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Am Fam Physician. 2003;68(5):962-967

The prevalence of type 2 diabetes is increasing because the population is aging and becoming more obese and more sedentary. Diabetes has become the most common cause of new blindness, end-stage renal disease, and lower limb amputations in the United States. Other complications of diabetes include cardiovascular disease, stroke, and early mortality. Recent research has demonstrated the important role of the renin-angiotensin aldosterone system in the increased risk for hypertension and cardiovascular disease in patients with type 2 diabetes.

McFarlane and Sowers reviewed the role of aldosterone as an added risk factor to angiotensin II for cardiovascular disease in persons who have diabetes. The presence of type 2 diabetes is a risk factor for cardiovascular disease and also accentuates the risk brought on by hypertension, smoking, and dyslipidemia. Diabetic renal disease and vascular disease move ahead concurrently in persons with type 2 diabetes. Albuminuria is a predictor of cardiovascular disease and stroke as well as diabetic renal disease. Activation of the renin-angiotensin system (RAS) negatively affects the renal glomerulus as well as the vascular system. The relationship of RAS activation to heart failure and stroke incidence and severity also has been documented. The reduction of blood pressure in persons with type 2 diabetes who use an angiotensin-converting enzyme (ACE) inhibitor significantly reduces stroke risk. Recent data point to a similar risk reduction with the use of an angiotensin-receptor blocking (ARB) agent.

Aldosterone, a steroid hormone produced in the outer layer of the adrenal cortex, promotes renal sodium retention and potassium loss. Secretion changes occur in response to alterations of volume status or salt intake mediated by angiotensin II. Aldosterone reduces baroreflex sensitivity and enhances sympathetic activity resulting in reduced nitric oxide–mediated vasorelaxation. This results in reduced serum potassium levels and an increase in left ventricular mass and cardiac output. The aldosterone antagonist spironolactone reduces morbidity and mortality in patients with severe heart failure. The procoagulant properties of aldosterone with inhibition of fibrinolysis potentiate atherosclerosis. Renal glomerulus dysfunction results from basement membrane abnormalities, nephrosclerosis, and renal fibrosis induced by aldosterone, and leads to microalbuminuria.

The authors conclude that aldosterone has detrimental effects on the vasculature, cardiac tissue, renal mesangial cells, and the brain, as well as deleterious effects on baroreflex sensitivity and the autonomic nervous system. Blocking aldosterone actions may have positive cardiovascular and renal effects. Further studies are needed to investigate the efficacy of ACE inhibitor/ARB combinations and aldosterone antagonists in reduction of renal and cardiovascular disease in persons with type 2 diabetes.

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