Does interference with the renin-angiotensin system protect against diabetes? Evidence and mechanisms

Agents interfering with the renin-angiotensin system (RAS) system were consistently shown to lower the incidence of type 2 diabetes (T2DM), as compared to other antihypertensive drugs, in hypertensive high-risk populations. The mechanisms underlying this protective effect of RAS blockade using angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) on glucose metabolism are not fully understood. In this paper, we will review the evidence from randomized-controlled trials and discuss the proposed mechanisms as to how RAS interference may delay the onset of T2DM. In particular, since T2DM is characterized by beta-cell dysfunction and obesity-related insulin resistance, we address the mechanisms that underlie RAS blockade-induced improvement in beta-cell function and insulin sensitivity.