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.