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In Vivo Evidence for Increased Oxidation of Circulating LDL in Impaired Glucose Tolerance

¹ Department of Internal Medicine 3, Carl Gustav Carus Medical School, University of Technology Dresden, Dresden, Germany
² Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Center Rossendorf, Dresden, Germany
³ Institute of Medical Informatics and Biometry, Carl Gustav Carus Medical School, University of Technology Dresden, Dresden, Germany
⁴ Institute and Policlinic of Clinical Metabolic Research, Carl Gustav Carus Medical School, University of Technology Dresden, Dresden, Germany
⁵ Centre for Clinical Studies GWT, Dresden, Germany

Oxidized LDL (oxLDL) is a key mediator in atherogenesis and a marker of coronary artery disease (CAD). Type 2 diabetes is associated with excessive cardiovascular morbidity and mortality. Because atherogenesis starts before diabetes is diagnosed, we investigated whether circulating oxLDL levels are increased in impaired glucose tolerance (IGT). OxLDL levels were measured in 376 subjects with normal glucose tolerance (NGT), 113 patients with IGT, and 54 patients with newly diagnosed type 2 diabetes. After correction for age and BMI, serum levels of oxLDL were significantly increased in IGT versus NGT subjects (P = 0.002). OxLDL levels were not associated with the following parameters of the oxidative/antioxidative balance in the blood: total antioxidant capacity, urate-to-allantoin ratio, and circulating phagocyte oxygenation activity. In stepwise multivariate analysis, LDL cholesterol (P < 0.0005) and triglycerides (P < 0.0005) were the strongest predictors of circulating oxLDL levels, followed by HDL cholesterol (P = 0.003), 2-h postchallenge C-peptide (P = 0.011), fasting free fatty acids (P = 0.013), and serum paraoxonase activity (P = 0.035). The strong correlation of oxLDL with LDL cholesterol and triglycerides indicates that LDL oxidation in IGT is preferentially associated with dyslipidemia. OxLDL increase may explain the high atherogenic potency of dyslipidemia in the prediabetic state.

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