title: Endothelial dysfunction in Type 1 diabetes mellitus: relationship with LDL oxidation and the effects of vitamin E.
abstract: 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.
authors.affiliation: University of Bristol Department of Medicine, Bristol Royal Infirmary, UK. j.pinkney@bristol.ac.uk
authors.forename: J H
authors.initials: JH
authors.lastname: Pinkney
authors.forename: L
authors.initials: L
authors.lastname: Downs
authors.forename: M
authors.initials: M
authors.lastname: Hopton
authors.forename: M I
authors.initials: MI
authors.lastname: Mackness
authors.forename: C H
authors.initials: CH
authors.lastname: Bolton
mesh_terms: 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*
chemical_list: D000975:Antioxidants; D008077:Lipoproteins, LDL; D010919:Placebos; D014810:Vitamin E; D008315:Malondialdehyde