Diabetes mellitus increases the risk for
hypertension and associated
cardiovascular diseases, including coronary, cerebrovascular, renal and
peripheral vascular disease. The risk for developing
cardiovascular disease is increased when both diabetes and
hypertension co-exist; in fact, over 11 million Americans have both diabetes and
hypertension. These numbers will continue to climb, internationally, since the leading associated risk for diabetes development,
obesity, has reached epidemic proportions, globally. Moreover, the frequent association of diabetes with
dyslipidemia, as well as coagulation, endothelial, and metabolic abnormalities also aggravates the underlying
vascular disease process in patients who possess these comorbid conditions. The renin-angiotensin-aldosterone system (RAS) and
arginine vasopressin (AVP) are overactivated in both
hypertension and diabetes. Drugs that inhibit this system, such as
ACE inhibitors and more recently
angiotensin receptor antagonists (ARBs), have proven beneficial effects on the micro- and macrovascular complications of diabetes, especially the kidney. The BRILLIANT study showed that
lisinopril reduces microalbuminuria better than CCB
therapy. Numerous other long-term studies confirm this association with
ACE inhibitors including the HOPE trial. Furthermore, the European Controlled trial of
Lisinopril in
Insulin-dependent Diabetes (EUCLID) study, showed that
lisinopril slowed the progression of renal disease, even in individuals with mild
albuminuria. In fact, there are now five appropriately powered randomized placebo-controlled trials to show that both
ACE inhibitors and ARBs slow progression of
diabetic nephropathy in people with
type 2 diabetes. These effects were shown to be better than conventional blood pressure lowering
therapy, including
dihydropyridine CCBs. In patients with microalbuminuria,
ACE inhibitors and ARBs reduce the progression of microalbuminuria to
proteinuria and provide a risk reduction of between 38 and 60% for progression to
proteinuria. This is important since microalbuminuria is known to be associated with increased vascular permeability and decreased responsiveness to vasodilatory stimuli. Recently, increased AVP levels have been lined to microalbuminuria and hyperfiltration in diabetes. The microvascular and macrovascular benefits of ACE inhibition, ARBs and possible role of AVP antagonists in diabetic patients will be discussed, as will be recommendations for its clinical use.