In Vivo Evidence for Increased Oxidation of Circulating LDL in Impaired Glucose Tolerance
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.
Address correspondence and reprint requests to Dr. Steffi Kopprasch, University of Technology Dresden, Carl Gustav Carus Medical School, Department of Internal Medicine 3, Pathological Biochemistry, Fetscherstr. 74, D-01307 Dresden, Germany. E-mail:.
Received for publication 21 January 2002 and accepted in revised form 15 July 2002.
S.K. and J.P. contributed equally to this work.
CAD, coronary artery disease; CPOA, circulating phagocyte oxygenation activity; IGT, impaired glucose tolerance; IMT, intima-media thickness; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; oxLDL, oxidized LDL; PON, serum paraoxonase activity with paraoxon as substrate; RIAD, Risk Factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes; TAC, total antioxidant capacity.