Coronary heart disease (CHD) is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM) and the oxidation of low-density lipoprotein (LDL) may be an essential factor in the development of atherosclerotic lesions. Therefore, we studied the in vitro susceptibility of LDL to copper-induced oxidation in 72 NIDDM patients and 94 well-matched non-diabetic control subjects. There was no significant difference in the lagtime of LDL oxidation between NIDDM patients and control subjects (68.1+/-8.8 vs. 66.7+/-9.2 min, respectively, P=0.29). The plasma alpha-tocopherol/LDL-ratio was the most significant determinant of the lagtime in multiple regression analysis. High level of serum triglycerides was associated with decreased lagtime in control subjects, but not in NIDDM patients. Blood glucose balance was not associated with LDL susceptibility to oxidation in NIDDM patients. Subjects with CHD did not have LDL susceptibility to oxidation different from that of subjects without CHD in either of the study groups. Urinary albumin excretion or glomerular filtration rate was not associated with the lagtime of LDL oxidation in NIDDM patients. In conclusion, these data suggest that diabetes and hyperglycemia per se do not affect the susceptibility of LDL to oxidation. The presence of CHD or renal dysfunction were not associated with LDL susceptibility to oxidation.