IgG N-Glycosylation and Incident Neuropathy and Nephropathy in People With Type 2 Diabetes: A Pooled Analysis of Prospective Cohort Studies
OBJECTIVE: To examine whether IgG N-glycosylation patterns are prospectively associated with incident diabetic nephropathy and neuropathy. RESEARCH DESIGN AND METHODS: We analyzed IgG N-glycosylation profiles in four cohorts: EPIC-Potsdam, DiaGene, GenoDiabMar, and Hoorn DCS. Among 3,263 individuals with and without type 2 diabetes at profiling, 674 incident neuropathy and 639 incident nephropathy cases occurred after diabetes diagnosis. Associations of IgG N-glycan peaks (IgG-GPs) and traits with incident outcomes were examined using Cox models and meta-analyzed across cohorts. RESULTS: Agalactosylated, asialylated, and bisected IgG-GPs were associated with higher nephropathy risk (IgG-GP3: hazard ratio [HR] 1.13 [95% CI 1.04-1.24]; IgG-GP4: HR 1.15 [95% CI 1.05-1.26]), while galactosylated and sialylated IgG-GPs were associated with lower risk (IgG-GP14: HR 0.86 [95% CI 0.78-0.94]; IgG-GP18: HR 0.85 [95% CI 0.77-0.94]) (all false discovery rate <0.05). Associations of IgG-GPs with incident neuropathy were rendered nonsignificant after multiple testing correction. CONCLUSIONS: IgG N-glycosylation may reflect immune-related mechanisms relevant to diabetic nephropathy; but the evidence between IgG-GPs and diabetic neuropathy remains inconclusive.
Authors
- Olga Kuxhaus
- Nina Šimunić-Briški
- Mandy van Hoek (ORCID: https://orcid.org/0000-0002-2957-5436)
- Femke Rutters (ORCID: https://orcid.org/0000-0002-1008-678X)
- Leen M. ‘t Hart (ORCID: https://orcid.org/0000-0003-4401-2938)
- Ralph Heijmans
- Marta Riera (ORCID: https://orcid.org/0000-0003-4362-7965)
- Roderick C. Slieker (ORCID: https://orcid.org/0000-0003-0961-9152)
- Matthias Bernd Schulze (ORCID: https://orcid.org/0000-0002-0830-5277)
- Fabian Eichelmann (ORCID: https://orcid.org/0000-0002-3975-5596)
- Clemens Wittenbecher (ORCID: https://orcid.org/0000-0001-7792-877X)
- Anna Birukov (ORCID: https://orcid.org/0000-0002-8306-3351)
- Elham Memarian (ORCID: https://orcid.org/0000-0001-5862-4375)
- Eric J.G. Sijbrands (ORCID: https://orcid.org/0000-0001-8857-7389)
- Clara Barrios
- Cecilia Martinez Escobedo1
- Gordan Lauc
- Marieke T. Blom
- Manfred Wuhrer
- Marta Crespo
Institutions
- Harvard University (US)
- University of Potsdam (DE)
- University of Zagreb (HR)
- Leiden University Medical Center (NL)
- Erasmus MC (NL)
- Netherlands Metabolomics Centre (NL)
- Hospital Del Mar (ES)
- Science Research Laboratory (US)
- Public Health Service of Amsterdam (NL)
- Amsterdam University Medical Centers (NL)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- German Institute of Human Nutrition (DE)
- Heinrich Heine University Düsseldorf (DE)
- Chalmers University of Technology (SE)
- Vrije Universiteit Amsterdam (NL)
- University of Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Publication Details
- Journal
- Diabetes Care
- Published
- 2026-07-17
- DOI
- https://doi.org/10.2337/dc26-0620
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Vetenskapsrådet
- Deutsche Krebshilfe
- Instituto de Salud Carlos III