請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72560
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林亮宇(Lian-Yu Lin) | |
dc.contributor.author | Jung-Chi Hsu | en |
dc.contributor.author | 許容綺 | zh_TW |
dc.date.accessioned | 2021-06-17T07:00:55Z | - |
dc.date.available | 2020-08-26 | |
dc.date.copyright | 2019-08-26 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-08-01 | |
dc.identifier.citation | Boyer JK, Thanigaraj S, Schechtman KB, Pérez JE: Prevalence of ventricular diastolic dysfunction in asymptomatic, normotensive patients with diabetes mellitus. The American Journal of Cardiology 2004;93:870-875
Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB: Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens 2014;8:262-275 e269 Doesch C, Haghi D, Flüchter S, Suselbeck T, Schoenberg SO, Michaely H, Borggrefe M, Papavassiliu T: Epicardial adipose tissue in patients with heart failure. Journal of Cardiovascular Magnetic Resonance 2010;12:40 Ferrannini E, Mark M, Mayoux E: Response to Comment on Ferrannini et al. Diabetes Care 2016;39:1108–1114. Comment on Mudaliar et al. Diabetes Care 2016;39:1115–1122. Diabetes Care 2016;39:e196-e197 Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, Broedl UC, Woerle H-J: Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. Journal of Clinical Investigation 2014;124:499-508 Gilbert RE, Connelly K, Kelly DJ, Pollock CA, Krum H: Heart failure and nephropathy: catastrophic and interrelated complications of diabetes. Clin J Am Soc Nephrol 2006;1:193-208 Hakkarainen KNMGrMOPiJLA: Cardiac steatosis and left ventricular function in men with metabolic syndrome. Journal of Cardiovascular Magnetic Resonance 2013; 15:103 Hammer S, Snel M, Lamb HJ, Jazet IM, van der Meer RW, Pijl H, Meinders EA, Romijn JA, de Roos A, Smit JW: Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function. J Am Coll Cardiol 2008;52:1006-1012 Inzucchi SE, Kosiborod M, Fitchett D, Wanner C, Hehnke U, Kaspers S, George JT, Zinman B: Improvement in Cardiovascular Outcomes With Empagliflozin Is Independent of Glycemic Control. Circulation 2018;138:1904-1907 Iacobellis G, Ribaudo MC, Assael F, Vecci E, Tiberti C, Zappaterreno A, Di Mario U, Leonetti F: Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk. J Clin Endocrinol Metab 2003;88:5163-5168 Konishi M, Sugiyama S, Sugamura K, Nozaki T, Matsubara J, Akiyama E, Utsunomiya D, Matsuzawa Y, Yamashita Y, Kimura K, Umemura S, Ogawa H: Accumulation of pericardial fat correlates with left ventricular diastolic dysfunction in patients with normal ejection fraction. Journal of Cardiology 2012;59:344-351 Korosoglou G, Humpert PM, Ahrens J, Oikonomou D, Osman NF, Gitsioudis G, Buss SJ, Steen H, Schnackenburg B, Bierhaus A, Nawroth PP, Katus HA: Left ventricular diastolic function in type 2 diabetes mellitus is associated with myocardial triglyceride content but not with impaired myocardial perfusion reserve. Journal of Magnetic Resonance Imaging 2012;35:804-811 Kim JW, Lee YJ, You YH, Moon MK, Yoon KH, Ahn YB, Ko SH: Effect of sodium-glucose cotransporter 2 inhibitor, empagliflozin, and alpha-glucosidase inhibitor, voglibose, on hepatic steatosis in an animal model of type 2 diabetes. J Cell Biochem 2018;Nov26 Lin L-Y, Wu C-K, Juang J-MJ, Wang Y-C, Su M-YM, Lai L-P, Hwang J-J, Chiang F-T, Tseng W-YI, Lin J-L: Myocardial Regional Interstitial Fibrosis is Associated With Left Intra-Ventricular Dyssynchrony in Patients With Heart Failure: A Cardiovascular Magnetic Resonance Study. Scientific Reports 2016;620711 Lin LY, Su MY, Pham VT, Tran TT, Wang YH, Tseng WY, Lo MT, Lin JL: Endocardial Remodeling in Heart Failure Patients with Impaired and Preserved Left Ventricular Systolic Function--A Magnetic Resonance Image Study. Sci Rep 2016;6:20868 