title: Autoantibodies to oxidised low density lipoproteins in IDDM are inversely related to metabolic control and microvascular complications.
abstract: Diabetes mellitus is associated with an increased risk of atherosclerosis. The oxidation of low-density lipoproteins (LDL) is considered a key event in the initiation of atherosclerosis. To investigate LDL oxidation in vivo we measured autoantibodies to oxidised LDL (oxLDL) in 94 patients with insulin-dependent diabetes mellitus (IDDM), compared to 27 age-matched, healthy control subjects. Patients and control subjects were screened for autoantibodies using a solid phase ELISA, comparing the binding to oxLDL with that to native LDL (nLDL). In patients with IDDM the oxLDL/nLDL antibody ratio was significantly higher than in control subjects (means+/-SEM: 2.24+/-0.26 vs 1.17+/-0.17, p < 0.03). Antibody-negative patients had a longer diabetes duration (13.5+/-1.3 vs 9.1+/-1.1 years, p < 0.01) and higher actual and mean HbA1c levels compared to antibody-positive patients (8.8+/-0.2 vs 7.9+/-0.2%, p < 0.005 and 8.3+/-0.2 vs 7.7+/-0.2%, p < 0.03; respectively). In patients with a high microangiopathy score, the antibody ratio was lower than in patients without complications (1.04+/-0.10 vs 2.40+/-0.29, p < 0.01). OxLDL specific immune complexes were found exclusively in antibody-negative as compared to antibody-positive patients (18.3 vs 0 %; p < 0.01). Our data demonstrate an inverse relationship between free oxLDL antibodies and the severity of the disease. This apparent paradox can be explained in part by our demonstration of oxLDL immune complexes, masking free antibodies.
authors.affiliation: Department of Medicine 1, Rudolfstiftung Hospital, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Festa
authors.forename: H P
authors.initials: HP
authors.lastname: Kopp
authors.forename: G
authors.initials: G
authors.lastname: Schernthaner
authors.forename: E J
authors.initials: EJ
authors.lastname: Menzel
mesh_terms: D000328:Adult; D000367:Age Factors; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D016022:Case-Control Studies; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005968:Glutamate Decarboxylase / Q000032:analysis / Q000276:immunology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D010084:Oxidation-Reduction; D011485:Protein Binding; D013997:Time Factors; D014652:Vascular Diseases / Q000150:complications / Q000276:immunology / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015922:Complement C1q; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein