Insulin resistance increases circulating malondialdehyde-modified LDL and impairs endothelial function in healthy young men.
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.
Mizuno
Tomofumi
T
Department of Cardiology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
Matsui
Hideo
H
Imamura
Akiko
A
Numaguchi
Yasushi
Y
Sakai
Kazuyoshi
K
Murohara
Toyoaki
T
Okumura
Kenji
K
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
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde