The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN,the American Diabetes Association and the German Diabetes Society

This review summarises the results and discussions of an UNESCO-MCBN suppor ted symposium on oxidative stress and its role in the onset and progression of diabetes. There is convincing experimental and clinical evidence that t he generation of reactive oxygen species (ROI) is increased in both types o f diabetes and that the onset of diabetes is closely associated with oxidat ive stress. Nevertheless there is controversy about which markers of oxidat ive stress are most reliable and suitable for clinical practice. There are various mechanisms that contribute to the formation of ROI. It is generally accepted that vascular cells and especially the endothelium become one maj or source of ROI. An important role of oxidative stress for the development of vascular and neurological complications is suggested by experimental an d clinical studies. The precise mechanisms by which oxidative stress may ac celerate the development of complications in diabetes are only partly known . There is however evidence for a role of protein kinase C, advanced glycat ion end products (AGE) and activation of transcription factors such as NF k appaB, but the exact signalling pathways and the interactions with ROI rema in a matter of discussion. Additionally, results of very recent studies sug gest a role for ROI in the development of insulin resistance. ROI interfere with insulin signalling at various levels and are able to inhibit the tran slocation of GLUT4 in the plasma membrane. Evidence for a protective effect of antioxidants has been presented in experimental studies, but conclusive evidence from patient studies is missing. Large-scale clinical trials such as the DCCT Study or the UKPDS Study are needed to evaluate the long-term effects of antioxidants in diabetic patients and their potential to reduce the medical and socio-economic burden of diabetes and its complications. Co pyright (C) 2001 John Wiley & Sons, Ltd.