diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13424diaendo-13424Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESМикроРНК как мишени и биомаркеры фиброза миокарда у больных сахарным диабетом 1 типаMicroRNAs as targets and biomarkers of myocardial fibrosis in patients with type 1 diabetes mellitushttps://orcid.org/0000-0003-3370-8630ВенгржиновскаяО. И.VengrzhinovskayaO. I.

Венгржиновская Оксана Игоревна - к.м.н.

117292, Москва, ул. Дм. Ульянова, д. 11

Oksana I. Vengrzhinovskaya - MD, PhD.

11 Dm. Ulyanova street, 117292 Moscow

vengrzhinovskay@gmail.comhttps://orcid.org/0000-0002-5178-6029БондаренкоИ. З.BondarenkoI. Z.

Бондаренко Ирина Зиятовна - д.м.н., профессор.

117292, Москва, ул. Дм. Ульянова, д. 11

Irina Z. Bondarenko - MD, PhD, Professor.

11 Dm. Ulyanova street, 117292 Moscow

bondarenko.irina@endocrincentr.ruhttps://orcid.org/0000-0003-1831-8052ШацкаяО. А.ShatskayaO. A.

Шацкая Ольга Александровна - к.м.н., в.н.с.

117292, Москва, ул. Дм. Ульянова, д. 11

Olga A. Shatskaya - MD, PhD, leading researcher.

11 Dm. Ulyanova street, 117292 Moscow

shackaya.olga@endocrincentr.ruhttps://orcid.org/0009-0007-0939-7824ЛобковаА. A.LobkovaA. A.

Лобкова Алина Александровна.

117292, Москва, ул. Дм. Ульянова, д. 11

Alina A. Lobkova.

11 Dm. Ulyanova street, 117292 Moscow

alinalobkova1408@gmail.comhttps://orcid.org/0000-0001-7965-9454ТарбаеваН. В.TarbaevaN. V.

Тарбаева Наталья Викторовна - к.м.н.

117292, Москва, ул. Дм. Ульянова, д. 11

Natalya V. Tarbaeva - MD, PhD.

11 Dm. Ulyanova street, 117292 Moscow

tarbaeva.natalya@endocrincentr.ruhttps://orcid.org/0009-0007-4475-8752КорнелюкА. Ю.KornelyukA. Y.

Корнелюк Анастасия Юрьевна.

117292, Москва, ул. Дм. Ульянова, д. 11

Anastasiya Y. Kornelyuk.

11 Dm. Ulyanova street, 117292 Moscow

korneluk.anastasya@endocrincentr.ruhttps://orcid.org/0000-0001-5573-0754КалашниковВ. Ю.KalashnikovV. Y.

Калашников Виктор Юрьевич - д.м.н., профессор, чл.-корр. РАН.

117292, Москва, ул. Дм. Ульянова, д. 11

Viktor Y. Kalashnikov - MD, PhD, Professor.

11 Dm. Ulyanova street, 117292 Moscow

kalashnikov.victor@endocrincentr.ruhttps://orcid.org/0000-0002-5057-127XШестаковаМ. В.ShestakovaM. V.

Шестакова Марина Владимировна - д.м.н., профессор, академик РАН.

117292, Москва, ул. Дм. Ульянова, д. 11

Marina V. Shestakova - MD, PhD, Professor, Academician of the RAS.

11 Dm. Ulyanova street, 117292 Moscow

shestakova.marina@endocrincentr.ruhttps://orcid.org/0000-0002-9717-9742МокрышеваН. Г.MokryshevaN. G.

Мокрышева Наталья Георгиевна - д.м.н., профессор, академик РАН.

117292, Москва, ул. Дм. Ульянова, д. 11

Researcher ID AAY-3761-2020; Scopus Author ID 35269746000

Natalya G. Mokrysheva - MD, PhD, Professor, Academician of the RAS.

11 Dm. Ulyanova street, 117292 Moscow

Researcher ID AAY-3761-2020; Scopus Author ID 35269746000

mokrisheva.natalia@endocrincentr.ruГНЦ РФ ФГБУ «Национальный медицинский исследовательский центр эндокринологии имени академика И.И. Дедова»РоссияEndocrinology Research CentreRussian Federation202517012026286523532Copyright © Венгржиновская О.И., Бондаренко И.З., Шацкая О.А., Лобкова А.A., Тарбаева Н.В., Корнелюк А.Ю., Калашников В.Ю., Шестакова М.В., Мокрышева Н.Г., 20262026Венгржиновская О.И., Бондаренко И.З., Шацкая О.А., Лобкова А.A., Тарбаева Н.В., Корнелюк А.Ю., Калашников В.Ю., Шестакова М.В., Мокрышева Н.Г.Vengrzhinovskaya O.I., Bondarenko I.Z., Shatskaya O.A., Lobkova A.A., Tarbaeva N.V., Kornelyuk A.Y., Kalashnikov V.Y., Shestakova M.V., Mokrysheva N.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/13424ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Структурно-морфологические изменения сердца у молодых пациентов с сахарным диабетом 1 типа (СД1) возникают на доклинической стадии кардиоваскулярных заболеваний и ухудшают сердечно-сосудистый прогноз у данной категории больных. Фиброз миокарда является одним из основных факторов, влияющих на ригидность миокарда желудочков и развитие сердечной недостаточности. Поиск ранних маркеров ремоделирования миокарда, среди которых особый интерес представляют микроРНК, позволит улучшить диагностику и снизить риск сердечно-сосудистых осложнений.

