Hormone metabolic pattern in the preclinical stage of preeclampsia

Abstract

BACKGROUND: The imbalance of vascular endothelial cell metabolism determines the clinical manifestations of preeclampsia; however, the molecular mechanisms underlying the vessel destabilization are not fully understood. In recent years, researchers have focused on clarifying the role of dysmetabolic disorders in patients with obstetric pathology, including preeclampsia. This is due to the fact that pregnancy is accompanied by metabolic restructuring aimed at switching the energy supply of the pregnant woman’s body from the carbohydrate to the fat component in order to maintain an effective energoplastic supply of the developing fetus. Impairment of this evolutionary adaptation mechanism realized during pregnancy requires additional in-depth study.

AIM: This study was aimed to identify and compare pathogenetic patterns that characterize early and late preeclampsia at the preclinical stage, based on dynamic clinical and laboratory examination of high-risk pregnant women.

MATERIALS AND METHODS: A prospective clinical and laboratory examination of 180 pregnant women with independent factors of high risk of developing preeclampsia was carried out. Comparison groups were identified retrospectively, depending on the period of preeclampsia manifestation: Group I consisted of 31 pregnant women with early preeclampsia; Group II comprised 58 pregnant women with late preeclampsia; and Group III (control) included 30 healthy pregnant women with uncomplicated gestation. Pregnant women were examined twice at the preclinical stage of preeclampsia (11-14 and 18-21 weeks of gestation) and once at clinical manifestation of the disease (28-36 weeks of gestation). The markers of metabolic, hormonal, hemocirculatory, hemostasiological and placental disorders were evaluated.

RESULTS: We found similar pathophysiological changes in pregnant women with both early and late PE, from early gestation periods. Those were characterized by pathological insulin resistance and hyperinsulinemia, as well as associated atherogenic changes in the lipid profile, hyperleptinemia, hyperuricemia, hypersympathicotonia, visceral fat deposition, and contra-insular hormonal deviations. The observed alterations reflected a single hormonal and metabolic pattern of the preclinical stage of preeclampsia. During pregnancy, there was shown an increase in clustering diabetogenic and atherogenic abnormalities and hormonal changes, which were supplemented by associated endothelial and hemostasiological dysfunction and, in early preeclampsia, placental dysfunction, thus accelerating the time of clinical implementation of preeclampsia.

CONCLUSIONS: From the pathogenetic point of view, preeclampsia of various periods of manifestation is an indivisible category with a common basic developmental mechanism characterized by a hormone metabolic pattern from the early stages of pregnancy. These stable changes are the result of the pathologically transformed phylogenetic mechanism of energoplastic supply of the fetus. This transformation is realized via physiological insulin resistance and compensatory hyperinsulinemia development due to the contra-insular activity of placental hormones. The added structural and functional disorders of the embryo (feto) placental system potentiate basic mechanisms (pathological insulin resistance and hyperinsulinemia) and determine the period of preeclampsia clinical manifestation in each particular woman.

Keywords

early preeclampsia / late preeclampsia / pathogenesis / contrainsular placental hormones / insulin resistance / hyperinsulinemia / dyslipidemia / endothelial hemostasiological disorders / placental dysfunction

References

[1] Bezhenar VF, Adamyan LV, Filippov OS, et al. Maternal mortality in the Northwestern Federal Region of the Russian Federation: a comparative analysis 2018–2019, conceptual approaches to reduction. Russian Journal of Human Reproduction. 2020;26(6–2):33–41. (In Russ.). DOI: 10.17116/repro20202606233

[2] Беженарь В.Ф., Адамян Л.В., Филиппов О.С. и др. Материнская смертность в Северо-Западном федеральном округе Российской Федерации: сравнительный анализ 2018–2019 гг., концептуальные подходы к снижению // Проблемы репродукции. 2020. Т. 26. № 6–2. С. 33–41. DOI: 10.17116/repro20202606233

[3] Stevens AB, Brasuell DM, Higdon RN. Atypical preeclampsia — gestational proteinuria. J Family Med Prim Care. 2017;6(3):669–671. DOI: 10.4103/2249-4863.222029

[4] Stevens A.B., Brasuell D.M., Higdon R.N. Atypical preeclampsia — gestational proteinuria // J. Family Med. Prim. Care. 2017. Vol. 6. No. 3. P. 669–671. DOI: 10.4103/2249-4863.222029

[5] Echeverria C, Eltit F, Santibanez JF, et al. Endothelial dysfunction in pregnancy metabolic disorders. Biochim Biophys Acta Mol Basis Dis. 2020;1866(2):165414. DOI: 10.1016/j.bbadis.2019.02.009

