IgG N-Glycosylation and Incident Neuropathy and Nephropathy in People With Type 2 Diabetes: A Pooled Analysis of Prospective Cohort Studies

Abstract

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.