A new sensitive and reproducible method was used to assess LDL oxidative status in Type 2 diabetic patients and control subjects, and the relationships between LDL oxidation and atherosclerosis or nephropathy were determined. LDL oxidation was measured in 35 patients with Type 2 diabetes and 15 control subjects 40 to 60 years of age. Atherosclerosis was assessed by clinical examination, vascular ultrasound, and measurement of intima-media thickness (IMT). Twenty-four hour urinary albumin excretion measurements were performed. Although no differences in lipid values were found between the 22 diabetic patients with atherosclerosis (ATS+) and the 13 without (ATS-), LDL oxidation was significantly higher in ATS+ than ATS- patients (p = 0.009) or control subjects (p = 0.007). LDL oxidation was also increased in the 15 patients with nephropathy (p = 0.003). Oxidation was correlated with IMT in patients with normal to moderately increased IMT ( < or = 1.05 mm). Determination of LDL oxidative status could thus be very helpful in assessing cardiovascular risk, especially in high-risk subjects such as patients with diabetes mellitus.