[Frontiers in Bioscience 14, 192-209, January 1, 2009]
Therapeutic interventions and oxidative stress in diabetes
Shilpa Rahangdale1, Susie Yim Yeh2, Atul Malhotra2, Aristidis Veves3
1Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston MA, USA, 2Sleep Medicine and Pulmonary/Critical Care Divisions, Brigham and Women's Hospital and Harvard Medical School, Boston MA, USA, 3Microcirculation Laboratory Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA, USA.
TABLE OF CONTENTS
Many therapeutic agents that are used in patients with diabetes mitigate oxidative stress. These agents are of particular interest because oxidative stress is elevated in diabetes and is thought to contribute to vascular dysfunction. Agents that merely quench already formed reactive oxygen species have demonstrated limited success in improving cardiovascular outcomes. Thus, although vitamin E, C, and alpha lipoic acid appeared promising in animal models and initial human studies, subsequent larger trials have failed to demonstrate improvement in cardiovascular outcomes. Drugs that limit the production of oxidative stress are more successful in improving vascular outcomes in patients with diabetes. Thus, although statins, ACE inhibitors, ARBs and thiazolinediones are used for varied clinical purposes, their increased efficacy in improving cardiovascular outcomes is likely related to their success in reducing the production of reactive oxygen species at an earlier part of the cascade, thereby more effectively decreasing the oxidative stress burden. In particular, statins and ACE inhibitors/ ARBs appear the most successful at reducing oxidative stress and vascular disease and have potential for synergistic effects.