Pinkney J H, Downs L, Hopton M, Mackness M I, Bolton C H
University of Bristol Department of Medicine, Bristol Royal Infirmary, UK.
Diabet Med. 1999 Dec;16(12):993-9. doi: 10.1046/j.1464-5491.1999.00191.x.
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.
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 Cu2+ was measured in vitro.
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) cm2; P=0.78). Diabetic LDL oxidation 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 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 (SD) plasma vitamin E levels (24.0 (6.5) to 47.5 (7.5) gmol/l; P=0.0006) and resulted in increased FMD (delta 0.00 (-0.02-0.01) vs. 0.01 (0.01-0.02)) cm2; P=0.0036), but no changes in LDL Cu2+ oxidation profiles were observed.
FMD is no different in Type 1 diabetic and non-diabetic subjects and nor are indices of lipid peroxidation and in vitro 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.
检验低密度脂蛋白（LDL）氧化易感性增加易导致1型糖尿病患者内皮功能障碍这一假说。
对46名非肾病性糖尿病患者和39名对照者进行横断面研究，对糖尿病患者进行为期3个月的、随机、安慰剂对照、双盲的每日500单位维生素E试验。通过高分辨率超声测量前臂的血流介导的血管舒张（FMD）。体外测量Cu2+介导的LDL氧化。
与对照组相比，糖尿病患者的基础和反应性前臂血流量更高（几何均数（标准差%）血流量（ml/min）分别为110.15（19.19%）对74.99（23.17%）；P = 0.045，以及344.35（20.84%）对205.17（21.48%）；P = 0.007），但FMD无差异（中位数（四分位数间距）0.00（-0.01 - 0.02）对0.02（-0.01 - 0.02）cm2；P = 0.78）。糖尿病患者LDL氧化滞后时间与扩张后肱动脉面积相关（r = 0.32；P = 0.05），但与FMD无关。糖尿病组和对照组的滞后时间、Cu2+介导的LDL总氧化、脂蛋白和维生素E浓度相似。非糖尿病患者对氧化LDL（oxLDL）的抗体滴度高于糖尿病患者，且与FMD无关。在糖尿病患者中，维生素E使血浆维生素E水平均值（标准差）升高（从24.0（6.5）至47.5（7.5）μmol/l；P = 0.0006），并使FMD增加（差值0.00（-0.02 - 0.01）对0.01（0.01 - 0.02））cm2；P = 0.0036），但未观察到LDL Cu2+氧化谱的变化。
1型糖尿病患者和非糖尿病患者的FMD无差异，脂质过氧化指标和体外LDL氧化指标也无差异，尽管糖尿病患者对oxLDL的抗体水平较低。补充维生素E可提高糖尿病患者的血浆维生素E水平，并可能增强FMD，但在LDL氧化无变化的情况下，这可能不是由LDL氧化减少介导的。
