Potential Glycobiomarkers in Maternal Obesity and Gestational Diabetes During Human Pregnancy

J Clin Med. 2025 Feb 27;14(5):1626. doi: 10.3390/jcm14051626.

Abstract

Introduction: Obesity is a rapidly growing common health problem worldwide that can lead to the development of gestational diabetes mellitus (GDM). However, GDM not only affects women with obesity but can also develop at any time, even after the OGTT test; therefore, an increasing number of complications related to GDM can be seen in both mothers and their children. It is necessary to discover biomarkers capable of indicating the development of GDM or complications during/after pregnancy. Since the N-glycosylation motif of human IgG has been described to change under many physiological and pathological conditions, it is a promising target for biomarker research. In our study, the effects of obesity and GDM were investigated on human serum IgG N-linked glycosylation patterns during human pregnancy. Materials and Methods: The study participants were categorized into four groups according to their body mass index (BMI) and GDM status: normal weight as control, obese (BMI > 30 kg/m2), normal weight with GDM, and obese with GDM. The released N-glycan components of IgG were separated with capillary electrophoresis and detected using a laser-induced fluorescence detector. Results: The result revealed several differences between the N-glycosylation patterns of the four study groups. Of this, 17 of the 20 identified structures differed significantly between the groups. The ratios of sialylated to non-sialylated structures were not changed significantly, but the core fucosylation level showed a significant decrease in the GDM and obese GDM groups compared to the control subjects. The lowest degree of core fucosylation was observed in the GDM group. Conclusions: The findings indicate that obesity in isolation does not have a significant impact on the IgG N-glycosylation pattern in pregnancy. Conversely, alterations in the N-glycan profile of antibodies may serve as biomarkers for the diagnosis of GDM in mothers with a normal BMI, although more evidence is needed. By incorporating glycan-based biomarkers into clinical practice, healthcare providers can improve early detection, personalize management strategies, and potentially mitigate adverse pregnancy outcomes associated with obesity and GDM.

Keywords: capillary electrophoresis; gestational diabetes mellitus; human IgG N-glycome; maternal obesity; molecular diagnostics.

Grants and funding

This work was supported by the University of Szeged, Albert Szentgyörgyi Medical School, Faculty Research Grant, ‘Géza Hetényi’ Fund [No.:5S 724 (A202)], ‘Bohdan Malaniak CSMC—RECOOP Young Scientists Research Grant BMYS 2019–2020 Farkas—Guttman #008 Modification of IgG-glycosylation and plasma N-glycome related to obesity during pregnancy and by the University of Debrecen Program for Scientific Publication PTP2025. This is contribution #219 of the Horváth Csaba Memorial Laboratory of Bioseparation Sciences.