Autoantibodies against oxidized LDL and endothelium-dependent vasodilationin insulin-dependent diabetes mellitus

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 antibod ies against oxidized vs. native LDL, oxLDLab) were determined in 38 patient s with IDDM (HbA(1c) 8.4 +/- 0.2%), who were clinically free of macrovascul ar disease, and 33 healthy normolipidemic subjects (HbA,, 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 concentrat ions. 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 wi th age in normal subjects, but not with age, duration of disease, LDL-chole sterol, HbA,, or degree of microvascular complications in patients with IDD M. 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 p atients, HbA(1c) but not oxLDLab or LDL-cholesterol, was inversely correlat ed 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 incr eased in patients with IDDM, but show that chronic hyperglycemia rather tha n oxLDLab, is associated with impaired endothelium-dependent vasodilation i n these patients. (C) 1999 Elsevier Science Ireland Ltd. All rights reserve d.