Introduction Inflammatory processes are thought to be involved in kidney function decline in individuals with type 2 diabetes. Glycosylation of immunoglobulin G (IgG) is an important post-translation process affecting the inflammatory potential of IgG. We investigated the prospective relationship between IgG N-glycosylation patterns and kidney function in type 2 diabetes. Research design and methods In the DiaGene study, an all-lines-of-care case–control study (n=1886) with mean prospective follow-up of 7.0 years, the association between 58 IgG N-glycan profiles and estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) per year and during total follow-up was analyzed. Models were adjusted for clinical variables and multiple comparisons. Results Eleven traits were significantly associated with eGFR change per year. Bisecting GlcNAc in fucosylated and fucosylated disialylated structures and monosialylation of fucosylated digalactosylated structures were associated with a faster decrease of eGFR. Fucosylation of neutral and monogalactosylated structures was associated with less eGFR decline per year. No significant associations between IgG glycans and ACR were found. Conclusions In type 2 diabetes, we found IgG Nglycosylation patterns associated with a faster decline of kidney function, reflecting a pro-inflammatory state of IgG. eGFR, but not ACR, was associated with IgG glycans, which suggests these associations may represent renal macroangiopathy rather than microvascular disease.

Additional Metadata
Persistent URL dx.doi.org/10.1136/bmjdrc-2019-001026, hdl.handle.net/1765/128588
Journal Bmj Open Diabetes Research & Care
Organisation Department of Internal Medicine
Citation
Singh, S.S., Heijmans, R., Meulen, C.K.E., Lieverse, A.G, Gornik, O., Sijbrands, E.J.G, … van Hoek, M. (2020). Association of the IgG N-glycome with the course of kidney function in type 2 diabetes. Bmj Open Diabetes Research & Care, 8(1). doi:10.1136/bmjdrc-2019-001026