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Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease

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 popu...

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Autores principales: Birukov, Anna, Plavša, Branimir, Eichelmann, Fabian, Kuxhaus, Olga, Hoshi, Rosangela Akemi, Rudman, Najda, Štambuk, Tamara, Trbojević-Akmačić, Irena, Schiborn, Catarina, Morze, Jakub, Mihelčić, Matea, Cindrić, Ana, Liu, Yanyan, Demler, Olga, Perola, Markus, Mora, Samia, Schulze, Matthias B., Lauc, Gordan, Wittenbecher, Clemens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9679264/
https://www.ncbi.nlm.nih.gov/pubmed/36174116
http://dx.doi.org/10.2337/dc22-0833
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author Birukov, Anna
Plavša, Branimir
Eichelmann, Fabian
Kuxhaus, Olga
Hoshi, Rosangela Akemi
Rudman, Najda
Štambuk, Tamara
Trbojević-Akmačić, Irena
Schiborn, Catarina
Morze, Jakub
Mihelčić, Matea
Cindrić, Ana
Liu, Yanyan
Demler, Olga
Perola, Markus
Mora, Samia
Schulze, Matthias B.
Lauc, Gordan
Wittenbecher, Clemens
author_facet Birukov, Anna
Plavša, Branimir
Eichelmann, Fabian
Kuxhaus, Olga
Hoshi, Rosangela Akemi
Rudman, Najda
Štambuk, Tamara
Trbojević-Akmačić, Irena
Schiborn, Catarina
Morze, Jakub
Mihelčić, Matea
Cindrić, Ana
Liu, Yanyan
Demler, Olga
Perola, Markus
Mora, Samia
Schulze, Matthias B.
Lauc, Gordan
Wittenbecher, Clemens
author_sort Birukov, Anna
collection PubMed
description 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 chromatography, 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.
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spelling pubmed-96792642023-01-21 Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease Birukov, Anna Plavša, Branimir Eichelmann, Fabian Kuxhaus, Olga Hoshi, Rosangela Akemi Rudman, Najda Štambuk, Tamara Trbojević-Akmačić, Irena Schiborn, Catarina Morze, Jakub Mihelčić, Matea Cindrić, Ana Liu, Yanyan Demler, Olga Perola, Markus Mora, Samia Schulze, Matthias B. Lauc, Gordan Wittenbecher, Clemens Diabetes Care Cardiovascular and Metabolic Risk 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 chromatography, 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. American Diabetes Association 2022-11 2022-10-25 /pmc/articles/PMC9679264/ /pubmed/36174116 http://dx.doi.org/10.2337/dc22-0833 Text en © 2022 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/journals/pages/license.
spellingShingle Cardiovascular and Metabolic Risk
Birukov, Anna
Plavša, Branimir
Eichelmann, Fabian
Kuxhaus, Olga
Hoshi, Rosangela Akemi
Rudman, Najda
Štambuk, Tamara
Trbojević-Akmačić, Irena
Schiborn, Catarina
Morze, Jakub
Mihelčić, Matea
Cindrić, Ana
Liu, Yanyan
Demler, Olga
Perola, Markus
Mora, Samia
Schulze, Matthias B.
Lauc, Gordan
Wittenbecher, Clemens
Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
title Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
title_full Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
title_fullStr Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
title_full_unstemmed Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
title_short Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
title_sort immunoglobulin g n-glycosylation signatures in incident type 2 diabetes and cardiovascular disease
topic Cardiovascular and Metabolic Risk
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9679264/
https://www.ncbi.nlm.nih.gov/pubmed/36174116
http://dx.doi.org/10.2337/dc22-0833
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