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Endothelial dysfunction in Type 1 diabetes mellitus: relationship with LDL oxidation and the effects of vitamin E
Author(s) -
Pinkney J. H.,
Downs L.,
Hopton M.,
Mackness M. I.,
Bolton C. H.
Publication year - 1999
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1046/j.1464-5491.1999.00191.x
Subject(s) - medicine , brachial artery , endocrinology , diabetes mellitus , interquartile range , vitamin e , endothelial dysfunction , hypertriglyceridemia , cholesterol , antioxidant , triglyceride , blood pressure , biochemistry , chemistry
Summary 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 Cu 2 + 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 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 Cu 2 + , 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) μmol/l; P = 0.0006) and resulted in increased FMD (Δ 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 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.