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Lack of Association between Serum Paraoxonase 1 Activities and Increased Oxidized Low-Density Lipoprotein Levels in Impaired Glucose Tolerance and Newly Diagnosed Diabetes Mellitus

Department of Internal Medicine 3 (S.K., J.G.) and Institute of Medical Informatics and Biometry (E.K.), Carl Gustav Carus Medical School, University of Technology Dresden, Dresden D-01307; and Institute of Bioinorganic and Radiopharmaceutical Chemistry (J.P.), Research Centre Rossendorf, Dresden D-01314, Germany

Address all correspondence and requests for reprints to: Dr. Steffi Kopprasch, University of Technology Dresden, Carl Gustav Carus Medical School, Department of Internal Medicine 3, Pathological Biochemistry, Fetscherstrasse 74, D-01307 Dresden, Germany. E-mail: Steffi.Kopprasch{at}mailbox.tu-dresden.de.

Several in vitro investigations showed that serum paraoxonase 1 (PON1) that is located on high-density lipoprotein reduces or prevents low-density lipoprotein (LDL) oxidation and therefore retards atherosclerosis. Accordingly, the well documented loss of PON1 activity in patients with overt diabetes mellitus was causally related to the development of micro- and macroangiopathy in the disease course. Because vascular complications start already in prediabetic states, e.g. impaired glucose tolerance (IGT), we investigated serum PON1 activities and circulating levels of oxidized LDL (oxLDL) in 125 IGT subjects, 75 patients with newly diagnosed diabetes mellitus type 2, and 403 individuals with normal glucose tolerance. Using three different substrates (paraoxon, phenylacetate, p-nitrophenylacetate) we found that PON1 activity is not significantly altered in IGT and diabetes mellitus subjects, respectively, when compared with normoglycemic controls. Both IGT subjects and diabetes mellitus patients had significantly increased levels of oxLDL in the circulation. However, serum PON1 activity variations and glutamine/arginine phenotype were not related to the levels of oxLDL. The data suggest that 1) PON1 activity loss is an event occurring later in the course of diabetes mellitus; and 2) PON1 does not affect oxidation of circulating LDL, at least in early diabetes mellitus.

This study was supported by Grant 01ZZ9604 from the Federal Ministry of Education and Research, Germany.

Abbreviations: DM, Diabetes mellitus type 2; HDL, high-density lipoprotein; HOMA, homeostasis model assessment; IGT, impaired glucose tolerance; LDL, low-density lipoprotein; NGT, normal glucose tolerance; oxLDL, oxidized LDL; oGTT, oral glucose tolerance test; PON1, paraoxonase 1; Q/R, glutamine/arginine.