Factors of energy metabolism in fetal growth restriction

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Objective: This study aimed to was to investigate the blood plasma factors associated with energy metabolism in pregnant women with fetal growth restriction (FGR) and to evaluate their diagnostic performance.

Materials and methods: This cohort study involved 59 pregnant women. The study group (n=30) comprised patients diagnosed with FGR confirmed after childbirth. The control group (n=29) included women with normal pregnancies. The levels of energy metabolism factors (C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide (GlP), glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, and visfatin) in blood plasma were determined using a multiplex assay (10-plex Bio-Plex Pro Human Diabetes Panel test system).

Results: Analysis of maternal plasma energy metabolism factors revealed significant increases in GLP-1 and PAI-1 levels in the FGR (p=0.003 and p=0.004, respectively). Women with FGR before 37 weeks of gestation showed significant differences in leptin (p=0.05) and PAI-1 (p=0.006) levels compared with those without FGR. After 37 weeks of pregnancy, significant differences were observed in GLP-1 and glucagon levels (p=0.005 and p=0.01, respectively). This study also found that the insulin/GLP-1 ratio was significantly lower in the FGR group than in the control group (p<0.001), suggesting the development of pancreatic cell resistance to GLP-1 and a compensatory increase in its plasma levels in women with FGR. Additionally, a statistically significant direct correlation (rs=0.35, p=0.05) was observed between GLP-1 and PAI-1 (a fibrinolysis inhibitor and a pathogenetically significant factor in FGR). The combination of five factors (GLP-1, glucagon, insulin, leptin, and PAI-1) exhibited excellent diagnostic performance, with an area under the ROC curve of 0.92, a sensitivity of 96%, and a specificity of 81%.

Conclusion: The study results suggest the potential involvement of energy metabolism factors in the development of FGR and highlight prospects for further exploration. Determining the blood plasma levels of GLP-1 and PAI-1 in women with FGR could serve as new non-invasive markers for diagnosing FGR during pregnancy. Furthermore, a combination of factors (GLP-1, glucagon, insulin, leptin, and PAI-1) could identify FGR with high diagnostic accuracy.

Sobre autores

Natalia Kan

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

Email: kan-med@mail.ru
ORCID ID: 0000-0001-5087-5946
Código SPIN: 5378-8437
Scopus Author ID: 57008835600
Researcher ID: B-2370-2015

Professor, Dr. Med. Sci., Deputy Director of Science

Rússia, Moscow

Ekaterina Soldatova

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

Autor responsável pela correspondência
Email: katerina.soldatova95@bk.ru
ORCID ID: 0000-0001-6463-3403

PhD student

Rússia, Moscow

Victor Tyutyunnik

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

Email: tioutiounnik@mail.ru
ORCID ID: 0000-0002-5830-5099
Código SPIN: 1963-1359
Scopus Author ID: 56190621500
Researcher ID: B-2364-2015

Professor, Dr. Med. Sci., Leading Researcher at the Center of Scientific and Clinical Research

Rússia, Moscow

Anastasia Borisova

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

Email: vvv92@list.ru

PhD student

Rússia, Moscow

Yurii Tezikov

Samara State Medical University, Ministry of Health of Russia

Email: yra.75@inbox.ru
ORCID ID: 0000-0002-8946-501X
Código SPIN: 2896-6986
Researcher ID: С-6187-2018

Professor, Dr. Med. Sci., Head of the Department of Obstetrics and Gynecology of the Institute of Clinical Medicine

Rússia, Samara

Igor Lipatov

Samara State Medical University, Ministry of Health of Russia

Email: i.lipatoff2012@yandex.ru
ORCID ID: 0000-0001-7277-7431
Código SPIN: 9625-2947
Scopus Author ID: 6603787595
Researcher ID: С-5060-2018

Professor, Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology of the Institute of Clinical Medicine

