Effect of SGLT-2 (sodium-glucose cotransporter 2) inhibitors on cardiac remodelling correlated with cyclophilin a in type-2 diabetes mellitus patients without structural heart disease

Purpose: Sodium-Glucose Cotransporter 2 Inhibitor drugs have been used in the treatment of diabetes. Through the data obtained in this study, it was aimed to correlate Sodium-Glucose Cotransporter 2 inhibitors with Cyclophilin-A and diabetic biochemical markers, which had not taken place in the literature before, and to display their impact on Cyclophilin-A and echocardiography-guided cardiac remodelling in patients using Sodium-Glucose Cotransporter 2 Inhibitor. Material/Method: The demographic characteristics (age, gender, height, weight, body mass index, waist and hip circumferences), systolic and diastolic pressures and body fat percentages of the patients were recorded. Biochemical markers of diabetes, fasting plasma glucose, HbA1c, urea, creatinine markers, marker of vascular inflammation, Cyclophilin-A, marker of cardiac vascular disease, echocardiography markers were checked as laboratory parameters. These markers were checked again 24 months later. Venous blood samples were taken from the patients in sitting position while they were in relaxation period following 8 hours of fasting. 3 cc blood samples for cyclophilin-A level were taken into the tubes containing EDTA and in 30 minutes they were centrifuged for 7 minutes at 2500 g. Having been separated, the plasma was taken into a new tube and stored at -80 °C until the day when they would be measured in order to perform an immunological test with a biochemical Elisa kit. During the echocardiography examination, M-mode, two-dimensional 2D, Doppler echocardiography, coloured Doppler, Continue Wave Doppler (CWD), Pulse Wave Doppler (PWD), Pulse Wave Tissue Doppler (PWDD) evaluations were conducted. The ejection fraction which shows left ventricular systolic function, Tricuspid Annular Plane Systolic Excursion (TAPSE) which shows right ventricular systolic function, right ventricular S value, Septal E and Lateral E values which show left ventricular diastolic functions were checked. Findings: The baseline and 24th-week findings of 38 patients who were included in the study were considered and it was observed that weight, body mass index, body fat percentage, diastolic blood pressure values were statistically and significantly lower at 24th week than at baseline (p<0.001;p<0.001;p<0.001;p=0.006, respectively). Similarly, fasting plasma glucose, HbA1C, urea and creatinine values were found to be statistically and significantly lower at 24th week than at baseline (p<0.001;p<0.001; p<0.001; p<0.001, respectively). No significant correlation was found between baseline cyclophilin-A values and baseline parameters (p>0.05). The baseline and 24th-week findings showed that cyclophilin-A values statistically and significantly lower at 24th week than at baseline (p<0.001). A negative correlation was observed between Cyclophilin-A value and weight, body mass index and HbA1c. Echocardiography was performed to the patients at baseline and 24th week. It was found that 24th-week Lateral E and Septal E values were lower than treatment baseline values (p=0.044; p=0.013, respectively). While a negative moderate correlation was observed between 24th-week Cyclophilin-A values and right ventricular S wave measurement (r=-0.336); no significant correlation was found between 24th-week cyclophilin-A values and related parameters (p>0.05). Sodium-Glucose Cotransporter 2 Inhibitor sub-group analysis was performed. When dapaglifozin and empaglifozin were compared to the parameters closely, it was determined that the change in the weight and body fat percentages of the patients who used empaglifozin was more than of the patients who used dapaglifozin (p=0.013; p=0.010, respectively). Their effects on systolic and diastolic blood pressures, fasting plasma glucose, HbA1c, Cyclophilin-A and echocardiography parameters were similar in both medication. Conclusion: As a group effect, sodium-Glucose Cotransporter 2 Inhibitor drugs reduced the levels of weight, fasting blood glucose, blood pressure and inflammatory indicator level compared to the baseline levels. It is believed that Sodium-Glucose Cotransporter 2 Inhibitor drugs would affect inflammatory indicator negatively by regulating the blood pressure level through ensuring blood glucose level and would manage to prevent cardiac damage in patients without structural heart disease. Keywords: HbA1c, SGLT2i, Type 2 DM, body weight, ECO, CypA