diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13059diaendo-13059Research ArticleОригинальные исследованияOriginal StudiesБиомаркеры сыворотки крови, ассоциированные с фиброзом печени, у больных сахарным диабетом 2 типаSerum biomarkers associated with liver fibrosis in patients with type 2 diabeteshttps://orcid.org/0000-0003-0091-2299КраснерЯ. А.KrasnerY. A.

Краснер Яков Аркадьевич - к.м.н., н.с.

Новосибирск

Yakov A. Krasner - MD, PhD, research associate.

Novosibirsk

yakov.krasner@yandex.ruРомановВ. В.RomanovV. V.

Романов Вячеслав Витальевич - н.с.; Scopus Author ID: 56810492000.

Новосибирск

Vyacheslav V. Romanov - MD, research associate; Scopus Author ID: 56810492000.

Novosibirsk

slavrom@mail.ruhttps://orcid.org/0000-0002-5868-579XФазуллинаО. Н.FazullinaO. N.

Фазуллина Ольга Николаевна - к.м.н., с.н.с.; Researcher ID: R-9382-2017; Scopus Author ID: 55554348400.

Новосибирск

Olga N. Fazullina - MD, PhD, senior research associate; Researcher ID: R-9382-2017; Scopus Author ID: 55554348400.

Novosibirsk

fazullina.olga@mail.ruhttps://orcid.org/0000-0002-5156-2842ОсипенкоМ. Ф.OsipenkoM. F.

Осипенко Марина Федоровна - д.м.н., профессор; Scopus Author ID: 6701825144.

Новосибирск

Marina F. Osipenko, MD, PhD, Professor; Scopus Author ID: 6701825144.

Novosibirsk

ngma@bk.ruhttps://orcid.org/0000-0002-5407-8722КлимонтовВ. В.KlimontovV. V.

Климонтов Вадим Валерьевич - д.м.н., профессор; Researcher ID: R-7689-2017; Scopus Author ID: 8295977000.

630060, Новосибирск, ул. Тимакова, 2

Vadim V. Klimontov - MD, PhD, Professor; Researcher ID: R-7689-2017; Scopus Author ID: 8295977000.

2 Timakov street, 630060 Novosibirsk

klimontov@mail.ruНаучно-исследовательский институт клинической и экспериментальной лимфологии — филиал ФГБНУ Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; ФГБОУ ВО Новосибирский государственный медицинский университет Минздрава РоссииРоссияResearch Institute of Clinical and Experimental Lymphology — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL — Branch of IC&G SB RAS); Novosibirsk State Medical UniversityRussian FederationНаучно-исследовательский институт клинической и экспериментальной лимфологии — филиал ФГБНУ Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияResearch Institute of Clinical and Experimental Lymphology — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL — Branch of IC&G SB RAS)Russian FederationФГБОУ ВО Новосибирский государственный медицинский университет Минздрава РоссииРоссияNovosibirsk State Medical UniversityRussian Federation2024180320242712532Copyright © Краснер Я.А., Романов В.В., Фазуллина О.Н., Осипенко М.Ф., Климонтов В.В., 20242024Краснер Я.А., Романов В.В., Фазуллина О.Н., Осипенко М.Ф., Климонтов В.В.Krasner Y.A., Romanov V.V., Fazullina O.N., Osipenko M.F., Klimontov V.V.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/13059ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Диагностика фиброза печени является важной задачей в ведении пациентов с неалкогольной жировой болезнью печени (НАЖБП) и сахарным диабетом 2 типа (СД2). Применяемые сегодня методы диагностики имеют ряд недостатков, связанных с инвазивностью, высокой стоимостью либо недостаточной чувствительностью и специфичностью. В связи с этим поиск новых неинвазивных маркеров фиброза печени остается актуальной задачей.

ЦЕЛЬ

ЦЕЛЬ. Установить диагностическую значимость определения в сыворотке крови ростового фактора дифференцировки-15 (GDF-15), ассоциированного с микрофибриллами белка-4 (MFAP-4), альфа1 цепи коллагена IV типа (COL4alpha1), Mac-2 связывающего белка (M2BPGI) и хрящевого гликопротеина-40 (YKL-40) как потенциальных биомаркеров фиброза печени у больных СД2 с НАЖБП.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. Проведено одноцентровое поперечное наблюдательное исследование. Обследовано 74 пациента, 23 мужчины и 51 женщина в возрасте от 18 до 74 лет. В качестве референсного метода диагностики фиброза печени применялась фиброэластометрия. Проводилась оценка неинвазивных индексов фиброза APRI и fib-4. Концентрации GDF-15, MFAP-4, COL4alpha1, M2BPGI и YKL-40 в сыворотке крови определяли методом иммуноферментного анализа. Для оценки чувствительности и специфичности сывороточных маркеров в диагностике фиброза печени применяли ROC-анализ.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. Фиброз печени 1-й стадии верифицирован у 16 человек, 2-й стадии — у 12, 3-й стадии — у 7, 4-й стадии — у 19 человек. Больные с выраженным фиброзом печени (стадии 3–4) по сравнению с больными без выраженного фиброза (стадии 0–2) имели более высокие уровни GDF-15 (p=0,003), COL4alpha1 (p=0,007) и YKL-40 (p=0,04). У больных с фиброзом печени стадии 1–2 выявлены более высокие уровни COL4alpha по сравнению с больными без признаков фиброза (p=0,02). Значимых различий в уровне MFAP-4 и M2BPGI между больными с различной выраженностью фиброза не установлено. По данным ROC-анализа, GDF-15, COL4alpha1 и YKL-40 обладают диагностической ценностью в выявлении выраженного фиброза печени, сопоставимой с таковой индексов APRI и fib-4.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. GDF-15, COL4alpha1 и YKL-40 могут рассматриваться как перспективные неинвазивные маркеры фиброза печени у больных СД2 с НАЖБП.

BACKGROUND

BACKGROUND: The diagnosis of liver fibrosis is an important task in the management of patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The currently used diagnostic methods have a number of disadvantages such as invasiveness and high cost, or insufficient sensitivity and specificity. Therefore, the search for new non-invasive markers of liver fibrosis remains an actual challenge.

AIM

AIM: To assess a diagnostic value of serum growth differentiation factor-15 (GDF-15), microfibril-associated glycoprotein 4 (MFAP-4), collagen type IV alpha1 (COL4alpha1), Mac-2 binding protein (M2BPGI) and chitinase-3-like protein 1 (YKL-40) as markers of liver fibrosis in patients with type 2 diabetes and NAFLD.

MATERIALS AND METHODS

MATERIALS AND METHODS: A single center cross-sectional observational study was performed. The study included 74 patients, 23 men and 51 women, aged 18 to 74 years. Liver elastography was used as reference method for the fibrosis evaluation. APRI and fib-4, non-invasive fibrosis indices, were assessed. Serum concentrations of GDF-15, MFAP-4, COL4alpha1, M2BPGI, and YKL-40 were determined by ELISA. ROC analysis was used to evaluate the sensitivity and specificity of serum markers for the diagnosis of the liver fibrosis.

RESULTS

RESULTS: Liver fibrosis stage 1 was verified in 16 subjects, stage 2 in 12, stage 3 in 7, and stage 4 in 19. Patients with advanced liver fibrosis (stages 3–4), compared with those without severe fibrosis (stages 0–2), had higher levels of GDF-15 (p=0.003), COL4alpha1 (p=0.007), and YKL-40 (p=0.04). Patients with stage 1-2 liver fibrosis had higher levels of COL4alpha compared to those without any signs of fibrosis (p=0.02). There were no significant differences in the level of MFAP-4 and M2BPGI between patients with different severity of fibrosis. According to the ROC analysis, GDF-15, COL4alpha1 and YKL-40 have diagnostic value in the detection of severe liver fibrosis comparable to that of the APRI and fib-4 indices.

CONCLUSION

CONCLUSION: GDF-15, COL4alpha1 and YKL-40 could be considered as promising non-invasive markers of liver fibrosis in patients with type 2 diabetes and NAFLD.

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