Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
Artikel i vetenskaplig tidskrift, 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.
Författare
Anna Birukov
Deutsches Zentrum für Diabetesforschung
Harvard School of Public Health
Deutsches Institut für Ernährungsforschung
Branimir Plavćsa
Sveučilište u Zagrebu, Farmaceutsko Biokemijski Fakultet
Fabian Eichelmann
Deutsches Zentrum für Diabetesforschung
Deutsches Institut für Ernährungsforschung
Olga Kuxhaus
Deutsches Institut für Ernährungsforschung
Deutsches Zentrum für Diabetesforschung
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
Deutsches Zentrum für Diabetesforschung
Deutsches Institut für Ernährungsforschung
Jakub Morze
University of Warmia and Mazury in Olsztyn
Harvard School of Public Health
Matea Mihelćcićc
Genos Ltd
Ana Cindrićc
Genos Ltd
Yanyan Liu
Harvard Medical School
Olga Demler
Harvard Medical School
Eidgenössische Technische Hochschule Zürich (ETH)
Markus Perola
Helsingin Yliopisto
Finnish Institute for Health and Welfare
Samia Mora
Harvard Medical School
Matthias B. Schulze
Deutsches Institut für Ernährungsforschung
Universität Potsdam
Deutsches Zentrum für Diabetesforschung
Gordan Lauc
Genos Ltd
Sveučilište u Zagrebu, Farmaceutsko Biokemijski Fakultet
Clemens Wittenbecher
Harvard School of Public Health
Chalmers, Biologi och bioteknik, Livsmedelsvetenskap
Deutsches Institut für Ernährungsforschung
Diabetes Care
0149-5992 (ISSN) 19355548 (eISSN)
Vol. 45 11 2729-2736Ämneskategorier (SSIF 2011)
Endokrinologi och diabetes
Allmänmedicin
Näringslära
DOI
10.2337/dc22-0833
PubMed
36174116