Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Autoantibodies against methylglyoxal-modified apolipoprotein B100 and apob100 peptide are associated with less coronary artery atherosclerosis and retinopathy in long-term type 1 diabetes

Sveen, Kari Anne LU ; Holte, Kristine Bech ; Svanteson, Mona ; Hanssen, Kristian F. ; Nilsson, Jan LU ; Bengtsson, Eva LU orcid and Berg, Tore Julsrud (2021) In Diabetes Care 44(6). p.1402-1409
Abstract

OBJECTIVE 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 apolipoprotein B100 (apoB100) and apoB100 peptide 5 (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 subjects with type 1 diabetes and 63 control subjects (Dialong study) and in a replication cohort of 27... (More)

OBJECTIVE 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 apolipoprotein B100 (apoB100) and apoB100 peptide 5 (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 subjects with type 1 diabetes and 63 control subjects (Dialong study) and in a replication cohort of 27 subjects with type 1 diabetes (Oslo study). Coronary atherosclerosis was assessed by computed tomography coronary angiography or intravascular ultrasound. Retinopathy was classified by retinal photos. RESULTS MGO-apoB100 IgM and MGO-p5 IgM levels were higher in subjects with diabetes with no coronary artery stenosis compared with subjects with significant stenosis (median [interquartile range]: 96.2 arbitrary units [AU] [71-126.8] vs. 54 AU [36.1-85.4], P 5 0.003 for MGO-apoB100; and 77.4 AU [58-106] vs. 36.9 AU [28.9-57.4], P 5 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 0.2 [95% CI 0.05-0.6], P 5 0.01; and 0.22 [0.06-0.75], P 5 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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
44
issue
6
pages
1402 - 1409
publisher
American Diabetes Association
external identifiers
  • pmid:33858856
  • scopus:85115657001
ISSN
0149-5992
DOI
10.2337/dc20-2089
language
English
LU publication?
yes
additional info
Funding Information: The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7- PEOPLE-2013-COFUND) under grant agreement 609020 (Scientia Fellows), Oslo Diabetes Research Centre, the Norwegian Diabetes Centre, the Swedish Heart-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), Crafoordska Stiftelsen, and Direkt?r Albert P?hlssons Stiftelse. Funding Information: Acknowledgments. The authors thank Jeni-fer Vallejo and Fong To at Clinical Research Centre, Malmo€, Sweden, for laboratory assistance; Anne Karin Molvær, research nurse, and the staff at Norwegian Diabetes Centre for administrative help; Dag Fosmark (Oslo University Hospital) for analyzing the fundus photos; Professor Knut Dahl-Jørgensen (University of Oslo, Oslo University Hospital, Oslo Diabetes Research Center) for enthusiastic support during the years; and all of the participants in the study. Funding. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement 609020 (Scientia Fellows), Oslo Diabetes Research Centre, the Norwegian Diabetes Centre, the Swedish Heart-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), Crafoordska Stiftelsen, and Direkto€r Albert Påhls-sons Stiftelse. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. K.A.S., E.B., and T.J.B. designed this substudy of the Dialong study. K.A.S. wrote the initial draft of the manuscript with assistance from E.B. and T.J.B. and conducted all analyses. K.B.H., M.S., K.F.H., and J.N. critically reviewed and edited the manuscript. K.A.S. is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. This study was presented in abstract form at the 55th Annual Meeting of the European Association for the Study of Diabetes, Barcelona, Spain, 16–20 September 2019. Publisher Copyright: © 2021 by the American Diabetes Association.
id
1b5e8b39-c6ef-48fe-9b3e-e93ab2f38199
date added to LUP
2021-10-13 10:59:31
date last changed
2024-04-20 13:08:55
@article{1b5e8b39-c6ef-48fe-9b3e-e93ab2f38199,
  abstract     = {{<p>OBJECTIVE 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 apolipoprotein B100 (apoB100) and apoB100 peptide 5 (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 subjects with type 1 diabetes and 63 control subjects (Dialong study) and in a replication cohort of 27 subjects with type 1 diabetes (Oslo study). Coronary atherosclerosis was assessed by computed tomography coronary angiography or intravascular ultrasound. Retinopathy was classified by retinal photos. RESULTS MGO-apoB100 IgM and MGO-p5 IgM levels were higher in subjects with diabetes with no coronary artery stenosis compared with subjects with significant stenosis (median [interquartile range]: 96.2 arbitrary units [AU] [71-126.8] vs. 54 AU [36.1-85.4], P 5 0.003 for MGO-apoB100; and 77.4 AU [58-106] vs. 36.9 AU [28.9-57.4], P 5 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 0.2 [95% CI 0.05-0.6], P 5 0.01; and 0.22 [0.06-0.75], P 5 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.</p>}},
  author       = {{Sveen, Kari Anne and Holte, Kristine Bech and Svanteson, Mona and Hanssen, Kristian F. and Nilsson, Jan and Bengtsson, Eva and Berg, Tore Julsrud}},
  issn         = {{0149-5992}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1402--1409}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{Autoantibodies against methylglyoxal-modified apolipoprotein B100 and apob100 peptide are associated with less coronary artery atherosclerosis and retinopathy in long-term type 1 diabetes}},
  url          = {{http://dx.doi.org/10.2337/dc20-2089}},
  doi          = {{10.2337/dc20-2089}},
  volume       = {{44}},
  year         = {{2021}},
}