The renin–angiotensin–aldosterone system: a pivotal role in insulin sensitivity and glycemic control

Abstract

Diabetes mellitus is an exploding epidemic costing billions of dollars yearly. Type 2 diabetes mellitus is characterized by insulin resistance and is closely associated with arterial hypertension. Emerging literature has demonstrated that modulation of the renin-angiotensin-aldosterone system by use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers leads to improved insulin sensitivity, glycemic control and possibly prevention of type 2 diabetes mellitus. Several major studies investigating angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use in either hypertensive or heart failure patients have found lower incidence of type 2 diabetes mellitus when compared with placebo, beta-blocker, calcium-channel blocker or diuretic. None of these trials, however, studied prevention of diabetes as a primary endpoint. The Dream Trial and upcoming NAVIGATOR, ONTARGET/TRANSCEND trials specifically look at the prevention of diabetes as a primary endpoint. Several studies have evaluated possible mechanisms of how the renin-angiotensin-aldosterone system can alter insulin sensitivity and glycemic control. This review will focus on the recent literature that demonstrates renin-angiotensin-aldosterone system modulation and its effects on diabetes prevention, glycemic control and insulin sensitivity, as well as possible mechanisms for achieving this goal.