Endothelial dysfunction in Type 1 diabetes mellitus: relationship with LDLoxidation and the effects of vitamin E

Aims To examine the hypothesis that increased susceptibility of low density lipoproteins (LDL) to oxidation predisposes to endothelial dysfunction in patients with Type 1 diabetes mellitus. Methods A cross-sectional study of 46 non-nephropathic diabetic and 39 cont rol subjects and in the diabetic patients, a 3-month duration, randomized, placebo-controlled double-blind trial of vitamin E 500 U/day. Flow-mediated vasodilatation (FMD) was measured in the forearm by high resolution ultras ound. LDL oxidation by Cu2+ was measured in vitro. Results Diabetic patients had greater basal and reactive forearm blood flow (geometric mean (sd%) flow (ml/min) 110.15 (19.19%) vs. 74.99 (23.17%); P = 0.045, and 344.35 (20.84%) vs. 205.17 (21.48%); P = 0.007), compared with controls, but there was no difference in FMD (median (interquartile range) 0.00 (-0.01-0.02) vs. 0.02 (-0.01-0.02) cm(2); P = 0.78). Diabetic LDL oxi dation lag time correlated with postdilatation brachial artery area (r = 0. 32; P = 0.05) but not with FMD. Lag-times and total LDL oxidation by Cu2+, lipoprotein and vitamin E concentrations were similar in diabetic and contr ol groups. Antibody titres to oxidized LDL (oxLDL) were higher in non-diabe tic than diabetic subjects, and were unrelated to FMD. In diabetic patients , vitamin E increased mean (sd) plasma vitamin E levels (24.0 (6.5) to 47.5 (7.5) mu mol/l; P = 0.0006) and resulted in increased FMD (Delta 0.00 (-0. 02-0.01) vs. 0.01 (0.01-0.02)) cm(2); P = 0.0036), but no changes in LDL Cu 2+ oxidation profiles were observed. Conclusions FMD is no different in Type 1 diabetic and non-diabetic subject s and nor are indices of lipid peroxidation and in vitro LDL oxidation alth ough levels of antibody to oxLDL are lower in diabetes. Vitamin E supplemen tation increases plasma vitamin E levels and may enhance FMD in diabetes bu t, in the absence of changes in LDL oxidation, this may not be mediated by reduced oxidation of LDL.