Renin–angiotensin-system blockade in the prevention of diabetes

Type 2 diabetes often occurs in association with hypertension and cardiovascular disease, and markedly increases cardiovascular risk. Strategies to reduce the incidence of diabetes in patients with cardiovascular disease or at high risk for such disease are therefore important. Certain classes of antihypertensive agents, namely the thiazide diuretics and beta-blockers, have an adverse impact on the metabolic profile and increase the risk for new-onset diabetes in hypertensive subjects. In contrast, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which are blockers of the renin–angiotensin system (RAS), have been shown to increase insulin sensitivity. They may also reduce the risk of diabetes in patients with hypertension or cardiovascular disorders. Some of the evidence in favour of ACE inhibitors and ARBs has come from studies with active comparators that have potential adverse metabolic effects. However, the Candesartan in Heart failure—Assessment of Reduction in Mortality and morbidity (CHARM) programme demonstrated that the ARB candesartan reduced the incidence of diabetes in heart failure patients in comparison to placebo. The mechanisms responsible for the beneficial effects of RAS blockade remain to be established. Nevertheless, a treatment that can control hypertension and reduce the risk of onset of type 2 diabetes at the same time is certainly desirable.