IgG N-Glycosylation and Incident Neuropathy and Nephropathy in People With Type 2 Diabetes: A Pooled Analysis of Prospective Cohort Studies
Journal article, 2026
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.
Author
Cecilia Martinez Escobedo
Chalmers, Life Sciences, Food and Nutrition Science
Anna Birukov
Harvard School of Public Health
German Institute of Human Nutrition
Ralph Heijmans
Erasmus University Rotterdam
Olga Kuxhaus
German Institute of Human Nutrition
Center for Diabetes Research (DZD)
Fabian Eichelmann
Center for Diabetes Research (DZD)
German Institute of Human Nutrition
Roderick C. Slieker
Leiden University
University of Amsterdam
Elham Memarian
Leiden University
Nina Simunic-Briski
Genos
Femke Rutters
University of Amsterdam
Marieke T. Blom
Amsterdam Public Health Research Institute
University of Amsterdam
Marta Riera
Hospital del Mar Medical Research Institute
Marta Crespo
Hospital del Mar Medical Research Institute
Manfred Wuhrer
Leiden University
Clara Barrios
Hospital del Mar Medical Research Institute
Mandy van Hoek
Erasmus University Rotterdam
Leen M. 't Hart
Leiden University
University of Amsterdam
Eric Sijbrands
Erasmus University Rotterdam
Gordan Lauc
University of Zagreb
Genos
Matthias B. Schulze
University of Potsdam
Center for Diabetes Research (DZD)
German Institute of Human Nutrition
Clemens Wittenbecher
Chalmers, Life Sciences, Food and Nutrition Science
Diabetes Care
0149-5992 (ISSN) 19355548 (eISSN)
Vol. 49 9 1714-1719Subject Categories (SSIF 2025)
Endocrinology and Diabetes
DOI
10.2337/dc26-0620
PubMed
42467059