Autoantibodies against oxidized LDL and endothelium-dependent vasodilation in insulin-dependent diabetes mellitus

Abstract

We determined whether autoantibodies against oxidized LDL are increased in patients with IDDM, and if so, whether they are associated with endothelial dysfunction in vivo. Autoantibodies against oxidized LDL (ratio of antibodies against oxidized vs. native LDL, oxLDLab) were determined in 38 patients with IDDM (HbA 1c 8.4±0.2%), who were clinically free of macrovascular disease, and 33 healthy normolipidemic subjects (HbA 1c 5.1±0.1%, P<0.001 vs. IDDM). The groups had comparable serum total-, LDL- (2.9±0.1 vs. 2.8±0.1 mmol/l, IDDM vs. controls), and HDL-cholesterol concentrations. OxLDLab were 1.5-fold higher in the IDDM patients (1.8±0.1) than in the normal subjects (1.2±0.1, P<0.001). OxLDLab were correlated with age in normal subjects, but not with age, duration of disease, LDL-cholesterol, HbA 1c or degree of microvascular complications in patients with IDDM. To determine whether oxLDLab are associated with endothelial dysfunction in vivo, blood flow responses to intrabrachial infusions of acetylcholine, sodium nitroprusside and l-NMMA were determined in 23 of the patients with IDDM (age 33±1 years, body mass index 24.3±0.6 kg/m 2, HbA 1c 8.5±0.3%) and in the 33 matched normal males. OxLDLab were 41% increased in IDDM (1.7±0.2 vs. 1.2±0.1, P<0.01). Within the group of IDDM patients, HbA 1c but not oxLDLab or LDL-cholesterol, was inversely correlated with the forearm blood flow response to acetylcholine ( r=−0.51, P<0.02), an endothelium-dependent vasodilator, but not to sodium nitroprusside ( r=0.06, NS). These data demonstrate that oxLDLab concentrations are increased in patients with IDDM, but show that chronic hyperglycemia rather than oxLDLab, is associated with impaired endothelium-dependent vasodilation in these patients.