64 Ann. N.Y. Acad. Sci. 1042: 64–69 (2005). © 2005 New York Academy of Sciences. doi: 10.1196/annals.1338.007 Increased Oxidative Damage with Altered Antioxidative Status in Type 2 Diabetic Patients Harboring the 16189 T to C Variant of Mitochondrial DNA TSU-KUNG LIN, a SHANG-DER CHEN, a PEI-WEN WANG, c YAU-HUEI WEI, b CHENG-FENG LEE, b TZU-LING CHEN, b YAO-CHUNG CHUANG, a TENG-YEOW TAN, a KU-CHOU CHANG, a AND CHIA-WEI LIOU a a Department of Neurology and c Department of Metabolism, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan b Department of Biochemistry and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan ABSTRACT: A transition of T to C at nucleotide position 16189 in mitochondrial DNA (mtDNA) has attracted biomedical researchers for its probable correla- tion with the development of diabetes mellitus in adult life. In diabetes, persis- tent hyperglycemia may cause high production of free radicals. Reactive oxygen species are thought to play a role in a variety of physiologic and patho- physiologic processes in which increased oxidative stress may play an impor- tant role in disease mechanisms. The aim of the present study was to clarify the degree of oxidative damage and plasma antioxidant status in diabetic patients and to see the potential influence of the 16189 variant of mtDNA on the oxida- tive status in these patients. An indicative parameter of lipid peroxidation, malondialdehyde (MDA), and total free thiols were measured from plasma samples of 165 type 2 diabetic patients with or without this variant and 168 normal subjects. Here we report an increase in the plasma levels of MDA and total thiols in type 2 diabetic patients compared with control subjects. The lev- els of plasma thiols in diabetic patients with the 16189 variant of mtDNA were not different from those in controls. These results suggest an increase in the oxidative damage and a compensatory higher antioxidative status in patients with type 2 diabetes. Harboring the 16189 mtDNA variant may impair the abil- ity of a cell to respond properly to oxidative stress and oxidative damage. KEYWORDS: mitochondrial DNA; T16189C polymorphism; antioxidative status; type 2 diabetes Address for correspondence: Chia-Wei Liou, M.D., Department of Neurology, Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung 833, Taiwan. Voice: +886- 7-7317123 ext. 2283; fax: +886-7-7318762. cwliou@ms22.hinet.net