Cardiovascular and Renal Protection in Type 2 Diabetes Mellitus (2002)

The most important factor that prevents the progression of renal damage in diabetes mellitus, beside the improvement of blood glucose control, is tight BP control. The tenet of tight BP control may be defined as the lowest BP level one can accomplish using antihypertensive therapy that is at the same time compatible with the absence of untoward side effects. In fact, both the Framingham Heart Study in nondiabetic normal subjects and the United Kingdom Prospective Diabetes Study in type 2 diabetic patients showed that systolic values as low as 108 to 111 mmHg and diastolic values as low as 70 to 71 mmHg are significantly associated with decreased cardiovascular mortality and morbidity. However, 45 to 50% of the patients with type 2 diabetes mellitus and hypertension have systolic BP levels above 140 mmHg during antihypertensive therapy, particularly when using monotherapy. Thus the issue regarding the choice of which drugs one should use to treat hypertension became critical from a clinical point of view. Pharmaceutical compounds, which inhibit the renin-angiotensin system, have become the first-choice treatment in patients with diabetes mellitus and incipient and advanced renal complications. The present brief review analyzes the effects of calcium channel blockers (CCB) on cardiovascular and renal complications in diabetes mellitus. The review discussed those studies that directly and blindly compared CCB with angiotensin-converting enzyme (ACE) inhibitors and with angiotensin II AT(1) receptor blockers (ARB). Furthermore, size of the population recruited in each trial was used as a criterion of priority in the selection of the reports from the available literature. From the point of view of cardiovascular complications, the results of these studies showed a slightly better benefit of CCB on stroke, whereas ACE inhibitors better prevented the occurrence of myocardial infarction and congestive heart failure. On the other hand, recent observations demonstrated that also ACE inhibitors and ARB are effective in the primary and secondary prevention of stroke, although these studies did not directly compare these compounds with CCB. With regard to the outcome of renal complications, both ARB and ACE inhibitors more effectively prevented the progression of renal damage among the patients with overt nephropathy than CCB. On the contrary, both CCB and ACE inhibitors were equally effective on blunting the decay of GFR in diabetic patients who do not have overt proteinuria. However, ACE inhibitors and ARB more markedly decreased the rate of albumin excretion rate in the range of both microalbuminuria and macroalbuminuria. Recent advances in the understanding of the pathogenesis of abnormalities of albumin excretion rate and of atherosclerosis are also discussed. Both mechanical stress, mainly secondary to systolic hypertension, and elevated circulating and tissue levels of angiotensin II, partially independent from each other, cause excessive generation of superoxide compounds. This chain reaction of events in turn leads to disorders of structural components of glomerular filter and to damage of the vascular wall. Systolic BP control (<130 mmHg) is not adequately accomplished in the majority of the patients treated only with ACE inhibitors and ARB, even in association with diuretics. Poor BP control may lead to excessive systemic mechanical stress at the vascular level despite satisfactory inhibition of angiotensin II effects. In conclusion, one can suggest that CCB are useful and often indispensable pharmaceutical compounds, beside ACE inhibitors and ARB, to accomplish tight BP control (<130/85 mmHg), a target that is unlikely to be successfully maintained in the overall population of type 2 diabetic patients only by ACE inhibitors or ARB, as monotherapy. However, ACE inhibitors and ARB might be considered first-choice drugs in the treatment of hypertension in diabetes mellitus, mainly because of a better renoprotection.