The changing epidemiology of human type 2 diabetes–associated atherosclerosis: Pathophysiological mechanisms and emerging treatment possibilities

Type 2 diabetes (T2D) is a major global health concern strongly associated with atherosclerosis and subsequent macrovascular complications. These complications are the leading cause of death among T2D patients. Despite a decline in cardiovascular events over the last decade, individuals with T2D still have an approximately doubled risk compared to those without diabetes. This shows an urgent need for therapies targeting biological processes specific to T2D-associated atherosclerosis. Nevertheless, more research is needed to identify exactly which processes can be targeted therapeutically. Current therapies either target lipid metabolism or inflammation, two processes commonly considered important in T2D-associated atherosclerosis. However, more recent human plaque tissue studies show no differences in plaque levels of lipids nor inflammatory markers, possibly reflecting improved clinical treatment strategies. Other distinct differences in plaque tissue composition in T2D have been put forward, including thin fibrous caps and large necrotic cores. Moreover, T2D may influence several biological processes affecting both plaque formation and progression (such as oxidative stress and efferocytosis). These mechanisms could potentially also be targeted to prevent atherosclerotic cardiovascular complications. This review focuses on the shifting epidemiology of T2D-associated cardiovascular complications, as well as biological changes in T2D plaques, and how these changes can guide future clinical approaches to further reduce atherosclerotic complications.