Oxidative stress and diabetic complications

Oxidative stress is an acknowledged pathogenetic mechanism in diabetic complications. Several studies demonstrate that an acute increase in the blood glucose level may impair the physiological homeostasis of many systems in the living organisms. The production of free radicals in relationship with an acute increase of plasma glucose may occur, at least, in three different ways: during labile glycation, directly from glucose through a mechanism of auto-oxidation, and by the intracellular activation of the polyol pathway. The hypothesis that free radicals may be the mediators of the effects of acute hyperglycemia is supported by the evidence that antioxidants can counteract some effects induced acutely by hyperglycemia, such as vasoconstriction, activation of coagulation and the increase of ICAM-1 plasma level. A more direct evidence comes from finding showing that during either induced hyperglycemia or standardized meal, in both normal and diabetic subjects, there is a reduction of plasma TRAP (Total Radical-Trapping Antioxidant Parameter) level, due to the consuption of protein thiol groups, vitamin C and uric acid. This would confirm that acute plasma glucose increase generates an oxidative stress which destroys the natural anti-oxidant defences of plasma. Moreover, it has been suggested that insulin resistance may be accompanied by intracellular production of free radicals. These data allow us to hypothesize that a vicious circle between hyperinsulinemia and free radicals could be operating: insulin resistance might cause elevated plasma free radical concentration which, in turn, might be responsible for a deterioration of insulin action, being hyperglycemia a contributory factor.