Search for novel biomarkers for predicting perinatal outcomes in pregnancy complicated by gestational diabetes
A. A. Kutsenko,
A. G. Vasilyeva,
D. R. Melykh,
E. V. Belokorovii,
I. S. Popova,
Yu. G. Birulina,
S. Yu. Yuriev,
V. E. Frankevich https://doi.org/10.15829/1728-8800-2025-4454
EDN: RUUZSZ
Abstract
Aim. To identify new markers using omics technologies for use as predictors of fetal growth and developmental abnormalities in gestational diabetes (GD).
Material and methods. The long-term goal of this study is to create a unique biological sample collection that can be used to assess the risk of diabetic fetopathy (DF) and other adverse perinatal outcomes by identifying early preclinical markers. To achieve this goal, the following studies were planned for the first stage: the formation of a reference collection of biomaterial from women with a known perinatal outcome and its subsequent comprehensive analysis to identify key markers. Conducting complex experiments using genetic, immunological, and mass spectrometric approaches allows for a comprehensive assessment of molecular GD pathogenesis and the identification of complementary biomarkers. For this study, a collection of plasma samples from pregnant women in the first trimester, women in labor, amniotic fluid, and umbilical cord plasma was compiled. The resulting biomaterial samples were frozen and stored at a temperature not exceeding -80 оC. A sample of 100 women aged 18-45 years, at 34 weeks 1 day to 41 weeks 6 days of gestation, from both groups with and without GD, was included in the current study. Enzyme-linked immunosorbent assay (ELISA) was performed on samples for a number of regulatory proteins and embryotropic antibodies, molecular genetic analysis of hemostasis gene polymorphisms, and mass spectrometric analysis of amino acids.
Results. A comparative analysis revealed that pregnant women with GD were more likely to have the FGB 455 G/A fibrinogen gene polymorphism (p=0,008), and their autoimmune antibody profile was altered, consistent with supraphysiological apoptosis and insulin resistance. In the absence of fetal macrosomia, maternal plasma levels of tissue plasminogen activator were lower (p=0,001). The main findings of mass spectrometry of amino acids in the blood of women with GD were lower concentrations of tryptophan (p=0,025) and γ-aminobutyric acid (p=0,023). In amniotic fluid and cord blood in GD, decreased concentrations of amino acids responsible for protein synthesis (lysine and methionine) and increased concentrations of amino acids associated with macrosomia were detected.
Conclusion. The study results confirm metabolic, immune, and hemorheological disturbances in maternal GD, associated with abnormal amino acid composition in cord blood and amniotic fluid in neonates with macrosomia. The identified differences in the metabolome can be considered potential markers for identifying the risk of unfavorable perinatal outcomes.
Supporting agencies: The research was carried out at the expense of the grant of the Russian Science Foundation No. 24-64-00006, http://rscf.ru/project/24-64-00006/
About the Authors
A. A. Kutsenko
Siberian State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Postgraduate of the Department of Obstetrics and Gynecology.
Moskovsky Trakt, 2, Tomsk, 634050
A. G. Vasilyeva
Siberian State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Applicant of the Department of Obstetrics and Gynecology.
Moskovsky Trakt, 2, Tomsk, 634050
D. R. Melykh
Siberian State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Applicant of the Department of Obstetrics and Gynecology.
Moskovsky Trakt, 2, Tomsk, 634050
E. V. Belokorovii
Siberian State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Resident of the Department of Obstetrics and Gynecology.
Moskovsky Trakt, 2, Tomsk, 634050
I. S. Popova
Siberian State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
PhD, Researcher of the central research laboratory.
Moskovsky Trakt, 2, Tomsk, 634050
Yu. G. Birulina
Siberian State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
PhD, Deputy Head of the central research laboratory.
Moskovsky Trakt, 2, Tomsk, 634050
S. Yu. Yuriev
Siberian State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Dr. Sci (Medicine), professor of the Department of Obstetrics and Gynecology.
Moskovsky Trakt, 2, Tomsk, 634050
V. E. Frankevich
V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Dr. Sci (Physics and Mathematics) Head of the Department of Systems Biology in Reproduction Institute of Translational Medicine FSBI National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov Ministry of Health of the Russian Federation.
Akademika Oparina St., 4, Moscow, 117997
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Supplementary files
What is already known about the subject?
- Gestational diabetes (GD) is associated with metabolic, immune, and hemorheological disturbances that affect fetal growth and development.
- Standard diagnostic methods for GD, such as the glucose tolerance test, do not always predict adverse perinatal outcomes, including macrosomia.
What might this study add?
- Significant changes in the metabolome were found in maternal blood, cord blood, and amniotic fluid during pregnancies complicated by GD. These changes include decreased concentrations of amino acids important for the regulation of metabolic processes and inflammatory responses (tryptophan and γ-aminobutyric acid); those important for protein synthesis — lysine and methionine; and an accumulation of branched-chain amino acids, which increase insulin resistance.
- Biobanking of material from the first trimester until delivery will make it possible to assess the possibility of using these metabolites as early markers of macrosomia and diabetic fetopathy.
Review
For citations:
Kutsenko A.A., Vasilyeva A.G., Melykh D.R., Belokorovii E.V., Popova I.S., Birulina Yu.G., Yuriev S.Yu., Frankevich V.E. Search for novel biomarkers for predicting perinatal outcomes in pregnancy complicated by gestational diabetes. Cardiovascular Therapy and Prevention. 2025;24(11):4454. (In Russ.) https://doi.org/10.15829/1728-8800-2025-4454. EDN: RUUZSZ
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