Diabetes care · 2026
IgG N-Glycosylation and Incident Neuropathy and Nephropathy in People With Type 2 Diabetes: A Pooled Analysis of Prospective Cohort Studies.
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Martinez Escobedo Cecilia, Birukov Anna, Heijmans Ralph, Kuxhaus Olga, Eichelmann Fabian, Slieker Roderick C, Memarian Elham, Simunic-Briski Nina, Rutters Femke, Blom Marieke T, Riera Marta, Crespo Marta, Wuhrer Manfred, Barrios Clara, van Hoek Mandy, 't Hart Leen M, Sijbrands Eric, Lauc Gordan, Schulze Matthias B, Wittenbecher Clemens
Аннотация
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.
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.