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.