1型糖尿病中的内皮功能障碍：与低密度脂蛋白氧化的关系及维生素E的作用。

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

作者信息

Pinkney J H, Downs L, Hopton M, Mackness M I, Bolton C H

机构信息

University of Bristol Department of Medicine, Bristol Royal Infirmary, UK.

出版信息

Diabet Med. 1999 Dec;16(12):993-9. doi: 10.1046/j.1464-5491.1999.00191.x.

DOI:10.1046/j.1464-5491.1999.00191.x

PMID:10656227

Abstract

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 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.

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) 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.

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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。