Effect of Empagliflozin on Cardiac Function, Adiposity, and Diffuse Fibrosis in Patients with Type 2 Diabetes Mellitus
Effect of Empagliflozin on Cardiac Function, Adiposity, and Diffuse Fibrosis in Patients with Type 2 Diabetes Mellitus
复制标题
DOI：
10.1038/s41598-019-51949-5
复制
发表时间：
2019-10-25
影响因子：
4.6
通讯作者：
Yang, Wei-Shiung
中科院分区：
文献类型：
--
作者：
Hsu, Jung-Chi;Wang, Chih-Yuan;Yang, Wei-Shiung
钠-葡萄糖共转运体2(SGLT2)抑制剂依帕格列夫秦显著改善糖尿病患者的心血管结局；然而，其机制尚不清楚。我们推测依帕格列酮可能对心脏功能、结构、肥胖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从2017年6月1日至2018年11月31日的35名2型糖尿病(T2 DM)患者(48.6%的男性，年龄63.5+/-9.7岁)。除了口服稳定的降糖治疗外，患者还接受SGLT2抑制剂(依帕格列酮25或12.5 mg/d)治疗6个月。所有患者在依帕格列酮治疗前后均进行心脏磁共振成像(CMRI)检查。采用CMRI电影成像技术定量测量左心室(LV)功能和结构。心脏肥胖症是根据心包脂肪和心内甘油三酯含量来定义的，而心肌弥漫性纤维化是通过细胞外体积(ECV)来指示的。用配对t检验和逐步多元线性回归分析参数变化的统计学意义。两组在左心室功能和结构改变方面无明显差异。治疗前后心脏肥胖症和弥漫性纤维化指标也无明显差异。在临床参数方面，仅观察到显著的收缩压下降(6.4mmHg)(p=0.013)。逐步多元线性回归显示，基线MRI参数越差，改善越好。心内甘油三酯含量下降与基线心内甘油三酯含量呈负相关(p<；0.001)。心包脂肪变化与基础心包脂肪(p<；0.001)和体外循环血容量变化(p=0.028)呈负相关。ECV改变与基线ECV(p<；0.001)、基线LV射血分数(p<；0.001)和LV质量指数改变(p=0.020)呈负相关。这项研究表明，6个月的依帕格列酮治疗并没有显著改善T2 DM患者的左心功能、结构、肥胖度和弥漫性纤维化。此外，依帕格列酮治疗的有益效果可能在基础左心室基质和结构较差的患者中更为明显。
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.