[6] Echeverria C., Eltit F., Santibanez J.F. et al. Endothelial dysfunction in pregnancy metabolic disorders // Biochim. Biophys. Acta Mol. Basis. Dis. 2020. Vol. 1866. No. 2. P. 165414. DOI: 10.1016/j.bbadis.2019.02.009

[7] Strizhakov AN, Timokhina EV, Ibragimova SM, et al. New possibilities for differential prediction of early onset and late onset preeclampsia. Obstetrics, Gynecology and Reproduction. 2018;12(2):55–61. (In Russ.). DOI: 10.17749/2313-7347.2018.12.2.055-061

[8] Стрижаков А.Н., Тимохина Е.В., Ибрагимова С.М. и др. Новые возможности дифференциального прогнозирования ранней и поздней преэклампсии // Акушерство, гинекология и репродукция. 2018. Т. 12. № 2. С. 55–61. DOI: 10.17749/2313-7347.2018.12.2.055-061

[9] Makatsariya AD, Serov VN, Gris JCh, et al. Catastrophic antiphospholipid syndrome and thromboses. Obstetrics and Gynecology. 2019;(9):5–14. (In Russ.). DOI: 10.18565/aig.2019.9.5-14

[10] Макацария А.Д., Серов В.Н., Гри Ж.К. и др. Катастрофический антифосфолипидный синдром и тромбозы // Акушерство и гинекология. 2019. № 9. С. 5–14. DOI: 10.18565/aig.2019.9.5-14

[11] Aulamazyan EK, Evsyukova II, Yarmolinskaya MI. The role of melatonin in development of gestational diabetes mellitus. Journal of Obstetrics and Women’s Diseases. 2017;67(1):85–91. (In Russ.). DOI: 10.17816/JOWD67185-91

[12] Айламазян Э.К., Евсюкова И.И., Ярмолинская М.И. Роль мелатонина в развитии гестационного сахарного диабета // Журнал акушерства и женских болезней. 2018. Т. 67. № 1. С. 85–91. DOI: 10.17816/JOWD67185-91

[13] Nolan CJ, Prentki M. Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: Time for a conceptual framework shift. Diab Vasc Dis Res. 2019;16(2):118–127. DOI: 10.1177/1479164119827611

[14] Nolan C.J., Prentki M. Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: Time for a conceptual framework shift // Diab. Vasc. Dis. Res. 2019;16(2):118–127. DOI: 10.1177/1479164119827611

[15] Savel’eva GM, Shalina RI, Konoplyannikov AG, Simuhina MA. Pre-eclampsia and eclampsia: new approaches in diagnosis and evaluation of severity. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie. 2018;6(4):25–30. (In Russ.). DOI: 10.24411/2303-9698-2018-14002

[16] Савельева Г.М., Шалина Р.И., Коноплянников А.Г., Симухина М.А. Преэклампсия и эклампсия: новые подходы к диагностике и оценке степени тяжести. Акушерство и гинекология: новости, мнения, обучение. 2018. Т. 6. № 4. С. 25–30. DOI: 10.24411/2303-9698-2018-14002

[17] Redman CW. Early and late onset preeclampsia: Two sides of the same coin. Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health. 2017;7:58. DOI: 10.1016/j.preghy.2016.10.011

[18] Redman CW. Early and late onset preeclampsia: Two sides of the same coin // Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health. 2017. Vol. 7. P. 58. DOI: 10.1016/j.preghy.2016.10.011

[19] Tezikov YuV, Lipatov IS. Results of carbogenotherapy for the prevention of placental insufficiency. Rossiiskii vestnik akushera-ginekologa. 2011;11(5):71–77. (In Russ.)

[20] Тезиков Ю.В., Липатов И.С. Результаты применения карбогенотерапии для профилактики плацентарной недостаточности // Российский вестник акушера-гинеколога. 2011. Т. 11. № 5. С. 71–77.

