Zhongguo quanke yixue (May 2023)
Effects of Dapagliflozin on the Expression of MicroRNA-423-5p and Cardiac Function in Patients with Type 2 Diabetes Mellitus and Chronic Heart Failure
Abstract
Background There are numerous patients with diabetes complicated with heart failure. Dapagliflozin is a new hypoglycemic drug that has been used for heart failure according to guideline recommendation, however, its mechanism of improving heart function has not been fully defined. Objective To study the effects of dapagliflozin on the expression of plasma miRNA-423-5p and cardiac function in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) . Methods Fifty patients with T2DM complicated with CHF admitted to the 960th Hospital of PLA from April 1 to November 30, 2021 were enrolled and randomly divided into dapagliflozin group (n=25) and control group (n=25) . Both groups received the same treatment for six months except that dapagliflozin group received dapagliflozin 10 mg/d per day, and the control group received other hypoglycemic drugs. They were compared to healthy physical examinees with normal cardiac function (healthy group, n=25) . Basic data of the patients were collected through the electronic medical record system, including age, sex, smoking history, hypertension, blood pressure level, body mass index (BMI) , blood lipid, blood glucose, creatinine (Cr) , amino-terminal pro-B-type natriuretic peptide precursor (NT-proBNP) , alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , NYHA class, results of cardiac color ultrasound and drug combination. Blood samples were collected for the detection of miRNA-423-5p. A six-month follow-up was given to the patients with the time of first administration of dapagliflozin after inclusion as the starting point, during which patients' cardiac function indices and miRNA-423-5p were measured and collected at the end of four weeks of treatment, and their cardiac function indices, blood pressure level, ALT, AST, and Cr were measured at six months of treatment. Pearson correlation analysis or Spearman rank correlation analysis was used to analyze the correlation between miRNA-423-5p expression level and cardiac function indices of the patients. Results After 6 months of intervention, left ventricular ejection fraction (LVEF) , stroke output (SV) and left ventricular short-axis shortening rate (LVFS) in daglizin group were higher than those in control group, while left ventricular end-diastolic diameter (LVEDD) was lower than those in control group (P<0.05) . After 4 weeks and 6 months of intervention, LVEDD in 2 groups was lower than before intervention, while LVEF, SV and LVFS in 2 groups were higher than before intervention (P<0.05) . After 4 weeks of intervention, the level of NT-proBNP and miRNA-423-5p in Dagliegine group was lower than that in control group (P<0.05) , the level of NT-proBNP and miRNA-423-5p in two groups after intervention was lower than that before intervention in the same group (P<0.05) . The results of correlation analysis showed that the expression level of miRNA-423-5p was positively correlated with the level of NT-proBNP (rs=0.609, P<0.05) , and negatively correlated with the level of LVEF (r=-0.406, P<0.05) . Conclusion Dapagliflozin could improve cardiac function, reduce the levels of NT-proBNP and LVEDD, and increase the levels of LVEF, SV and LVFS in patients with T2DM and CHF, and the mechanism of action may be related to its regulation of the expression of plasma miRNA-423-5p .
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