Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
Journal article, 2022
OBJECTIVE N-glycosylation is a functional posttranslational modification of immunoglobulins (Igs). We hypothesized that specific IgG N-glycans are associated with incident type 2 diabetes and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We performed case-cohort studies within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam cohort (2,127 in the type 2 diabetes subcohort [741 incident cases]; 2,175 in the CVD subcohort [417 myocardial infarction and stroke cases]). Relative abundances of 24 IgG N-glycan peaks (IgG-GPs) were measured by ultraperformance liquid chromatog-raphy, and eight glycosylation traits were derived based on structural similarity. End point–associated IgG-GPs were preselected with fractional polynomials, and prospective associations were estimated in confounder-adjusted Cox models. Diabetes risk associations were validated in three independent studies. RESULTS After adjustment for confounders and multiple testing correction, IgG-GP7, IgG-GP8, IgG-GP9, IgG-GP11, and IgG-GP19 were associated with type 2 diabetes risk. A score based on these IgG-GPs was associated with a higher diabetes risk in EPIC-Potsdam and independent validation studies (843 total cases, 3,149 total non-cases, pooled estimate per SD increase 1.50 [95% CI 1.37–1.64]). Associations of IgG-GPs with CVD risk differed between men and women. In women, IgG-GP9 was inversely associated with CVD risk (hazard ratio [HR] per SD 0.80 [95% CI 0.65–0.98]). In men, a weighted score based on IgG-GP19 and IgG-GP23 was associated with higher CVD risk (HR per SD 1.47 [95% CI 1.20–1.80]). In addition, several derived traits were associated with cardiometabolic disease incidence. CONCLUSIONS Selected IgG N-glycans are associated with cardiometabolic risk beyond classic risk factors, including clinical biomarkers.
Author
Anna Birukov
Harvard School of Public Health
Deutsches Zentrum für Diabetesforschung
German Institute of Human Nutrition
Branimir Plavćsa
Sveučilište u Zagrebu, Farmaceutsko Biokemijski Fakultet
Fabian Eichelmann
Deutsches Zentrum für Diabetesforschung
German Institute of Human Nutrition
Olga Kuxhaus
Deutsches Zentrum für Diabetesforschung
German Institute of Human Nutrition
Rosangela Akemi Hoshi
Harvard Medical School
Najda Rudman
Sveučilište u Zagrebu, Farmaceutsko Biokemijski Fakultet
Tamara Stambuk
Genos Ltd
Irena Trbojevićc-Akmaćcićc
Genos Ltd
Catarina Schiborn
German Institute of Human Nutrition
Deutsches Zentrum für Diabetesforschung
Jakub Morze
Harvard School of Public Health
University of Warmia and Mazury in Olsztyn
Matea Mihelćcićc
Genos Ltd
Ana Cindrićc
Genos Ltd
Yanyan Liu
Harvard Medical School
Olga Demler
Harvard Medical School
Swiss Federal Institute of Technology in Zürich (ETH)
Markus Perola
Finnish Institute for Health and Welfare
University of Helsinki
Samia Mora
Harvard Medical School
Matthias B. Schulze
German Institute of Human Nutrition
Deutsches Zentrum für Diabetesforschung
University of Potsdam
Gordan Lauc
Genos Ltd
Sveučilište u Zagrebu, Farmaceutsko Biokemijski Fakultet
Clemens Wittenbecher
German Institute of Human Nutrition
Harvard School of Public Health
Chalmers, Biology and Biological Engineering, Food and Nutrition Science
Diabetes Care
0149-5992 (ISSN) 19355548 (eISSN)
Vol. 45 11 2729-2736Subject Categories
Endocrinology and Diabetes
General Practice
Nutrition and Dietetics
DOI
10.2337/dc22-0833
PubMed
36174116