Discussion
NAFLD, liver steatosis, ventricular arrhythmias, ASCVD, liver fibrosis, fibrosis, LV systolic dysfunction, hepatic steatosis, NALFD, T2DM
VENTRICULAR ARRHYTHMIA, CVD, LIVER STEATOSIS, CARDIAC DEATH, DIABETES MELLITUS, LIVER FIBROSIS, FIBROSIS, HEPATIC STEATOSIS, MYOCARDIAL DYSFUNCTION, ASCVD
Left ventricular ejection fraction (LVEF) is a central measure of global systolic function [It is also an independent predictor of CVD, cardiac death, and ventricular arrhythmias [In patients with diabetes mellitus, abnormal GLS may be a marker of subclinical LV systolic dysfunction, even in asymptomatic patients [In the present study, we showed that in patients with T2DM with NAFLD and without established ASCVD, liver fibrosis is associated with reduced GLS at baseline. Our results are in parallel with the CARDIA study [We also demonstrated that both empagliflozin and pioglitazone significantly improve liver fibrosis and ameliorate LV remodeling and subtle myocardial dysfunction. However, there was no statistically significant relationship between GLS, LSM, and CAP changes. The relatively small sample size and short duration of the study might act as interfering factors. Moreover, the changes in LSM could be partly related to changes in CAP. Nevertheless, improvement of cardiac structure and function in this study appear to be independent of the improvement of liver steatosis and fibrosis. The greater numerical improvement of GLS in the empagliflozin group compared to pioglitazone has a clinical importance. However, it did not reach the limit of statistical significance. This might be explained by low power of the study to detect statistical significance between the two groups.Using an animal model, Santos-Gallego et al. showed that empagliflozin in the non-diabetic model reduces LV remodeling and improves myocardial strain by decreasing neuro-hormonal activation. They suggested that the effects of empagliflozin are independent of its impact on glucose homeostasis [Empagliflozin improves cardiac energetics and metabolism and reduces LV remodeling by increasing the oxidation of free fatty acids, ketone bodies, and branched-chain amino acids [The present study demonstrates that pioglitazone improves liver fibrosis and ameliorates subclinical myocardial dysfunction. In addition, empagliflozin and pioglitazone improved diastolic function in our patients with T2DM and NALFD. We showed in our previous studies that empagliflozin effectively improves liver steatosis in patients with and without T2DM [In addition, Yoneda et al. evaluated the changes in hepatic steatosis after 24 weeks of pioglitazone and tofogliflozin treatment using MRI-PDFF. No significant differences were observed between the groups concerning relative changes from the baseline [We do have some limitations in our study. It was a single-center study with small number of patients. All patients were asked to follow lifestyle modification recommendations to control HbA1c as an interfering factor. However, although we managed lipid and glycemic control according to the standard guideline, the impact of other unmeasured confounders can never be overemphasized. In addition, we did not perform a liver biopsy as the gold standard method to evaluate liver steatosis and fibrosis.