The role of plasma extracellular vesicles as predictors of gestational diabetes mellitus in the first trimester of pregnancy


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Abstract

Objective: To investigate the composition and concentration of plasma extracellular vesicles (ECVs) in the f irst trimester of pregnancy, and assess their potential as an early predictor of gestational diabetes mellitus (GDM). Materials and methods: The prospective study enrolled 45 pregnant women aged 24 to 42 years managed at the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia. The patients were divided into two groups categorized by pregnancy outcome. Group I (study group) included pregnant women with GDM (n=20), Group II (control group) included pregnant women with normoglycemia (n=25). Group I inclusion criteria were single pregnancy and GDM conf irmed by oral glucose tolerance test (OGTT). The inclusion criteria for Group II were singleton pregnancy with normal OGTT results. All patients gave their informed consent to participate in the study. The criteria for not including patients were multiple pregnancies, chromosomal abnormalities, type 1 and 2 diabetes mellitus, autoimmune diseases, cancer, and congenital fetal malformations. Venous blood samples were taken at 11-14 weeks of pregnancy. Extracellular vesicles were isolated from plasma by centrifugation. The linear size and the number of extracellular vesicles were measured by nanoparticle tracking analysis (NTA). Results: NTA showed that the mean size of the extracellular vesicles was almost identical [92 (85, 103) nm in the study group and 92 (84, 101) nm in the control group]. However, the concentration of ECVs was signif icantly higher in patients who subsequently developed GDM. The likelihood of developing GDM based on ECV concentration was evaluated using receiver operating characteristics (ROC) analysis. The area under the ROC curve was 0.813±0.080 with 95% CI: 0.657-0.970. The resulting model was statistically significant (p=0.003). The optimal cut-off value of ECV concentration corresponding to the highest value of the Youden’s index was 3.224×1011 parts/ ml. The development of GDM was predicted at ECVs concentrations above or equal to this value. The sensitivity and specificity of the model were 80.0% and 66.7%, respectively. Conclusion: The study f indings suggest new possibilities for early prediction of GDM by studying the concentration of extracellular vesicles.

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About the authors

Zulfiya S. Khodzhaeva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Dr. Med. Sci., Professor, Deputy Director for Research, Institute of Obstetrics

Maria E. Abramova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: m_abramova@oparina4.ru
graduate student at the High Risk Pregnancy Department

Kamilla T. Muminova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: k_muminova@oparina4.ru
Ph.D., Researcher of 1st Department of Obstetric Pathology of Pregnancy

Kseniia A. Gorina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: k_gorina@oparina4.ru
PhD, Researcher at the High Risk Pregnancy Department

Ekaterina R. Frolova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: kattirella@gmail.com
graduate student at the High Risk Pregnancy Department

Kirill V. Goryunov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: k_gorunov@oparina4.ru
PhD, Researcher at the Department of Cell Technologies

Denis N. Silachev

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: d_silachev@oparina4.ru
PhD (Bio), Head of the Department of Cell Technologies

Yulia A. Shevtsova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: yu_shevtsova@oparina4.ru
Junior Researcher at the Department of Cell Technologies

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