Associations between autoantibodies against apolipoprotein B-100 peptides and vascular complications in patients with type 2 diabetes

G N Fredrikson, D V Anand, D Hopkins, R Corder, R Alm, E Bengtsson, P K Shah, A Lahiri, J Nilsson, G N Fredrikson, D V Anand, D Hopkins, R Corder, R Alm, E Bengtsson, P K Shah, A Lahiri, J Nilsson

Abstract

Aims/hypothesis: Oxidation of LDL in the arterial extracellular matrix is a key event in the development of atherosclerosis and autoantibodies against oxidised LDL antigens reflect disease severity and the risk of developing acute cardiovascular events. Since type 2 diabetes is associated with increased oxidative stress, we tested the hypothesis that autoantibodies against oxidised LDL antigens are biomarkers for vascular complications in diabetes.

Methods: We studied 497 patients with type 2 diabetes without clinical signs of coronary heart disease. Oxidised LDL autoantibodies were determined by ELISA detecting IgG and IgM specific for native and malondialdehyde (MDA)-modified apolipoprotein B-100 peptides p45 and p210. The severity of coronary disease was assessed as the coronary artery calcium score.

Results: Patients affected by retinopathy had significantly higher levels of IgG against MDA-p45 and MDA-p210. In contrast, high levels of autoantibodies against the corresponding native peptides were associated with less coronary calcification and a lower risk of progression of coronary disease.

Conclusions/interpretation: Our observations suggest that LDL oxidation is involved in the pathogenesis of diabetic retinopathy and that autoantibodies against apolipoprotein B peptides may act as biomarkers for both micro- and macrovascular complications in diabetes.

Figures

Fig. 1
Fig. 1
Box plots showing plasma levels (absorbance [abs] units measured at 405 nm) of a IgG and b IgM against native and MDA-modified ApoB peptides p45 and p210 in the study cohort
Fig. 2
Fig. 2
Box plots showing plasma levels of IgG (absorbance [abs] units measured at 405 nm) against a native p45, b MDA-p45, c native p210 and d MDA-p210 in diabetic individuals with and without retinopathy. †p < 0.1, *p < 0.05, **p < 0.01, ***p < 0.001
Fig. 3
Fig. 3
Box plots showing plasma levels of a IgG against (absorbance [abs] units measured at 405 nm) native p45, b IgM against native p45, c IgG against native p210 and d IgM against native p210 in diabetic individuals with low to moderate (≤400 Agatston units) and severe to extensive (>400 Agatston units) coronary calcification. *p < 0.05, **p < 0.01, ‡p = 0.005

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