Endothelial dysfunction in Type 1 diabetes mellitus: relationship with LDL oxidation and the effects of vitamin E.
OBJECTIVE
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.
Pinkney
J H
JH
University of Bristol Department of Medicine, Bristol Royal Infirmary, UK. j.pinkney@bristol.ac.uk
Downs
L
L
Hopton
M
M
Mackness
M I
MI
Bolton
C H
CH
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D010919:Placebos; D011446:Prospective Studies; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*
D000975:Antioxidants; D008077:Lipoproteins, LDL; D010919:Placebos; D014810:Vitamin E; D008315:Malondialdehyde