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Am J Physiol Heart Circ Physiol 285: H2392-H2398, 2003. First published July 24, 2003; doi:10.1152/ajpheart.00403.2003
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Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus

Joshua A. Beckman,1 Allison B. Goldfine,2 Mary Beth Gordon,1 Leslie A. Garrett,1 John F. Keaney, Jr.,3 and Mark A. Creager1

1Cardiovascular Division, Brigham and Women's Hospital, and 2Division of Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston 02115; and 3Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118

Submitted 1 May 2003 ; accepted in final form 17 July 2003

Oxidative stress decreases the bioavailability of endothelium-derived nitric oxide in diabetic patients. We investigated whether impaired endothelium-dependent vasodilation (EDV) in diabetes can be improved by long-term administration of oral antioxidants. Forty-nine diabetic subjects [26 Type 1 (T1) and 23 Type 2 (T2)] and 45 matched healthy control subjects were randomized to receive oral vitamin C (1,000 mg) and vitamin E (800 IU) daily or matching placebo for 6 mo. Vascular ultrasonography was used to determine brachial artery EDV and endothelium-independent vasodilation (EIV). EDV was decreased in both T1 (4.9 ± 0.9%, P = 0.015) and T2 (4.1 ± 1.0%, P < 0.01) subjects compared with control subjects (7.7 ± 0.7%). EIV was decreased in T2 (15.0 ± 1.2%, P < 0.01) but not T1 subjects (18.5 ± 2.3%, P = 0.3) compared with controls (21.8 ± 1.8%). Administration of antioxidant vitamins increased EDV in T1 (by 3.4 ± 1.4%, P = 0.023) but not T2 subjects (by 0.5. ± 0.4%, P = 0.3). Antioxidant therapy had no signigicant affect on EIV. Oral antioxidant therapy improves EDV in T1 but not T2 diabetes. These results are consistent with the lack of clinical benefit in studies that have included primarily T2 diabetic patients.

endothelium; nitric oxide


Address for reprint requests and other correspondence: M. A. Creager, Cardiovascular Div., Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115 (E-mail: mcreager{at}partners.org).




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