Factors of energy metabolism in fetal growth restriction

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Abstract

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.

About the authors

Natalia E. 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
SPIN-code: 5378-8437
Scopus Author ID: 57008835600
ResearcherId: B-2370-2015

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

Russian Federation, Moscow

Ekaterina E. Soldatova

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

Author for correspondence.
Email: katerina.soldatova95@bk.ru
ORCID iD: 0000-0001-6463-3403

PhD student

Russian Federation, Moscow

Victor L. 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
SPIN-code: 1963-1359
Scopus Author ID: 56190621500
ResearcherId: B-2364-2015

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

Russian Federation, Moscow

Anastasia G. 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

Russian Federation, Moscow

Yurii V. Tezikov

Samara State Medical University, Ministry of Health of Russia

Email: yra.75@inbox.ru
ORCID iD: 0000-0002-8946-501X
SPIN-code: 2896-6986
ResearcherId: С-6187-2018

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

Russian Federation, Samara

Igor S. Lipatov

Samara State Medical University, Ministry of Health of Russia

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

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

Russian Federation, Samara

Alsu A. 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

Russian Federation, Moscow

Aleksey A. 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

Russian Federation, Moscow

Aleksey M. 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

Russian Federation, Moscow

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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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