated with increased lipid content in non-diabetic patients with ACS, suggesting that plaque vulnerability is increased in this subgroup of patients.

Topics: Acute Coronary Syndrome; Aged; Coronary Artery Disease; Diabetes Mellitus; Female; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Plaque, Atherosclerotic; Ultrasonography, Interventional

Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated.. ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy.. Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events.. ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Diseases; Double-Blind Method; Female; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; p38 Mitogen-Activated Protein Kinases; Peptides; Placebos; Protein Kinase Inhibitors; Research Design

Newly detected impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM) are common in patients with acute coronary syndrome (ACS; i.e. unstable angina/myocardial infarction) and related to disturbed beta-cell function. The aim of this study is to test the hypothesis that treatment with a dipeptidyl peptidase-4 inhibitor initiated soon after a coronary event improves beta-cell function.. Acute coronary syndrome ACS patients with IGT or T2DM (n = 71), screened by oral glucose tolerance test (OGTT) 4-23 days (median 6 days) after hospital admission, were randomly assigned to sitagliptin 100 mg (n = 34) or placebo (n = 37) and treated for a duration of 12 weeks. All patients received lifestyle advice but no glucose-lowering agents other than the study drug. The study end-point was beta-cell function assessed using the insulinogenic index (IGI = ΔInsulin30 /ΔGlucose30 ), derived from an OGTT, and acute insulin response to glucose (AIRg) assessed by a frequently sampled intravenous glucose tolerance test.. The IGI and AIRg did not differ at baseline between the sitagliptin and placebo groups (69.9 vs. 66.4 pmol mmol(-1) and 1394 vs. 1106 pmol L(-1) min(-1) respectively). After 12 weeks, the IGI was 85.0 in the sitagliptin and 58.1 pmol/mmol in the placebo group (P = 0.013) and AIRg was 1909 and 1043 pmol L(-1) min(-1) (P < 0.0001) in the sitagliptin and placebo groups respectively. Fasting glucose at baseline was 6.1 mmol L(-1) in sitagliptin-treated patients and 6.0 mmol L(-1) in those who received placebo compared with 5.8 and 5.9 mmol L(-1) respectively, after 12 weeks of treatment. Post load glucose metabolism improved in significantly more sitagliptin-treated patients compared with the placebo group (P = 0.003). Sitagliptin was well tolerated.. Sitagliptin improved beta-cell function and glucose perturbations in patients with ACS and newly diagnosed glucose disturbances.

Topics: Acute Coronary Syndrome; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Follow-Up Studies; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin-Secreting Cells; Prospective Studies; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles