MicroRNAs as targets and biomarkers of myocardial fibrosis in patients with type 1 diabetes mellitus

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

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: 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: 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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