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Abstract
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 N-glycosylation 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.
- IgG N-glycans
- diabetes type 2
- N-glycosylation
- kidney function
- nephropathy
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Footnotes
Contributors SSS maintained the DiaGene study database, analyzed the data, wrote and reviewed/edited the manuscript. RH, CKEM analyzed and completed the database, wrote and reviewed/edited manuscript. AGL collected and designed the DiaGene Study, reviewed and edited the manuscript. OG, GL reviewed and edited the manuscript. EJGS collected and designed the DiaGene Study, reviewed and edited the manuscript. MvH coordinated the analyses; initiated the research question, collection and design of the DiaGene study; wrote/reviewed and edited the manuscript. All authors have read and approved the final manuscript. MvH is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was approved by the Medical Ethical Committees of the Erasmus MC, Catharina Hospital and the Maxima Medical Center (MEC-230).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement The datasets generated during and/or analyzed during the current study are not publicly available. The raw data are subject to “Special Categories of Personal Data (Sensitive Data)” (GDPR, Article 9); therefore, raw data sharing is not in line with the privacy principles. Also, the information provided to the participants in the study states that the individual data are only accessible to the researchers, the ethical review board and (local) authorities. The informed consent given by the participants is therefore not sufficient for open access publication of indirectly identifiable data. Datasets are available from the corresponding author on reasonable request.