Heart failure in diabetic patients: utility of beta-blockade
BACKGROUND: Congestive heart failure (CHF) occurs with increased frequency in patients with diabetes and carries a higher risk of morbidity and mortality compared with nondiabetic persons. Diabetic patients are more likely to suffer from CHF and its consequences because of hypertensive and ischemic heart disease and diabetic cardiomyopathy. METHODS: Intensive combination therapy, directed at the different aspects of the pathophysiology of CHF in diabetes patients, results in improved outcomes. Improvement of glycemia, reduction of low-density lipoprotein cholesterol levels, tight control of blood pressure, and antiplatelet therapy have been all shown to decrease the morbidity and mortality associated with CHF in diabetic patients. beta-blockade added to angiotensin-converting enzyme (ACE) inhibition has become an increasingly integral component of CHF therapy. RESULTS: Improved outcome with beta-blockade treatment is due to decreased incidence of both sudden death and pump failure and is of particular benefit to diabetic patients during and after myocardial infarctions complicated by systolic dysfunction. CONCLUSIONS: Based on retrospective analysis, beta-blocking agents with vasodilating properties may provide additional benefits in diabetic patients because they may improve insulin sensitivity and vasorelaxation.
Metformin: an update
Metformin is an insulin-sensitizing agent with potent antihyperglycemic properties. Its efficacy in reducing hyperglycemia in type 2 diabetes mellitus is similar to that of sulfonylureas, thiazolidinediones, and insulin. Metformin-based combination therapy is often superior to therapy with a single hypoglycemic agent. The antihyperglycemic properties of metformin are mainly attributed to suppressed hepatic glucose production, especially hepatic gluconeogenesis, and increased peripheral tissue insulin sensitivity. Although the precise mechanism of hypoglycemic action of metformin remains unclear, it probably interrupts mitochondrial oxidative processes in the liver and corrects abnormalities of intracellular calcium metabolism in insulin-sensitive tissues (liver, skeletal muscle, and adipocytes) and cardiovascular tissue.
Role of ACE inhibitors in treating hypertensive diabetic patients
Cardiovascular disease (CVD) is a major determining factor of morbidity and mortality in type 2 diabetic patients. Hypertension, which accompanies diabetes in more than 70% of cases, contributes to increased prevalence of CVD events in this group of patients. Results from the United Kingdom Prospective Diabetes Study (UKPDS) indicated that reduction of elevated blood pressure might decrease CVD morbidity and mortality more than reduction of hyperglycemia. Activation of circulating and tissue renin-angiotensin system (RAS) contributes to the development of both hypertension and insulin resistance in patients with the cardiometabolic syndrome. Angiotensin-converting enzyme (ACE) inhibitor therapy in patients with the cardiometabolic syndrome may improve insulin action as well as lessen CVD. In clinical trials, ACE inhibitors have been shown to be more efficient than other antihypertensive medications (i.e., calcium channel blockers) in the reduction of CVD morbidity and mortality in hypertensive diabetics. In this article, we summarize possible mechanisms by which ACE inhibition may improve insulin resistance, coagulation/clotting, and vascular function abnormalities, and postpone or even prevent the development of type 2 diabetes in hypertensive patients.
The use of ACE inhibitors on diabetic patients without renal disease
Strategies that interrupt the renin-angiotensin system, especially with angiotensin-converting enzyme (ACE) inhibition, reduce cardiovascular disease mortality and morbidity in high-risk persons such as those with the insulin resistance syndrome and diabetes mellitus. In the 1980s emphasis was placed on the renal protective effects of ACE inhibitors in patients with diabetes and proteinuria. During the past several years controlled clinical trials have demonstrated that ACE inhibition reduces cardiovascular disease (CVD) mortality and morbidity. This is especially important in patients in the United States, where 80% of excess mortality for diabetes mellitus is attributed to CVD. This article reviews the clinical trials in high-risk patients, especially those with diabetes, that shown beneficial CVD risk reduction with ACE inhibitors.