[21] Chen X, Stein TP, Steer RA, Scholl TO. Individual free fatty acids have unique associations with inflammatory biomarkers, insulin resistance and insulin secretion in healthy and gestational diabetic pregnant women. BMJ Open Diabetes Res Care. 2019;7(1):e000632. DOI: 10.1136/bmjdrc-2018-000632

[22] Chen X., Stein T.P., Steer R.A., Scholl T.O. Individual free fatty acids have unique associations with inflammatory biomarkers, insulin resistance and insulin secretion in healthy and gestational diabetic pregnant women // BMJ Open Diabetes Res. Care. 2019. Vol. 7. No. 1. P. e000632. DOI: 10.1136/bmjdrc-2018-000632

[23] Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019;15(5):275–289. DOI: 10.1038/s41581-019-0119-6

[24] Phipps E.A., Thadhani R., Benzing T., Karumanchi S.A. Pre-eclampsia: pathogenesis, novel diagnostics and therapies // Nat. Rev. Nephrol. 2019. Vol. 15. No. 5. P. 275–289. DOI: 10.1038/s41581-019-0119-6

[25] Tayama K, Inukai T, Shimomura Y. Preperitoneal fat deposition estimated by ultrasonography in patients with non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1999;43(1):49–58. DOI: 10.1016/s0168-8227(98)00118-1

[26] Tayama K., Inukai T., Shimomura Y. Preperitoneal fat deposition estimated by ultrasonography in patients with non-insulin-dependent diabetes mellitus // Diabetes Res. Clin. Pract. 1999. Vol. 43. No. 1. P. 49–58. DOI: 10.1016/s0168-8227(98)00118-1

[27] Gipertenzivnye rasstrojstva vo vremja beremennosti, v rodah i poslerodovom periode. Prejeklampsija. Jeklampsija. Klinicheskie rekomendacii (Protokol lechenija). 2016. (In Russ.). [cited 22 Jan 2021]. Available from: http://www.rokb.ru/sites/default/files/pictures/gipertenzivnye_rasstroystva_vo_vremya_beremennosti_v_rodah_i_poslerodovom_periode._preeklampsiya._eklampsiya.pdf

[28] Гипертензивные расстройства во время беременности, в родах и послеродовом периоде. Преэклампсия. Эклампсия. Клинические рекомендации (Протокол лечения). 2016. [дата обращения 22.01.2021]. Доступ по ссылке: http://www.rokb.ru/sites/default/files/pictures/gipertenzivnye_rasstroystva_vo_vremya_beremennosti_v_rodah_i_poslerodovom_periode._preeklampsiya._eklampsiya.pdf

[29] Strizhakov AN, Tezikov YuV, Lipatov IS, et al. Standardization of diagnostics and clinical classification of chronic placental insufficiency. Gynecology, Obstetrics and Perinatology. 2014;13(3):5–12. (In Russ.)

[30] Стрижаков А.Н., Тезиков Ю.В., Липатов И.С. и др. Стандартизация диагностики и клиническая классификация хронической плацентарной недостаточности // Вопросы гинекологии, акушерства и перинатологии. 2014. Т. 13. № 3. С. 5–12.

[31] Napso T, Yong HEJ, Lopez-Tello J, Sferruzzi-Perri AN. The role of placental hormones in mediating maternal adaptations to support pregnancy and lactation. Front Physiol. 2018;9:1091. DOI: 10.3389/fphys.2018.01091

[32] Napso T., Yong H.E.J., Lopez-Tello J., Sferruzzi-Perri A.N. The role of placental hormones in mediating maternal adaptations to support pregnancy and lactation // Front. Physiol. 2018. Vol. 9. P. 1091. DOI: 10.3389/fphys.2018.01091

[33] Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis. 2017;11(8):215–225. DOI: 10.1177/1753944717711379

[34] Rochlani Y., Pothineni N.V., Kovelamudi S., Mehta J.L. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds // Ther. Adv. Cardiovasc. Dis. 2017. Vol. 11. No. 8. P. 215–225. DOI: 10.1177/1753944717711379

[35] Algoritmy vedenija pacienta s arterial’noj gipertenziej gipertonicheskim krizom. Obshherossijskaja obshhestvennaja organizacija “Sodejstvija profilaktike i lecheniju arterial’noj gipertenzii “Antigipertenzivnaja Liga”. Saint Petersburg; 2019. (In Russ.). [cited 2021 Apr 25]. Available from: https://scardio.ru/content/documents/algorythmy.pdf

[36] Алгоритмы ведения пациента с артериальной гипертензией и гипертоническим кризом. Общероссийская общественная организация «Содействия профилактике и лечению артериальной гипертензии «Антигипертензивная лига». Санкт-Петербург, 2019. [дата обращения 25.04.2021]. Доступ по ссылке: https://scardio.ru/content/documents/algorythmy.pdf

[37] Ökdemir D, Hatipoğlu N, Kurtoğlu S, et al. The role of rrisin, rnsulin and leptin in maternal and fetal interaction. J Clin Res Pediatr Endocrinol. 2018;10(4):307–315. DOI: 10.4274/jcrpe.0096

