Soluble LDL-immune complexes in type 2 diabetes and vascular disease.
OBJECTIVE
The oxidative modification of LDL has been shown to affect its clearance and to exert cytotoxic and immunogenic effects. The objective of our study was to analyse markers of LDL oxidation-soluble LDL containing immune complexes (LDL-ICs) in type 2 diabetes with micro- and macrovascular disease.


METHODS
The study included 69 diabetic patients with coronary artery disease (DM + CAD), 78 non-diabetics with CAD, 47 controls, and 27 diabetics with nephropathy and 36 free from complications. OxLDL antibodies and advanced glycated end-products were measured by ELISA, and LDL-IC apo B content after PEG precipitation.


RESULTS
Determination of a broad range of oxLDL antibody activity in all study groups showed no significant differences. In contrast, the content of apo B, a component of the antigen moiety of oxLDL-ICs, was higher in CAD and diabetes (+ CAD) than in LDL-ICs isolated from controls (p < 0.001). LDL-ICs did not differ between patients with CAD + DM and CAD patients free from diabetes. LDL-IC levels in diabetic patients with or without microangiopathy were significantly higher than in healthy volunteers (PEG-apo B 0.278 +/- 0.107 vs. 0.165 +/- 105 g/l, p < 0.002; PEG-IgG 151.7 +/- 76 vs. 115.4 +/- 62 g/l, p < 0.05). However, there was no significant difference in the level of circulating LDL-ICs between the subgroup of diabetic patients with nephropathy/retinopathy and patients free of microvascular disease (Ab-oxLDL 27.7 +/- 10.4 vs. 27.1 +/- 9.3 AU, NS; PEG-apo B 0.324 +/- 0.111 vs. 0.287 +/- 0.124 g/l, NS; PEG-IgG 1.68 +/- 0.68 vs. 1.42 +/- 0.80 g/l, NS). There was a statistically significant positive correlation between AGE content and LDL-ICs (r = 0.35, p < 0.009). A significant but inverse correlation was recorded between triglyceride concentration and level of LDL-ICs in DM + CAD (r = - 0.32, p < 0.016) and CAD patients (r = - 0.35, p < 0.002). A highly significant negative correlation between triglycerides and circulating LDL-ICs (r = - 0.54, p < 0.039) was observed in patients with early nephropathy, but not in those with physiological proteinuria. It is known that at a high triglyceride level in type 2 diabetes, the majority of LDL are small and dense, thus being more susceptible to oxidative modification. This could be a possible mechanism explaining why more LDL-ICs, with a level inversely correlating with triglyceride concentration, are generated in diabetes.


CONCLUSIONS
The increased level of circulating LDL-ICs is a risk factor for the general population, including those with diabetes. Our results suggested the contribution of LDL-ICs to the development of atherosclerosis to probably be more significant than the direct contribution of oxLDLAb itself.
Turk
Z
Z
Vuk Vrhovac University Clinic for Diabetes, Dugi dol 4A, 10000 Zagreb, Croatia.zturk@idb.hr
Sesto
M
M
Skodlar
J
J
Ferencak
G
G
Turk
N
N
Stavljenić-Rukavina
A
A
D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism*; D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism; D003324:Coronary Artery Disease / Q000276:immunology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D000936:Antigen-Antibody Complex; D001055:Apolipoproteins B; D001323:Autoantibodies; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein