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Serum Glycome as a Diagnostic and Prognostic Factor in Gestational Diabetes Mellitus

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Abstract

Gestational diabetes mellitus (GDM) is a risk factor for both mother and fetus/neonate during and after the pregnancy. Inconsistent protocols and cumbersome screening procedures warrant the search for new and easily accessible biomarkers. We investigated a potential of serum N-glycome to differentiate between healthy pregnant women (n = 49) and women with GDM (n = 53) using a lectin-based microarray and studied the correlation between the obtained data and parameters of glucose and lipid metabolism. Four out of 15 lectins used were able to detect the differences between the control and GDM groups in fucosylation, terminal galactose/N-acetylglucosamine (Gal/GlcNAc), presence of Galα1,4Galβ1,4Glc (Gb3 antigen), and terminal α2,3-sialylation with AUC values above 60%. An increase in the Gb3 antigen and α2,3-sialylation correlated positively with GDM, whereas the amount of fucosylated glycans correlated negatively with the content of terminal Gal/GlcNAc. The content of GlcNAc oligomers correlated with the highest number of blood analytes, indices, and demographic characteristics, but failed to discriminate between the groups. The presence of terminal Gal residues correlated positively with the glucose levels and negatively with the LDL levels in the non-GDM group only. The results suggest fucosylation, terminal galactosylation, and the presence of Gb3 antigen as prediction markers of GDM.

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Acknowledgments

We thank B. Wiltschi and R. Pasupuleti from the Austrian Centre of Industrial Biotechnology (ACIB) for the kind gift of Shiga toxin (Stx1B lectin).

Funding

This work was supported by the Ministry of Science, Technological Development, and Innovations of the Republic of Serbia (grant no. 451-03-47/2023-14/200019), Multilateral Scientific and Technological Cooperation in the Danube Region (grant no. 337-00-00322/2019-09/151), Slovak Research and Development Agency (APVV, grant no. DS-FR-19-0034), and Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA, grant no. 2/0120/22).

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    Authors and Affiliations

    1. Department of High-Risk Pregnancies, University Clinic for Gynecology and Obstetrics “Narodni Front”, Belgrade, Serbia

      Ognjen Radojičić, Vesna Mandić Marković & Željko Miković

    2. Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovakia

      Lucia Pažitná, Paras Kundalia, Kristina Kianičková & Jaroslav Katrlík

    3. Department for Metabolism, Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia

      Zorana Dobrijević, Olgica Nedić & Dragana Robajac

    4. Medical School, University of Belgrade, Belgrade, Serbia

      Vesna Mandić Marković & Željko Miković

    Authors
    1. Ognjen Radojičić
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    2. Lucia Pažitná
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    Contributions

    D.R. and Z.D. conceived and supervised the study; O.R., L.P., P.K., K.K., and D.R. carried out experiments; D.R. discussed the results of experiments with input from all authors; D.R. and J.K. wrote the manuscript; Y.D., J.K., V.M.M., Ž.M., and O.N. edited the manuscript.

    Corresponding author

    Correspondence to Dragana Robajac.

    Ethics declarations

    The study was approved by the Ethical Committees of the University Clinic for Gynecology and Obstetrics “Narodni Front” and Institute for the Application of Nuclear Energy (Approval no. 05006-2019-4925). All procedures carried out in the research were in compliance with the ethical standards of the National Research Ethics Committee and with the Helsinki Declaration of 1964 and its subsequent changes and with comparable ethics standards. Informed voluntary consent was obtained from every participant of the study. The authors of this work declare that they have no conflicts of interest.

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    Table S1.

    Lectins used in lectin-based microarray experiments and their carbohydrate specificities

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    Radojičić, O., Pažitná, L., Dobrijević, Z. et al. Serum Glycome as a Diagnostic and Prognostic Factor in Gestational Diabetes Mellitus. Biochemistry Moscow 89, 148–158 (2024). https://doi.org/10.1134/S0006297924010097

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