[38] Ökdemir D., Hatipoğlu N., Kurtoğlu S. et al. The role of irisin, insulin and leptin in maternal and fetal interaction // J. Clin. Res. Pediatr. Endocrinol. 2018. Vol. 10. No. 4. P. 307–315. DOI: 10.4274/jcrpe.0096

[39] Katkova NY, Bodrikova OI, Sergeeva AV, Andosova LD, Shahova KA, Bezrukova IM, et al. The state of the local immune status, the content of neopterin and cortisol in different variants of preterm labor. Journal of Obstetrics and Women’s Diseases. 2017;66(3):60–70. (In Russ.). DOI: 10.17816/JOWD66360-70

[40] Каткова Н.Ю., Бодрикова О.И., Сергеева А.В. и др. Состояние локального иммунного статуса, содержание неоптерина и кортизола при различных вариантах преждевременных родов // Журнал акушерства и женских болезней. 2017. Т. 66. № 3. C. 60–70. DOI: 10.17816/JOWD66360-70

[41] Romantsova TI, Sych YP. Immunometabolism and metainflammation in obesity. Obesity and metabolism. 2019;16(4):3–17. (In Russ.). DOI: 10.14341/omet12218

[42] Романцова Т.И., Сыч Ю.П. Иммунометаболизм и метавоспаление при ожирении // Ожирение и метаболизм. 2019. Т. 16. № 4. С. 3–17. DOI: 10.14341/omet12218

[43] Belinina AA, Mozgovaya EV, Remneva OV. Spectrum of genetic thrombophilia in pregnant women with varying severity of preeclampsia. Bulletin of Medical Science. 2020;1(17):28–32. (In Russ.)

[44] Белинина А.А., Мозговая Е.В., Ремнёва О.В. Спектр генетических тромбофилий у беременных с различной степенью тяжести преэклампсии // Бюллетень медицинской науки. 2020. № 1 (17). С. 29–33.

[45] Bezbabicheva TS. Contradictory properties of uric acid and aspects of the biochemistry of arterial hypertension. Natural resources of the Earth and environmental protection. 2020;l(10–11–12):78–80. (In Russ.). DOI: 10.26787/nydha-2713-203X-2020-1-10-11-12-78-80

[46] Безбабичева Т.С. Противоречивые свойства мочевой кислоты и аспекты биохимии артериальной гипертензии // Natural resources of the Earth and environmental protection. 2020. T. 1. № 10–11–12. C. 78–80. DOI: 10.26787/nydha-2713-203X-2020-1-10-11-12-78-80

[47] Lipatov IS, Tezikov YuV, Santalova GV, Ovchinnikova MA. Prevention of recurrent herpetic infection in pregnant women and intrauterine infection of the fetus with the herpes simplex virus. Rossiiskii vestnik akushera-ginekologa. 2014;14(4):63–68. (In Russ.)

[48] Липатов И.С., Тезиков Ю.В., Санталова Г.В., Овчинникова М.А. Профилактика рецидивов герпетической инфекции у беременных и внутриутробного инфицирования плода вирусом простого герпеса // Российский вестник акушера-гинеколога. 2014. Т. 14. № 4. С. 63–68.

[49] Ngala RA, Fondjo LA, Gmagna P, et al. Placental peptides metabolism and maternal factors as predictors of risk of gestational diabetes in pregnant women. A case-control study. PLoS One. 2017;12(7):e0181613. DOI: 10.1371/journal.pone.0181613

[50] Ngala R.A., Fondjo L.A., Gmagna P. et al. Placental peptides metabolism and maternal factors as predictors of risk of gestational diabetes in pregnant women. A case-control study // PLoS One. 2017. Vol. 12. No. 7. P. e0181613. DOI: 10.1371/journal.pone.0181613

[51] Yuyun MF, Ng LL, Ng GA. Endothelial dysfunction, endothelial nitric oxide bioavailability, tetrahydrobiopterin, and 5-methyltetrahydrofolate in cardiovascular disease. Where are we with therapy? Microvasc Res. 2018;119:7–12. DOI: 10.1016/j.mvr.2018.03.012

[52] Yuyun M.F., Ng L.L., Ng G.A. Endothelial dysfunction, endothelial nitric oxide bioavailability, tetrahydrobiopterin, and 5-methyltetrahydrofolate in cardiovascular disease. Where are we with therapy? // Microvasc. Res. 2018. Vol. 119. P. 7–12. DOI: 10.1016/j.mvr.2018.03.012

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