7-KETOCHOLESTEROL, A SPECIFIC INDICATOR OF LIPOPROTEIN OXIDATION, ANDMALONDIALDEHYDE IN NON-INSULIN-DEPENDENT DIABETES AND PERIPHERAL VASCULAR-DISEASE

Increased free radical-mediated lipoprotein oxidation may contribute t o the increased prevalence of atherosclerosis in non-insulin dependent diabetes. We have determined levels of malondialdehyde (MDA) and 7-ke tocholesterol, 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 h igh density lipoprotein fractions of serum separated by sequential flo tation 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 pati ents with peripheral vascular disease (PVD). MDA was increased in vasc ular 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 diabe tic patients (3.8 (3.0-4.8) mu mol/l). There were no significant diffe rences in 7-ketocholesterol concentration in LDL, but calculated total 7-ketocholesterol was lower in non-diabetic vascular patients than co ntrols (P < 0.01). Vitamin C concentration was reduced in diabetic and non-diabetic patients with vascular disease. No significant differenc e in concentration of vitamin E or A was found. In six normal subjects the concentration of MDA was low in lipoproteins separated by ultrace ntrifugation but high in the residue following lipoprotein fractionati on (70-80% total serum MDA). In conclusion, the concentration of MDA b y the thiobarbituric acid assay in untreated serum may not reflect fre e radical damage to lipoproteins. There was no evidence of increased l ipoprotein oxidation using 7-ketocholesterol in NIDDM or PVD. (C) 1997 Elsevier Science B.V.