cardiovascular-agents and Prediabetic-State

To determine the comparative effectiveness of exercise versus drug interventions on mortality outcomes.. Metaepidemiological study.. Meta-analyses of randomised controlled trials with mortality outcomes comparing the effectiveness of exercise and drug interventions with each other or with control (placebo or usual care).. Medline and Cochrane Database of Systematic Reviews, May 2013.. Mortality.. We combined study level death outcomes from exercise and drug trials using random effects network meta-analysis.. We included 16 (four exercise and 12 drug) meta-analyses. Incorporating an additional three recent exercise trials, our review collectively included 305 randomised controlled trials with 339,274 participants. Across all four conditions with evidence on the effectiveness of exercise on mortality outcomes (secondary prevention of coronary heart disease, rehabilitation of stroke, treatment of heart failure, prevention of diabetes), 14,716 participants were randomised to physical activity interventions in 57 trials. No statistically detectable differences were evident between exercise and drug interventions in the secondary prevention of coronary heart disease and prediabetes. Physical activity interventions were more effective than drug treatment among patients with stroke (odds ratios, exercise v anticoagulants 0.09, 95% credible intervals 0.01 to 0.70 and exercise v antiplatelets 0.10, 0.01 to 0.62). Diuretics were more effective than exercise in heart failure (exercise v diuretics 4.11, 1.17 to 24.76). Inconsistency between direct and indirect comparisons was not significant.. Although limited in quantity, existing randomised trial evidence on exercise interventions suggests that exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.

Topics: Anticoagulants; Cardiovascular Agents; Comparative Effectiveness Research; Confounding Factors, Epidemiologic; Coronary Disease; Diuretics; Exercise Therapy; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Mortality; Odds Ratio; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Prediabetic State; Randomized Controlled Trials as Topic; Research Design; Stroke

Patients with diabetes and prediabetes are at high risk for micro- and macrovascular complications. A multifactorial management strategy improves their prognosis considerably. Of concern is that these patients often fall between two specialties: cardiovascular medicine and diabetology. Practice guidelines for this patient category have been issued in collaboration between the European Society of Cardiology and the European Association for the Study of Diabetes to ascertain management according to the best available evidence. This article discusses why and for whom such guidelines are important.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Practice Guidelines as Topic; Prediabetic State; Risk Reduction Behavior

The metabolic syndrome of vascular risk is threatening large numbers of ever-younger people. To date, the syndrome has been chiefly viewed as a potential risk marker that confers a heightened probability of developing type 2 diabetes and occlusive atherothrombotic disease of large- and medium-sized arteries. Accumulating evidence suggests that the components of the metabolic syndrome may also adversely affect the microvasculature through several inter-related mechanisms. These include the following observations: classic risk factors for macrovascular disease such as high blood pressure and dyslipidaemia also accelerate microvascular complications of diabetes, lesser disturbances of glucose metabolism (i.e. impaired glucose tolerance) may be associated with some forms of microvascular dysfunction, non-glucose intermediary metabolites may promote renovascular hypertension thereby damaging the microvasculature, and insulin resistance appears to be directly associated with microvascular dysfunction. In turn, microvascular complications such as nephropathy and autonomic neuropathy may promote the development and progression of atherosclerosis. We argue that the vascular implications of the metabolic syndrome should be broadened to include the microvasculature. The hypothesis that vascular events can be prevented, or at least deferred, through earlier therapeutic intervention in pre-diabetic subjects with glucose intolerance is amenable to testing in clinical trials.

Topics: Anti-Obesity Agents; Antihypertensive Agents; Atherosclerosis; Cardiovascular Agents; Disease Progression; Glucose Intolerance; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Metabolic Syndrome; Microcirculation; Prediabetic State; Risk Assessment; Risk Factors; Signal Transduction; Vascular Diseases

Topics: Cardiovascular Agents; Coronary Disease; Exercise Therapy; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Prediabetic State; Stroke

In the aorta of prediabetic non-obese diabetic mice, a model of human type 1 diabetes, we investigated gene expression of the endothelin receptors and contractility to big endothelin-1 and endothelin-1 at the ages of 10 and 16 weeks. A subgroup of 10- week-old animals was treated with the endothelin ETA receptor antagonist LU461314 (30 mg/kg per day for 6 weeks). Blood glucose levels were normal in all animals. Real-time polymerase chain reaction analysis revealed that vascular ETB receptor expression was higher in 10-week-old non-obese diabetic (NOD) mice compared with controls. In 16-week-old NOD mice, but not in control mice, ETB receptor mRNA was twofold lower (P < 0.05 vs 10-week-old NOD mice). In all groups ETA receptor expression was unaffected by age or treatment. Contractions to big endothelin-1 and endothelin-1 were lower in 10-week-old NOD mice compared with controls. Treatment with LU461314 increased ETB receptor expression in 16-week-old NOD mice, but had no effect on vascular contractility. These data indicate that dysregulation of ETB receptor expression and a decreased contractile response to big endothelin-1 and endothelin-1 are present in the prediabetic state of a model of human type 1 diabetes. These alterations occur independent of glucose levels. Furthermore, ETA receptor blockade is effective in increasing ETB receptor gene expression, suggesting a potential role for endothelin ETA antagonists in the treatment of type 1 diabetes.

Topics: Age Factors; Animals; Aorta; Blood Glucose; Cardiovascular Agents; Diabetes Mellitus, Type 1; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelin A Receptor Antagonists; Endothelin-1; Female; Mice; Mice, Inbred NOD; Prediabetic State; Receptor, Endothelin A; Receptor, Endothelin B; RNA, Messenger; Up-Regulation; Vasoconstriction