Rússia, Samara

Alsu Sadekova

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

Email: a_sadekova@oparina4.ru
ORCID ID: 0000-0003-4726-7477

PhD (Bio), Researcher at the Cytology Laboratory

Rússia, Moscow

Aleksey Alekseev

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

Email: a_alekseev@oparina4.ru
ORCID ID: 0000-0002-5347-6884

Junior Researcher at the Cytology Laboratory

Rússia, Moscow

Aleksey Krasnyi

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

Email: alexred@list.ru
ORCID ID: 0000-0001-7883-2702

PhD (Bio), Head of the Cytology Laboratory

Rússia, Moscow

Bibliografia

  1. Nardozza L.M., Caetano A.C., Zamarian A.C., Mazzola J.B., Silva C.P., Marçal V.M. et al. Fetal growth restriction: current knowledge. Arch. Gynecol. Obstet. 2017; 295(5): 1061-77. https://dx.doi.org/10.1007/s00404-017-4341-9.
  2. Министерство здравоохранения Российской Федерации. Клинические рекомендации. Недостаточный рост плода, требующий предоставления медицинской помощи матери (задержка роста плода). М.; 2022. 76с. [Ministry of Health of the Russian Federation. Clinical guidelines. Insufficient fetal growth requiring maternal medical care (fetal growth restriction). Moscow; 2022. 76p. (in Russian)].
  3. Hales C.N., Barker D.J. The thrifty phenotype hypothesis. Br. Med. Bull. 2001; 60: 5-20. https://dx.doi.org/10.1093/bmb/60.1.5.
  4. Oke S.L., Hardy D.B. The role of cellular stress in intrauterine growth restriction and postnatal dysmetabolism. Int. J. Mol. Sci. 2021; 22(13): 6986. https://dx.doi.org/10.3390/ijms22136986.
  5. Солдатова Е.Е., Кан Н.Е., Тютюнник В.Л., Волочаева М.В. Задержка роста плода с позиции фетального программирования. Акушерство и гинекология. 2022; 8: 5-10. [Soldatova E.E., Kan N.E., Tyutyunnik V.L., Volochaeva M.V. Fetal growth retardation from the perspective of fetal programming. Obstetrics and Gynecology. 2022; (8): 5-10. (in Russian)]. https://dx.doi.org/10.18565/aig.2022.8.5-10.
  6. Кан Н.Е., Солдатова Е.Е., Тютюнник В.Л., Волочаева М.В., Садекова А.А., Красный А.М. Диагностическая значимость определения экспрессии генов энергетического метаболизма при задержке роста плода. Акушерство и гинекология. 2023; 8: 48-55. [Kan N.E., Soldatova E.E., Tyutyunnik V.L., Volochaeva M.V., Sadekova A.A., Krasnyi A.M. Diagnostic significance of determining the expression of energy metabolism genes in fetal growth retardation. Obstetrics and Gynecology. 2023; (8): 48-55. (in Russian)]. https://dx.doi.org/10.18565/aig.2023.93.
  7. Рюмина И.И., Байбарина Е.Н., Нароган М.В., Маркелова М.М., Орловская И.В., Зубков В.В., Дегтярев Д.Н. Использование международных стандартов роста для оценки физического развития новорожденных и недоношенных детей. Неонатология: новости, мнения, обучение. 2023; 11(2): 48-52. [Ryumina I.I., Baibarina E.N., Narogan M.V., Markelova M.M., Orlovskaya I.V., Zubkov V.V., Degtyarev D.N. The usage of the international growth standards to assess the physical development of newborn and premature children. Neonatology: News, Opinions, Training. 2023; 11(2): 48-52. (in Russian)]. https://dx.doi.org/10.33029/2308-2402-2023-11-2-48-52.
  8. de Knegt V.E., Hedley P.L., Kanters J.K., Thagaard I.N., Krebs L., Christiansen M. et al. The role of leptin in fetal growth during pre-eclampsia. Int. J. Mol. Sci. 2021; 22(9): 4569. https://dx.doi.org/10.3390/ijms22094569.
  9. Masuzaki H., Ogawa Y., Sagawa N., Hosoda K., Matsumoto T., Mise H. et al. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat. Med. 1997; 3(9): 1029-33. https://dx.doi.org/10.1038/nm0997-1029.
  10. Schanton M., Maymó J.L., Pérez-Pérez A., Sánchez-Margalet V., Varone C.L. Involvement of leptin in the molecular physiology of the placenta. Reproduction. 2018; 155(1): R1-R12. https://dx.doi.org/10.1530/REP-17-0512.
