Oxidative Stress Contributions to Chronic Complications in Diabetes

Diabetes Mellitus is a serious global health problem. Both type 1 and type 2 diabetes markedly increase the risk of microvascular and macrovascular complications. Chronic complications of diabetes (retinopathy, nephropathy, neuropathy, and diabetes accelerated arteriosclerosis) represent a major medical and economical concern. Several pathogenic mechanisms were proposed to be responsible for the development of long-term complications of diabetes (i.e. increase polyol pathway flux, increased advanced glycation end products, activation of proteinkinase C, increased hexosamine pathway flux). A coherent pathogenic mechanism has just recently evolved by the discovery that each of the mechanisms mentioned reflects a single hyperglycemia-induced process: overproduction of reactive oxygen species by the mitochondria electron-transport chain. Oxidative stress is defined as tissue injury resulting from a disturbance in the equilibrium between the production free radicals and antioxidant defense mechanisms. In this review, we consider how glucose-induced oxidative stress may lead to microvascular and cardiovascular complications.