OBJECTIVE: To investigate differences in LDL oxidizability by glycemic status within the Insulin Resistance Atherosclerosis Study cohort. RESEARCH DESIGN AND METHODS: LDL oxidizability (lag time and oxidation rate) after exposure to copper was compared among 352 subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), newly diagnosed type 2 diabetes, and known type 2 diabetes. RESULTS: After adjustment for age, clinic, ethnicity, sex, and smoking status, LDL oxidation rates differed by glycemic status (P = 0.001), with a strong trend (P = 0.0001) for reduced LDL oxidation rate with increasing extent and duration of glucose intolerance (2,378 +/- 54, 2,208 +/- 65, 2,145 +/- 71, and 2,115 +/- 48 arbitrary units [mean +/- SE] for NGT, IGT, newly diagnosed type 2 diabetes, and known type 2 diabetes, respectively). Differences in LDL oxidation rate among groups were relatively unaltered by adjustment for lipids and lipoproteins, hypertension, BMI, and waist-to-hip ratio (WHR) and remained significant even after further adjustment for dietary antioxidants and fatty acids, as well as medications. LDL lag times differed marginally by glycemic status (P = 0.058), with similar values for NGT, IGT, and newly diagnosed type 2 diabetes (57-60 min) but higher values for known type 2 diabetes (65 +/- 2). These differences were eliminated by further adjustment for lipids and lipoproteins, hypertension, BMI, and WHR. CONCLUSIONS: We found that glycemic status influenced LDL oxidizability, with a paradoxical reduction in LDL oxidizability, as indicated by a lower LDL oxidation rate with increased extent and duration of glucose intolerance. This difference was only slightly attenuated by adjustment for relevant demographic, metabolic, dietary, and pharmacological factors that potentially influence LDL oxidation.