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Autoantibodies Against Methylglyoxal-Modified Apolipoprotein B100 and ApoB100 Peptide Are Associated With Less Coronary Artery Atherosclerosis and Retinopathy in Long-Term Type 1 Diabetes

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posted on 15.04.2021, 18:08 by Kari Anne Sveen, Kristine Bech Holte, Mona Svanteson, Kristian F Hanssen, Jan Nilsson, Eva Bengtsson, Tore Julsrud Berg
Objectives: Methylglyoxal (MGO), a reactive aldehyde forming advanced glycation end products (AGEs), is increased in diabetes and recognized by the immune system, resulting in anti-AGE-specific autoantibodies. The association of these immune responses with macro-and microvascular complications in type 1 diabetes remains unclarified. We investigated associations between MGO-modified ApoB100 and ApoB100 peptide (MGO-p5) autoantibodies and coronary atherosclerosis and retinopathy in type 1 diabetes.

Research Design and Methods: IgM and IgG against MGO-apoB100 and MGO-p5 were measured by ELISA in plasma from 103 type 1 diabetessubjects and 63 controls (Dialong study) and in a replication cohort of 27 type 1 diabetes subjects (Oslo study). Coronary atherosclerosis was assessed by computer tomography coronary angiography or intravascular ultrasound. Retinopathy was classified by retinal photos.

Results: MGO-ApoB100 IgM and MGO-p5 IgM levels were higher in diabetes subjects with no coronary artery stenosis compared to subjects with significant stenosis (median (IQR): 96.2 AU (71-126.8) vs. 54 AU (36.1-85.4), p=0.003 for MGO-ApoB100, and 77.4 AU (58-106) vs 36.9 AU (28.9-57.4), p=0.005 for MGO-p5). MGO-ApoB100 IgM and MGO-p5 IgM were associated with less severe coronary stenosis after adjusting for confounders (odds ratio (95% CI): 0.2 (0.05-0.6), p=0.01 and 0.22 (0.06-0.75), p=0.02. The inverse association of MGO-p5 IgM and coronary stenosis was confirmed in the replication cohort. Subjects with proliferative retinopathy had significantly lower MGO-ApoB100 IgM and MGO-p5 IgM than those with background retinopathy.

Conclusions: Autoantibodies against AGE-modified apoB100 are inversely associated with coronary atherosclerosis and proliferative retinopathy, suggesting vascular protective effects of these autoantibodies in type 1 diabetes.

Funding

The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement n° 609020 - Scientia Fellows, Oslo Diabetes Research Centre, the Norwegian Diabetics’ Centre, the Swedish Heart and Lung foundation, Lund University Diabetes Center (Swedish Research Council - Strategic Research Area Exodiab Dnr 2009-1039, Linnaeus grant Dnr 349-2006-23 and the Swedish Foundation for Strategic Research Dnr IRC15-006), Lund University Diabetes Center, Crafoord foundation, and Albert Påhlsson foundation.

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