Department of Internal Medicine, Division of Cardiology, Saint Mary's Hospital Luodong, Yilan, 26546, Taiwan.
Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, 10617, Taiwan.
Sci Rep. 2019 Oct 25;9(1):15348. doi: 10.1038/s41598-019-51949-5.
Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, significantly improves cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that empagliflozin might have beneficial effects on cardiac function, structure, adiposity, and myocardial diffuse fibrosis. This prospective study enrolled 35 patients (48.6% men, age 63.5 ± 9.7 years) with type 2 diabetes mellitus (T2DM) from June 1, 2017, to November 31, 2018. The patients received an SGLT2 inhibitor (empagliflozin 25 or 12.5 mg/d) for 6 months in addition to stable oral hypoglycaemic treatment. All patients underwent cardiac magnetic resonance imaging (CMRI) before and after empagliflozin treatment. Left ventricular (LV) function and structure were quantified using cine CMRI. Cardiac adiposity was defined based on pericardial fat and intracardiac triglyceride contents, whereas myocardial diffuse fibrosis was indicated by extracellular volume (ECV). The statistical significance of parameter changes was assessed using paired t-test and stepwise multiple linear regression. There were no significant differences in LV function and structure changes. Cardiac adiposity and diffuse fibrosis indices were also not different before and after empagliflozin treatment. Concerning clinical parameters, only a significant decrease in systolic blood pressure (by 6.4 mmHg) was observed (p = 0.013). Stepwise multiple linear regression revealed that worse baseline MRI parameters were associated with better improvements. Intracardiac triglyceride content decrease was inversely associated with baseline intracardiac triglyceride content (p < 0.001). Pericardial fat changes were negatively correlated with baseline pericardial fat (p < 0.001) and ECV changes (p = 0.028). ECV changes were inversely associated with baseline ECV (p < 0.001), baseline LV ejection fraction (p < 0.001), and LV mass index changes (p = 0.020). This study demonstrated that 6 months of empagliflozin treatment did not significantly improve the LV function, structure, adiposity, and diffuse fibrosis in patients with T2DM. Further, the beneficial effects of empagliflozin treatment might be more evident in patients with worse baseline LV substrate and structure.
恩格列净是一种钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂，可显著改善糖尿病患者的心血管结局；然而，其机制尚不清楚。我们假设恩格列净可能对心脏功能、结构、脂肪含量和心肌弥漫性纤维化有有益的影响。这项前瞻性研究纳入了 2017 年 6 月 1 日至 2018 年 11 月 31 日期间 35 名（48.6%为男性，年龄 63.5±9.7 岁）患有 2 型糖尿病（T2DM）的患者。这些患者在接受稳定的口服降糖治疗的基础上，额外接受 SGLT2 抑制剂（恩格列净 25 或 12.5mg/d）治疗 6 个月。所有患者在接受恩格列净治疗前后均接受心脏磁共振成像（CMRI）检查。采用电影 CMRI 定量左心室（LV）功能和结构。根据心包脂肪和心脏内甘油三酯含量定义心脏脂肪含量，而细胞外容积（ECV）则提示心肌弥漫性纤维化。采用配对 t 检验和逐步多元线性回归评估参数变化的统计学意义。在接受恩格列净治疗前后，LV 功能和结构变化无显著差异。心脏脂肪含量和弥漫性纤维化指数也没有差异。在临床参数方面，仅观察到收缩压显著下降（6.4mmHg，p=0.013）。逐步多元线性回归显示，基线 MRI 参数较差与改善幅度较大相关。心脏内甘油三酯含量下降与基线心脏内甘油三酯含量呈负相关（p<0.001）。心包脂肪变化与基线心包脂肪（p<0.001）和 ECV 变化（p=0.028）呈负相关。ECV 变化与基线 ECV（p<0.001）、基线 LV 射血分数（p<0.001）和 LV 质量指数变化（p=0.020）呈负相关。这项研究表明，在 T2DM 患者中，接受恩格列净治疗 6 个月并不能显著改善 LV 功能、结构、脂肪含量和弥漫性纤维化。此外，恩格列净治疗的有益效果在基线 LV 底物和结构较差的患者中可能更为明显。