ЦЕЛЬ

ЦЕЛЬ. Изучить уровень экспрессии отдельных микроРНК, участвующих в процессах ремоделирования миокарда у молодых пациентов с СД1.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. Исследование проведено на базе ГНЦ РФ ФГБУ «НМИЦ эндокринологии имени академика И.И. Дедова» Минздрава России. В исследование включено 110 участников без сердечно-сосудистых заболеваний с разделением на 2 группы: 80 пациентов с СД1 (основная группа) и 30 человек без СД1 (группа сравнения). Всем участникам было проведено общеклиническое обследование, биоимпедансометрия, электрокардиография, магнитно-резонансной томографии (МРТ) сердца с применением технологии T-1 mapping (используется для количественного измерения фиброзных изменений миокарда, экстрацеллюлярной фракции и построением пиксельной схемы строения сердца), эргоспирометрия, оценка уровня экспрессии циркулирующих miR-126-5p и miR-21-5p.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. В группе пациентов с СД1, по данным обследования, выявлены признаки ремоделирования миокарда: по данным МРТ сердца — утолщение межжелудочковой перегородки (р=0,028), задней стенки левого желудочка (ЛЖ) (р=0,012), увеличение относительной толщины стенок ЛЖ (р<0,001) в сравнении с лицами без СД.

Также в группе пациентов с СД1 выявлены достоверно более низкие уровни кардиопротекторного miR-126-5p (р=0,046). Обращает на себя внимание наличие 8,7% пациентов с наличием фиброзной ткани в миокарде в группе пациентов с СД1. В группе контроля таких пациентов не было.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. МРТ сердца с отсроченным контрастированием является существенно более чувствительным по сравнению с эхокардиографией (Эхо-КГ) в отношении выявления диффузного фиброза миокарда, определяющего неблагоприятный сердечно-сосудистый прогноз. В проведенной работе в 8,7% случаев диффузный фиброз миокарда был выявлен у пациентов с СД1 с помощью МРТ сердца. Группа больных СД1 с диффузным фиброзом миокарда характеризовалась более выраженными начальными структурными изменения миокарда (по данным Эхо-КГ). У пациентов с СД1 наблюдаются более низкие уровни кардиопротективного микроРНК — miR-126-5p.

BACKGROUND

BACKGROUND: structural and morphological changes in the heart in young patients with type 1 diabetes mellitus occur at the preclinical stage of cardiovascular disease and worsen the cardiovascular prognosis in this group of patients. Myocardial fibrosis is one of the main factors influencing ventricular myocardial stiffness and the development of heart failure. The search for early markers of myocardial remodeling, among which microRNAs are of particular interest, will improve diagnosis and reduce the risk of cardiovascular complications.

OBJECTIVE

OBJECTIVE: to study the expression levels of individual microRNAs involved in myocardial remodeling processes in young patients with type 1 diabetes mellitus.

MATERIALS AND METHODS

MATERIALS AND METHODS: the study was conducted at the Federal State Budgetary Institution “I.I. Dedov National Medical Research Center of Endocrinology” of the Ministry of Health of the Russian Federation. The study included 110 participants without cardiovascular disease, divided into 2 groups: 80 patients with type 1 diabetes (the study group) and 30 ­individuals without type 1 diabetes (control group). All participants underwent a general clinical examination, bioimpedance analysis, electrocardiography, cardiac MRI with T-1 mapping technology (used for quantitative assessment of myocardial fibrotic changes, extracellular volume fraction, and construction of pixel-wise heart structure maps), ergospirometry, and assessment of circulating miR-126-5p and miR-21-5p expression levels.

RESULTS

RESULTS: in the group of patients with type 1 diabetes, examination revealed signs of myocardial remodeling: сardiac MRI revealed thickening of the interventricular septum (p=0.028), left ventricular posterior wall (p=0.012), and left ventricular relative wall thickness (p<0.001), compared with individuals without type 1 diabetes. Additionally, patients with type 1 diabetes demonstrated significantly lower levels of cardioprotective miR-126-5p (p=0.046). It is noteworthy that 8.7% of patients in the type 1 diabetes group had fibrous tissue in the myocardium. No such patients were detected in the control group.

CONCLUSION

CONCLUSION: cardiac MRI with late gadolinium enhancement is significantly more sensitive than echocardiography in detecting diffuse myocardial fibrosis, which indicates an unfavorable cardiovascular prognosis. In this study, diffuse myocardial fibrosis was detected by cardiac MRI in 8.7% of patients with type 1 diabetes. The group of type 1 diabetes patients with diffuse myocardial fibrosis was characterized by more pronounced initial structural myocardial changes (according to echocardiographic data). Patients with type 1 diabetes demonstrate lower levels of cardioprotective microRNA — miR-126-5p.

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The authors declare that there are no conflicts of interest present.