Acute hyperglycemia and oxidative stress: direct cause and effect?

Oxidative stress is increased in Type 2 diabetes and this appears to underlie the development of diabetic complications. Increased oxidative stress is claimed to be triggered directly by acute (sudden-onset) hyperglycemia, but published data do not clearly support a direct cause and effect relationship. In this article, published evidence of a direct prooxidant effect of acute hyperglycemia is presented and discussed in some detail, and conflicts, controversies, and problems are highlighted. Evidence for glucose variability as a possible important trigger of oxidative stress in diabetes is reviewed, with some speculation as to how the field would be advanced if there were more widespread recognition about the role that wide fluctuations in glucose concentration play in diabetic complications. Possible direct or indirect antioxidative effects of various drugs used in the treatment of diabetic subjects are discussed because these may have influenced current understanding of the link between hyperglycemia and oxidative stress. The aims are to reveal the divergence between the available evidence and the accepted view that acute hyperglycemia is a direct trigger of oxidative stress and to suggest areas of research that will help resolve current controversies in this important and challenging area.