- 學位論文
Empagliflozin對第二型糖尿病病患心臟功能與脂肪心及瀰漫性纖維化之探討
Effect of Empagliflozin on Cardiac Function, Adiposity and Diffuse Fibrosis in Patients with Type 2 Diabetic Mellitus
摘要
Empagliflozin，作為一個鈉-葡萄糖共同轉運蛋白抑制劑(sodium-glucose cotransporter 2 inhibitor, SGLT2 inhibitor)，可以在糖尿病患者上顯著改善心血管預後，主要在於改善心臟衰竭的死亡率及再住院率。然而，empagliflozin如何改善心臟衰竭其機制尚未明瞭。於是我們提出假說，empagliflozin也許可以對於心臟功能，心臟結構，以及心臟脂肪化，與心肌瀰漫性纖維化，有幫助的效果。 這個前瞻性研究從2017年06月01日至2018年11月31日，於國立臺灣大學醫學院附設醫院，共收案35位第二型糖尿病病人，其中48.6%為男性，平均年齡63.5 ± 9.7歲。所有受試者皆接受6個月的empagliflozin 25毫克/天或12.5毫克/天的治療，並且遵循糖尿病用藥指引及血糖控制穩定。所有受試者在接受empagliflozin之前以及之後，皆分別接受一次心臟核磁共振的檢查。在心臟核磁共振的檢查中，左心室的功能和結構將會被定量化，此外，心臟的脂肪化程度(cardiac adiposity)會以心包膜脂肪(pericardial fat)以及心臟內脂肪(intracardiac triglyceride) 計算表現。對於心臟瀰漫性纖維化(diffuse fibrosis)程度，會間接以細胞外容量(extracellular volume, ECV) 來做為代表。在這份資料的統計方式為成對t檢定(paired t test)以及向前式多變項線性迴歸分析(stepwise multiple linear regression analysis)。 我們的分析結果發現，在這些糖尿病病患中，在接受empagliflozin六個月後，左心室功能以及結構並沒有顯著的改變，在心臟脂肪化以及瀰漫性纖維化的程度指標在empagliflozin治療前後亦沒有達到統計上顯著差異的改變。對於臨床指標，只有收縮壓明顯平均下降6.4毫米汞柱(p=0.013)。向前式多變項線性迴歸分析發現當糖尿病患者基礎狀態的心臟核磁共振結果的參數越差時，對empagliflozin治療後所能夠獲得的心臟功能的改善越顯著。當糖尿病患者的脂肪心越嚴重時，心臟內的脂肪化程度越高，在接受empagliflozin後，心臟脂肪化下降的程度會越明顯(p<0.001)。心包膜脂肪的改變量亦與基礎心包膜脂肪量成顯著反比，意即，當糖尿病患者的心包膜脂肪量越多，在接受empagliflozin治療後，心包膜脂肪量會下降得更明顯(p<0.001)。對於瀰漫心肌纖維化的程度也與基礎瀰漫心肌纖維化程度，基礎左心室收縮功能，成反比顯著相關(p<0.001)，以及左心室質量改變量成顯著相關(p=0.002)。 在這個研究裡，整體而言，六個月療程的empagliflozin雖然沒有顯著改變第二型糖尿病病患的左心室功能，左心室結構，心臟脂肪化和瀰漫纖維化程度，但是我們發現在心臟功能越差的病患使用empagliflozin之後，所能夠改善的左心室的基質(substrate)以及結構越顯著。
並列摘要
Introduction: Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, significantly improves the cardiovascular outcomes in diabetic patients. However, the mechanism is still unclear. We hypothesized that empagliflozin might have beneficial effects on the cardiac function, structure as well as cardiac adiposity and myocardial diffuse fibrosis. Methods: The prospective study enrolled a total of 35 patients (48.6% male, age 63.5 ± 9.7) with type 2 diabetic mellitus (T2DM) from June 01, 2017, to November 31, 2018, at National Taiwan University Hospital. The subjects received a 6 month of SGLT2 inhibitor (empagliflozin 25 mg/d or 12.5 mg/d), on top of a stable oral hypoglycemic treatment. All enrolled patients received cardiac magnetic resonance imaging (CMRI) before and after empagliflozin treatment. The left ventricular (LV) function and structure were quantified by cine CMRI. The cardiac adiposity was presented as pericardial fat and intracardiac triglyceride (TG) content while the myocardial diffuse fibrosis was by extracellular volume (ECV). The statistical signifcance of the parameter changes were assessed by using paired t test and stepwise multiple linear regression analysis. Result: The results showed that there were no significant differences in LV function and structure changes. The cardiac adiposity and diffuse fibrosis indices were also not different before and after empagliflozin treatment. For clinical parameters, only a significant decrease in systolic blood pressure for 6.4 mmHg was found (p=0.013), Stepwise multiple linear regression analysis revealed that worse baseline MRI parameters were asssociated with better improvment. The decrease of intracardiac TG content was inversely associated with the baseline intracardiac TG content (p<0.001). The change of pericardial fat was negatively correlated to the baseline pericardial fat (p<0.001) and the change of ECV (p=0.028). The change of ECV was inversely associated with baseline ECV (p<0.001), baseline LVEF (p<0.001), and the change of LV mass index (p=0.020). Conclusion: In this study, we demonstrated that overall, a 6-month empagliflozin treatment did not show a sigifnicant improvement in the LV function, structure, adiposity and diffuse fibrosis in patients with T2DM. We also found that the beneficial effects of empagliflozin treatment might be more evident in patients with worse baseline LV substrate and structure.