ACUTE HYPERGLYCEMIA AND OXIDATIVE STRESS GENERATION

Oxidative stress is an acknowledged pathogenic mechanism in diabetic c omplications. Several studies have demonstrated that acute hyperglycae mia can impair the physiological homeostasis of important systems in l iving organisms and that it may exert these effects via production of free radicals and associated oxidative stress. Acute increases in plas ma glucose concentration may increase free radical production by the f ollowing mechanisms: labile glycation; auto-oxidation of glucose; and intracellular activation of the polyol pathway, which produces an imba lance in the NADH/NAD(+) ratio and favours the production of free radi cals. The hypothesis that free radicals may mediate the effects of acu te hyperglycaemia is supported by evidence that antioxidants can count eract some of the effects induced by acute hyperglycaemia, for example , vasoconstriction, activation of coagulation, and the increase in pla sma intracellular adhesion molecule-1 concentrations. Direct evidence of an association between oxidative stress and hyperglycaemia has come from studies of induced hyperglycaemia or standardized meal intake. I n both diabetic and non-diabetic subjects, hyperglycaemia or meal inta ke causes a reduction in plasma Total Radical-trapping Antioxidant Par ameter (TRAP). This is associated with consumption of protein thiol gr oups, vitamin C, and uric acid. This may confirm the hypothesis that a cute hyperglycaemia provokes oxidative stress, which destroys the natu ral antioxidant defences found in the plasma. (C) 1997 by John Wiley & Sons, Ltd.