  11. D'Ippolito S., Tersigni C., Scambia G., Di Simone N. Adipokines, an adipose tissue and placental product with biological functions during pregnancy. Biofactors. 2012; 38(1): 14-23. https://dx.doi.org/10.1002/biof.201.
  12. Pérez-Pérez A., Toro A., Vilariño-García T., Maymó J., Guadix P., Dueñas J.L. et al. Leptin action in normal and pathological pregnancies. J. Cell. Mol. Med. 2018; 22(2): 716-27. https://dx.doi.org/10.1111/jcmm.13369.
  13. Khant Aung Z., Grattan D.R., Ladyman S.R. Pregnancy-induced adaptation of central sensitivity to leptin and insulin. Mol. Cell. Endocrinol. 2020; 516: 110933. https://dx.doi.org/10.1016/j.mce.2020.110933.
  14. Yildiz L., Avci B., Ingeç M. Umbilical cord and maternal blood leptin concentrations in intrauterine growth retardation. Clin. Chem. Lab. Med. 2002; 40(11): 1114-7. https://dx.doi.org/10.1515/CCLM.2002.195.
  15. Mise H., Yura S., Itoh H., Nuamah M.A., Takemura M., Sagawa N. et al. The relationship between maternal plasma leptin levels and fetal growth restriction. Endocr. J. 2007; 54(6): 945-51. https://dx.doi.org/10.1507/endocrj.k06-225.
  16. Savvidou M.D., Sotiriadis A., Kaihura C., Nicolaides K.H., Sattar N. Circulating levels of adiponectin and leptin at 23-25 weeks of pregnancy in women with impaired placentation and in those with established fetal growth restriction. Clin. Sci. (Lond). 2008; 115(7): 219-24. https://dx.doi.org/10.1042/CS20070409.
  17. Müller T.D., Finan B., Bloom S.R., D'Alessio D., Drucker D.J., Flatt P.R. et al. Glucagon-like peptide 1 (GLP-1). Mol. Metab. 2019; 30: 72-130. https://dx.doi.org/10.1016/j.molmet.2019.09.010.
  18. Drucker D.J., Habener J.F., Holst J.J. Discovery, characterization, and clinical development of the glucagon-like peptides. J. Clin. Invest. 2017; 127(12): 4217-27. https://dx.doi.org/10.1172/JCI97233.
  19. Hefetz L., Ben-Haroush Schyr R., Bergel M., Arad Y., Kleiman D., Israeli H. et al. Maternal antagonism of Glp1 reverses the adverse outcomes of sleeve gastrectomy on mouse offspring. JCI Insight. 2022; 7(7): e156424. https://dx.doi.org/10.1172/jci.insight.156424.
  20. Mehdi S.F., Pusapati S., Anwar M.S., Lohana D., Kumar P., Nandula S.A. et al. Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent. Front. Immunol. 2023; 14: 1148209. https://dx.doi.org/10.3389/fimmu.2023.1148209.
  21. Ma Z., Paek D., Oh C.K. The cAMP/PKA pathway positively regulates PAI-1 expression in human mast cells. J. Allergy Clin. Immunol. 2009; 123(2): S214. https://dx.doi.org/10.1016/j.jaci.2008.12.818.
  22. Sheppard B.L., Bonnar J. Uteroplacental hemostasis in intrauterine fetal growth retardation. Semin. Thromb. Hemost. 1999; 25(5): 443-6. https://dx.doi.org/10.1055/s-2007-994947.
  23. Kaufmann P., Black S., Huppertz B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol. Reprod. 2003; 69(1): 1-7. https://dx.doi.org/10.1095/biolreprod.102.014977.
  24. Kam E.P., Gardner L., Loke Y.W., King A. The role of trophoblast in the physiological change in decidual spiral arteries. Hum. Reprod. 1999; 14(8): 2131-8. https://dx.doi.org/10.1093/humrep/14.8.2131.

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2. Fig. 1. Factors of energy metabolism in maternal plasma in groups before 37 weeks and after 37 weeks of gestation (*p<0.05, **p<0.005)

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3. Fig. 2. Relationship between insulin and GLP-1 in the presence and absence of PRA

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4. Fig. 3. ROS curve for the diagnosis of PPD based on the determination of energy metabolism factors (GLP-1, glucagon, insulin, leptin and PAI-1) in maternal blood plasma

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