Витамин D в предикции преэклампсии у женщин с гестационным сахарным диабетом

В связи с имеющимися публикациями о значении дефицита витамина D в формировании ГСД и сочетанных с ним осложнений представляется перспективным изучить метаболизм витамина D и определить его роль в патогенезе ПЭ у женщин с ГСД. Цель исследования - повысить эффективность прогнозирования и ранней диагностики ПЭ у пациенток с ГСД. Материал и методы. В данном двунаправленном когортном исследовании приняли участие 150 пациенток с ГСД, распределенных в две группы: 1-я - 75 беременных, у которых впоследствии развилась ПЭ (ГСД+ПЭ) и 2-я - только с ГСД (контрольная). Исследование проведено на клинической базе кафедры акушерства и гинекологии с курсом перинатологии Медицинского института ФГАОУ ВО РУДН им. Патриса Лумумбы, ГБУЗ ГКБ № 29 им. Н.Э. Баумана ДЗМ в период с 2023 по 2024 г. Диагностика ГСД и коморбидной с ГСД ПЭ проводилась согласно клиническим рекомендациям РФ. Метаболом (совокупность метаболитов) витамина D изучали в сроке 22-26 нед беременности методом высокоэффективной жидкостной хроматографии и масс-спектрометрии. Микроэлементный и биохимический анализ сыворотки крови выполнены фотометрическим и турбидиметрическим методами. Уровень паратгормона исследован хемилюминесцентным методом. Указанные выше анализы проводили в лаборатории метаболомных и протеомных исследований ГНЦ РФ ФГБУ «НМИЦ эндокринологии» Минздрава России. Для анализа полученных результатов использовалось программное обеспечение Microsoft Excel и IBM SPSS Statistics (версия 26) для MS Windows. Результаты. Изучаемые группы не различались по возрасту и прегестационному индексу массы тела (ИМТ). В группе ГСД+ПЭ гестационная прибавка массы тела (ГПМТ) был достоверно больше, чем в группе ГСД (6,24+6,1 против 2,2±2,3; p=0,006). Достоверных различий не наблюдалось в уровнях общего кальция, паратиреоидного гормона и фосфора плазмы крови. Уровни 25-OH-D₃ (25,34+15,36 против 24,91+7,6 нг/ мл; p=0,009) и общего 25-OH-D (25,85+15,34 против 25,42+7,61 нг/мл; p=0,009), а также 24,25-(OH)₂-D₃ (1,36+0,95 против 0,32+0,16 нг/мл; p<0,0001) оказались достоверно выше в группе ГСД+ПЭ, чем в группе ГСД. Прием витамина D в ходе прегравидарной подготовки (ПП), оцениваемый при сборе анамнеза независимо от при-

In the last decade, increase in the incidence of gestational diabetes mellitus (GDM) has outpaced all expectations and medical predictions. Along with this, there is a prevalence of complications associated with GDM, primarily preeclampsia (PE), which still occupies a leading place in the structure of maternal mortality. Despite the achievements of science and the search for various predictors of PE, the problem of predicting PE is far from being solved and remains relevant. Modern biomarkers allow predicting PE at the molecular level, but their effectiveness is not yet sufficient in clinical practice. In connection with the available publications on the importance of vitamin D deficiency in the development of GDM and associated complications, it seems promising to study the metabolism of vitamin D and determine its role in the pathogenesis of PE in women with GDM. The aim of the study was to improve the prognosis and early diagnosis of PE in patients with GDM. Material and methods. This bidirectional cohort study involved 150 patients with GDM, divided into two groups: 1^st - 75 pregnant women who subsequently developed PE (GDM+PE) and 2^nd - only with GDM (control). The study was conducted at the clinical base of the Department of Obstetrics and Gynecology with a course in perinatology of the Medical Institute of the Рeoples' Friendship University of Russia named after Patrice Lumumba, Clinical Hospital # 29 named after N.E. Bauman in the period from 2023 to 2024. Diagnostics of GDM and comorbid PE with GDM was carried out according to the clinical guidelines of the Russian Federation. The metabolome (set of metabolites) of vitamin D was studied at 22-26 weeks of pregnancy using high-performance liquid chromatography and mass spectrometry. Microelement and biochemical analysis of blood serum was performed using photometric and turbidimetric methods. The level of parathyroid hormone was studied using the chemiluminescent method. The above-mentioned analyses were carried out in the laboratory of metabolomic and proteomic studies of the Endocrinology Research Center, Ministry of Health of the Russian Federation. Microsoft Excel and IBM SPSS Statistics (version 26) for MS Windows software were used to analyze the obtained results. Results. The study groups did not differ in age and pregestational body mass index (BMI). In the GDM+PE group, gestational body weight gain (GBG) was significantly greater than in the GDM group (6.24+6.1 vs 2.2+2.3; p=0.006). No significant differences were observed in the levels of total calcium, parathyroid hormone, and plasma phosphorus. The levels of 25-OH-D₃ (25.34+15.36 vs 24.91+7.6 ng/ml; p=0.009) and total 25-OH-D (25.85+15.34 vs 25.42+7.61 ng/ml; p=0.009), as well as 24,25-(OH)₂-D₃ (1.36+0.95 vs 0.32+0.16 ng/ml; p<0.0001) were significantly higher in the GDM+PE group than in the GDM group. Vitamin D intake during preconception preparation (PP), assessed during anamnesis collection regardless of the dosage taken, did not correlate with the levels of 25-OH-D₃ and 24,25-(OH)₂-D₃ in the blood serum of patients in both groups. In turn, in both groups, a reliable positive correlation was observed between vitamin D intake and serum 1,25-(OH)₂-D₃ levels. When analyzing the vitamin D metabolome among patients who did not take its preparations as part of PP, a reliable difference remained only in the level of 24,25-(OH)₂-D₃ (1.04+0.99 in the GDM+PE group versus 0.22+0.1 ng/ml in the GDM group; p=0.036). Conclusion. When excluding the influence of age and initial BMI on metabolome parameters, the results of this study showed that women with GDM and associated PE had a more pronounced calcium-dependent hydroxylation of 25-OH-D₃ towards 24,25-(OH)₂-D₃ in the kidneys. Thus, 24,25-(OH)₂-D₃ can be considered as a potential marker of kidney damage before the clinical manifestation of PE. Once again, the direct effect of vitamin D intake on the level of the most active metabolite, 1,25-(OH)₂-D₃, has been proven, which plays a direct role in the prevention of GDM and associated complications, which should be taken into account in the framework of PP.