Mechanisms-based therapeutic strategies in type 2 diabetes

Prevalence of diabetes mellitus (DM) is increasing rapidly, and individuals with DM are at high risk for cardiovascular (CV) disorders that affect the heart, brain and peripheral vessels. The International Diabetes Federation currently estimates that 382 million people are affected by type 2 DM (T2D), with a global age-adjusted prevalence of 10%. If these trends continue, 592 million people, or one adult in 10, will have diabetes by 2035 (1). This equates to approximately three new cases every 10 seconds or almost 10 million per year. Most importantly, a substantial proportion of affected people are unaware of their condition and do not receive treatment. Epidemiological studies have shown a strong association between T2D and the risk of CV events (2). Indeed, T2D increases the risk of micro- and macrovascular complications and it is associated with an approximate two-fold greater risk of mortality as compared with the general population (3). Metabolic alterations occurring in DM subjects, namely insulin resistance, reduced insulin secretion or their combination are responsible for endothelial dysfunction, increased platelet reactivity, inflammation and myocardial damage—all factors triggering and accelerating atherosclerotic vascular disease, coronary thrombosis and heart failure (HF). On this ground, understanding the pathophysiology of DM-related CV complications may be invaluable to elaborate novel mechanism-based therapeutic strategies to combat CVD burden associated with DM.