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

<jats:title>Summary</jats:title><jats:p> <jats:bold>Aims</jats:bold> 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.</jats:p><jats:p> <jats:bold>Methods</jats:bold> A cross‐sectional study of 46 non‐nephropathic diabetic and 39 control 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 ultrasound. LDL oxidation by Cu<jats:sup>2</jats:sup> +  was measured <jats:italic>in vitro</jats:italic>.</jats:p><jats:p> <jats:bold>Results</jats:bold> Diabetic patients had greater basal and reactive forearm blood flow (geometric mean ( <jats:sc>sd</jats:sc>%) flow (ml/min) 110.15 (19.19%) vs. 74.99 (23.17%); <jats:italic>P</jats:italic>=  0.045, and 344.35 (20.84%) vs. 205.17 (21.48%); <jats:italic>P</jats:italic>=  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<jats:sup>2</jats:sup>; <jats:italic>P</jats:italic>=  0.78). Diabetic LDL oxidation lag time correlated with postdilatation brachial artery area (<jats:italic>r</jats:italic>=  0.32; <jats:italic>P</jats:italic>=  0.05) but not with FMD. Lag‐times and total LDL oxidation by Cu<jats:sup>2</jats:sup> + , lipoprotein and vitamin E concentrations were similar in diabetic and control groups. Antibody titres to oxidized LDL (oxLDL) were higher in non‐diabetic than diabetic subjects, and were unrelated to FMD. In diabetic patients, vitamin E increased mean ( <jats:sc>sd</jats:sc>) plasma vitamin E levels (24.0 (6.5) to 47.5 (7.5) μmol/l; <jats:italic>P</jats:italic>=  0.0006) and resulted in increased FMD (Δ 0.00 ( − 0.02–0.01) vs. 0.01 (0.01–0.02)) cm<jats:sup>2</jats:sup>; <jats:italic>P</jats:italic>=  0.0036), but no changes in LDL Cu<jats:sup>2</jats:sup> +  oxidation profiles were observed.</jats:p><jats:p> <jats:bold>Conclusions</jats:bold> FMD is no different in Type 1 diabetic and non‐diabetic subjects and nor are indices of lipid peroxidation and <jats:italic>in vitro</jats:italic> LDL oxidation although levels of antibody to oxLDL are lower in diabetes. Vitamin E supplementation increases plasma vitamin E levels and may enhance FMD in diabetes but, in the absence of changes in LDL oxidation, this may not be mediated by reduced oxidation of LDL.</jats:p>