Abstract
A linchpin of the cardiometabolic syndrome is insulin resistance, an important cardiovascular and chronic kidney disease risk factor. Activation of the renin‐angiotensin‐aldosterone system (RAAS) has been shown to impair insulin metabolic signaling and insulin‐stimulated glucose uptake as well as pancreatic secretion of insulin. Recent work has highlighted the role of aldosterone as an important component of the RAAS and may play a role in not only altering glucose uptake in skeletal muscle but in normal liver metabolism as well. Like angiotensin II, aldosterone may promote hepatosteatosis and impact pancreatic β‐cells. By blocking the effects of angiotensin II with a RAAS blocker or aldosterone with a mineralocorticoid inhibitor, the effects may be reversed. Therefore, it appears that the RAAS and aldosterone are important in generation of reactive oxygen species in the β‐cell and increased apoptosis. It is clear that preclinical evidence has demonstrated a role for the RAAS and glucose metabolism. While there is sufficient clinical data to support RAAS inhibition with either an angiotensin‐converting enzyme inhibitor or an angiotensin receptor blocker, it is important to note none of these studies were powered to address glucose tolerance as a primary end point. Thereby, to complement preclinical studies, more randomized multicenter outcomes evidence is needed to fully elucidate the impact that RAAS inhibition and, specifically, the use of angiotensin receptor blockers have on glucose tolerance. Nonetheless, the weight of evidence suggests that inhibition of the RAAS vs other antihypertensive agents, whether calcium channel blockers, thiazide diuretics, or β‐blockade, improve glucose tolerance.