HDL oxidability and its protective effect against LDL oxidation in Type 2 diabetic patients

Low density lipoprotein (LDL) oxidation is a crucial step in the atheroscle rotic process. High density lipoprotein (HDL)-associated enzymes such as pa raoxonase could exert a protective effect on LDL oxidation in the arterial wall, an effect which could be impaired in Type 2 diabetes mellitus (T2DM). We studied copper-induced oxidation in LDL and HDL isolated from 17 T2DM p atients with fair glycaemic control and HDL-cholesterol within normal range and 17 healthy normolipidaemic control subjects. To evaluate the effect of HDL on LDL oxidation in diabetic and control subjects, we assessed copper- induced oxidation in HDL/LDL mixtures, with each lipoprotein isolated from the same subject. Relationships with HDL chemical composition, a-tocopherol content and serum paraoxonase activity were investigated. Oxidation was pr omoted by lipoprotein incubation with copper and then thiobarbituric acid r eactive substances (TBARS), conjugated diene production and electrophoretic mobility in agarose gel were measured. In T2DM subjects HDL oxidation was higher than in controls. However, HDL from diabetics was as effective as co ntrol HDL to inhibit LDL oxidation, Neither HDL chemical composition nor se rum paraoxonase activity showed any difference as compared to control subje cts. In contrast, HDL from T2DM subjects showed a higher a-tocopherol conte nt which positively correlated with HDL oxidability. Paraoxonase activity p ositively and strongly correlated with HDL inhibitory effect on LDL oxidati on in patients and controls belonging to the heterozygous activity phenotyp e, Besides, LDL oxidability showed no differences between patients and cont rols. These results suggest that fairly-controlled T2DM patients with HDL-c holesterol levels within normal range show: 1) normal HDL ability to inhibi t LDL oxidation related to normal paraoxonase activity; 2) higher HDL oxida bility in spite of its high a-tocopherol content, which could favour tocoph erol-mediated peroxidation and 3) normal LDL oxidability possibly due to th e lack of significant lipoprotein structural alterations. (C) 2001, Editric e Kurtis.