Associations between plasma protein, IgG and IgA N-glycosylation and metabolic health markers in pregnancy and gestational diabetes

Abstract Background. Monitoring of the human circulating N-glycome could provide valuable insight into an individual’s metabolic status. Therefore, we examined if aberrant carbohydrate metabolism in gestational diabetes mellitus (GDM) associates with alterations in plasma protein, immunoglobulin G (IgG) and immunoglobulin A (IgA) N-glycosylation.Methods. Plasma protein, IgG and IgA N-glycans were enzymatically released, purified and chromatographically profiled in 48 pregnant women with normal glucose tolerance and 41 pregnant women with GDM, all sampled at 24-28 weeks of gestation.Results. Fasting insulin exhibited significant associations to numerous glycan traits, including several plasma protein N-glycans bearing bisecting GlcNAc, afucosylated fully sialylated IgG glycan and fully sialylated triantennary IgA glycan (padj range: 7.66x10-05–1.15x10-02). Insulin resistance markers HOMA2-IR and HOMA2-%B were mostly associated to the same glycan structures as fasting insulin. Both markers also showed positive association with high-branched plasma glycans (padj=1.15x10-02 and 2.26x10-03) and negative association with low-branched plasma glycans (padj=1.25x10-02 and 2.27x10-03). Additionally, HOMA2-%B index was significantly related to the glycosylation features describing IgG sialylation. Multiple glycans showed significant associations with total cholesterol and triglyceride levels. None of the tested glycan traits showed a significant difference between GDM and normoglycemic pregnancies.Conclusion. Markers of glucose homeostasis and lipid metabolism in pregnancy show extensive associations to various N-glycosylation features. However, plasma protein, IgG and IgA N-glycans were not able to differentiate pregnant women with and without GDM, possibly due to numerous physiological changes accompanying pregnancy, which confound the impact of GDM on protein glycosylation.