7-ketocholesterol, a specific indicator of lipoprotein oxidation, and malondialdehyde in non-insulin dependent diabetes and peripheral vascular disease

Increased free radical-mediated lipoprotein oxidation may contribute to the increased prevalence of atherosclerosis in non-insulin dependent diabetes. We have determined levels of malondialdehyde (MDA) and 7-ketocholesterol, a specific indicator of free radical-mediated oxidation of lipoprotein cholesterol, in serum in very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein (LDL) and high density lipoprotein fractions of serum separated by sequential flotation ultracentrifugation. Four groups of male subjects were studied: normal controls, diabetic patients with no evidence of microvascular complications or macrovascular disease, diabetic and non-diabetic patients with peripheral vascular disease (PVD). MDA was increased in vascular disease patients (diabetic 4.5 (3.7-5.8), non-diabetic 4.4 (3.2-5.7) mu mol/l, median (2.5-97.5 percentiles)) than controls (3.6 (2.9-5.0) mu mol/l) (P < 0.01), but was not increased in uncomplicated diabetic patients (3.8 (3.0-4.8) mu mol/l). There were no significant differences in 7-ketocholesterol concentration in LDL, but calculated total 7-ketocholesterol was lower in non-diabetic vascular patients than controls (P < 0.01). Vitamin C concentration was reduced in diabetic and non-diabetic patients with vascular disease. No significant difference in concentration of vitamin E or A was found. In six normal subjects the concentration of MDA was low in lipoproteins separated by ultracentrifugation but high in the residue following lipoprotein fractionation (70-80% total serum MDA). In conclusion, the concentration of MDA by the thiobarbituric acid assay in untreated serum may not reflect free radical damage to lipoproteins. There was no evidence of increased lipoprotein oxidation using 7-ketocholesterol in NIDDM or PVD. (C) 1997 Elsevier Science B.V.