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Mechanisms of glucose toxicity. New hope for prevention of diabetic complications?

Long-standing diabetes mellitus is characterized by the development of widespread micro- and macroangiopathy. The goal of the treatment of diabetes mellitus is to prevent both acute and long-term complications. It has been thought for a long time that the occurrence of diabetic complications depends on glycaemic control as well as genetic factors. It has now clearly been proved by the Diabetes Control and Complications Trial that hyperglycaemia is a major factor in the development of diabetes complications; intensive treatment can significantly delay the development and slow the progression of microvascular complications (1). Understanding the mechanism of glucose-induced diabetes complications is necessary to try to prevent or stop glucose toxicity. Multiple biochemical alterations have been reported in diabetes, and several metabolic pathways seem to be involved in glucose toxicity with a possible redundancy in their mechanisms: (i) insulin deficiency and hyperglycaemia enhance glucose metabolism through the polyol pathway via aldose reductase.