title: Insulin resistance increases circulating malondialdehyde-modified LDL and impairs endothelial function in healthy young men.
abstract: BACKGROUND
  Endothelial dysfunction is regarded as an early feature of atherosclerosis. Both LDL oxidation and insulin resistance play important roles in the pathogenesis of atherosclerosis. Recent studies have demonstrated a significant association between oxidized LDL and insulin resistance.
  
  
  METHODS
  We investigated relationships between insulin resistance, circulating malondialdehyde-modified (MDA)-LDL, and endothelial function in 36 healthy young men. Insulin sensitivity was estimated according to homeostasis model assessment of insulin resistance (HOMA-IR); we defined subjects with values of at least 2.5 as an insulin resistant (n=12) and those with values below 2.5 as insulin sensitive (n=24). We evaluated endothelial function by flow-mediated vasodilation (FMD) of brachial artery during reactive hyperemia, using high-resolution ultrasound. We also measured serum MDA-LDL by a sandwich enzyme-linked immunosorbent assay.
  
  
  RESULTS
  MDA-LDL was significantly higher (146+/-46 vs. 101+/-32 IU/l, P=0.002) and FMD was significantly lower (3.94+/-1.53 vs. 5.59+/-1.62 %, P=0.002) in the insulin-resistant group than in the insulin-sensitive group. The resistant group showed a significant inverse correlation between MDA-LDL and FMD (r=-0.675, P=0.016), while the sensitive group did not (r=0.163, NS). By multivariate regression analysis, MDA-LDL and age were determinants of FMD (R2=0.766) in the insulin-resistant group, while no variable determined FMD in the sensitive group. Nitroglycerin-induced endotheliumindependent dilation was similar in both groups.
  
  
  CONCLUSIONS
  These results suggest that the production of circulating MDA-LDL may be accelerated by insulin resistance, thus impairing endothelial function even in healthy young men.
authors.affiliation: Department of Cardiology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Mizuno
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsui
authors.forename: Akiko
authors.initials: A
authors.lastname: Imamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Numaguchi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Sakai
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Kenji
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000328:Adult; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood; D008168:Lung / Q000000981:diagnostic imaging; D008297:Male; D008315:Malondialdehyde / Q000097:blood*; D011877:Radionuclide Imaging
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde