Therapeutic potential of ACE inhibitors for the treatment of hypertension in Type 2 diabetes

Type 2 diabetes mellitus is associated with hypertension. If untreated, hypertension has a major impact on the clinical course of Type 2 diabetes and its vascular complications. In this review, we discuss rationale for the use of ACE inhibitors (ACEI) in hypertensive Type 2 diabetic patients and compare those theoretical assumptions with results of recent major clinical trials. Furthermore, possible directions for future clinical and experimental research are outlined. The RAS and its effector angiotensin II are important players in a number of cardiovascular and renal disorders. Recent evidence suggests that RAS and factors functionally linked to RAS are activated in Type 2 diabetes. Therefore, there is a theoretical basis for the use of ACEI in the treatment of hypertension in diabetic patients. Some recent studies reported superior outcome in patients treated with ACEI-based antihypertensive regimens compared with non-ACEI based treatments in reducing the risk of macrovascular disease (CAPPP, FACET, ABCD) or both micro- and macrovascular complications in Type 2 diabetes (HOPE). However, at least two of the large prospective studies discussed in this review (UKPDS 38, HOT), supported by results from previously published SHEP study, have recently suggested that the degree of reduction of blood pressure, rather than the choice of a particular class of antihypertensive agent, is associated with decreased risk of cardiovascular events. Studies focusing on renal end-points suggest that ACEI have a superior antiproteinuric effect than the other agents. However, whether ACEI are more nephroprotective, as assessed by the rate of decline in renal function, still remains to be elucidated. Despite promising results from recent trials, large numbers of patients progress despite ACEI treatment. Incomplete inhibition of the RAS may underlie this phenomenon. Treatment strategies that could enhance the degree of RAS inhibition represent one possible direction for clinical research in the near future. However, it is unlikely that the course of such a complex syndrome as Type 2 diabetes could be dramatically changed by just one class of antihypertensive agents. This goal is more likely to be achieved by multifactorial intervention, reflecting the complexity of metabolic syndrome. ACEI should be viewed as an important, but not the only, part of this complex approach.