Antioxidants and CVD in diabetes: where do we stand now

Abstract

Diabetes is an oxidative stress disorder as a result of both hyperglycemia and increased levels of free fatty acids. Oxidative stress has been implicated in the pathogenesis of diabetes-related complications, and treatment with antioxidants seemed to be a promising therapeutic option. Although animal studies and preliminary human studies were initially encouraging, subsequent human studies have failed to show a clear benefit of antioxidants, whereas some studies have even suggested that they can be potentially harmful. Therefore, treatment with antioxidants cannot be currently recommended as a therapeutic option.

Figure 1

The pathogenesis of oxidative stress in diabetes. Hyperglycemia can induce oxidative stress through advanced glycation end product formation, increased flux thorough the polyol pathway, increased activation of protein kinase C (PKC), and increased flux through the hexosamine pathway. Hyperglycemia can also directly increase superoxide production. In addition to an increase in free fatty acids and low-density lipoprotein (LDL), these pathways promote oxidative stress, which in turn causes endothelial dysfunction. Endothelial dysfunction is likely the first step in the development of both the micro- and macrocirculatory complications of diabetes. DAG—diacylglycerol.