Vascular dysfunction in Type 2 diabetes: emerging targets for therapy

Abstract

Vascular dysfunction associated with Type 2 diabetes is initially manifested in the pre-diabetic condition and continuously expressed as this complex disease progresses to include other cardiovascular complications that collectively increase patient risk to morbidity and mortality. Many factors are known to affect vascular function and this review focuses on the role of adipokines and obesity in this process. Growing evidence suggests that adipose-derived adipokines, such as cytokines, chemokines and hormones, plays a significant role in the regulation of vascular function. Inhibition of vascular reactive oxygen species (ROS) formation and lowering plasma free fatty acid level are all potential therapeutic targets for type 2 diabetes-induced vascular dysfunction. Bariatric surgery is a relatively new and more aggressive treatment for the morbidly obese patient that also results in an instant and obvious improvement of vascular function through as yet unexplained mechanisms. These therapies show great promise for the prevention and cure of diabetes-induced vascular dysfunction.

Figure 1

Schematic flow of obesity and type 2 diabetes-induced vascular dysfunction. Type 2 diabetes results in vascular dysfunction through the increase in 1) adiposity (blue), 2) NAPDH oxidase-induced ROS production in vasculature (green), and 3) hyperglyceridemia (yellow). Increased adiposity in obesity and type 2 diabetes is associated with adverse expression pattern of various adipose-derived hormones, inflammatiory cytokines and chemokines, and enhanced adipose inflammatory cell infiltration. Enhanced O^.−₂ radical production through TNF-α and AGE/RAGE signaling reduces NO bioavailability and results in impairment of vascular function. Diverse processes induced by hypertriglyceridemia lead to the generation of endothelial dysfunction and the onset of vascular diseases via decreased bioavailability of NO.