Liedtke AJ, DeMaison L, Eggleston AM, Cohen LM, Nellis SH: Changes in substrate metabolism and effects of excess fatty acids in reperfused myocardium. Circulation Research 1988;62:535-42 Mudaliar S, Alloju S, Henry RR: Can a Shift in Fuel Energetics Explain the Beneficial Cardiorenal Outcomes in the EMPA-REG OUTCOME Study? A Unifying Hypothesis. Diabetes Care 2016;39:1115-1122 Milwidsky A, Maor E, Kivity S, Berkovitch A, Zekry SB, Tenenbaum A, Fisman EZ, Erez A, Segev S, Sidi Y, Goldenberg I, Kuperstein R: Impaired fasting glucose and left ventricular diastolic dysfunction in middle-age adults: a retrospective cross-sectional analysis of 2971 subjects. Cardiovascular Diabetology 2015;14:119 McGavock JM, Lingvay I, Zib I, Tillery T, Salas N, Unger R, Levine BD, Raskin P, Victor RG, Szczepaniak LS: Cardiac Steatosis in Diabetes Mellitus. Circulation 2007;116:1170-1175 Ng AC, Delgado V, Bertini M, van der Meer RW, Rijzewijk LJ, Hooi Ewe S, Siebelink HM, Smit JW, Diamant M, Romijn JA, de Roos A, Leung DY, Lamb HJ, Bax JJ: Myocardial steatosis and biventricular strain and strain rate imaging in patients with type 2 diabetes mellitus. Circulation 2010;122:2538-2544 Su M-YM, Lin L-Y, Tseng Y-HE, Chang C-C, Wu C-K, Lin J-L, Tseng W-YI: CMR-Verified Diffuse Myocardial Fibrosis Is Associated With Diastolic Dysfunction in HFpEF. JACC: Cardiovascular Imaging 2014;7:991-997 Qaseem A, Barry MJ, Humphrey LL, Forciea MA: Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline Update From the American College of Physicians. Annals of Internal Medicine 2017;166:279-290 Rosenstein R HA: Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine 2016;374:1092-1094 Rijzewijk LJ, van der Meer RW, Smit JW, Diamant M, Bax JJ, Hammer S, Romijn JA, de Roos A, Lamb HJ: Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol 2008;52:1793-1799 Ridderstråle M, Andersen KR, Zeller C, Kim G, Woerle HJ, Broedl UC, Diabetes E-RHH-StiJTL, Endocrinology: Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2:691-700 Rosito GA, Massaro JM, Hoffmann U, Ruberg FL, Mahabadi AA, Vasan RS, O'Donnell CJ, Fox CS: Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation 2008;117:605-613 Seferovic PM, Paulus WJ: Clinical diabetic cardiomyopathy: a two-faced disease with restrictive and dilated phenotypes. Eur Heart J 2015;36:1718-1727, 1727a-1727c Sattar N, Fitchett D, Hantel S, George JT, Zinman B: Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME(R) trial. Diabetologia 2018;61:2155-2163 Škrtić M, Cherney DZI: Sodium–glucose cotransporter-2 inhibition and the potential for renal protection in diabetic nephropathy. Current Opinion in Nephrology and Hypertension 2015;24:96-103 Taylor AJ, Salerno M, Dharmakumar R, Jerosch-Herold M: T1 Mapping: Basic Techniques and Clinical Applications. JACC Cardiovasc Imaging 2016;9:67-81 Teupe C, Rosak C: Diabetic cardiomyopathy and diastolic heart failure – Difficulties with relaxation. Diabetes Research and Clinical Practice 2012;97:185-194 Verma S, Rawat S, Ho KL, Wagg CS, Zhang L, Teoh H, Dyck JE, Uddin GM, Oudit GY, Mayoux E, Lehrke M, Marx N, Lopaschuk GD: Empagliflozin Increases Cardiac Energy Production in Diabetes. JACC: Basic to Translational Science 2018;3:575-587 Verma S, Garg A, Yan AT, Gupta AK, Al-Omran M, Sabongui A, Teoh H, Mazer CD, Connelly KA: Effect of Empagliflozin on Left Ventricular Mass and Diastolic Function in Individuals With Diabetes: An Important Clue to the EMPA-REG OUTCOME Trial? Diabetes Care 2016;39:e212-e213 van der Meer RW, Rijzewijk LJ, de Jong HW, Lamb HJ, Lubberink M, Romijn JA, Bax JJ, de Roos A, Kamp O, Paulus WJ, Heine RJ, Lammertsma AA, Smit JW, Diamant M: Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation 2009;119:2069-2077 Wu CK, Tsai HY, Su MM, Wu YF, Hwang JJ, Lin JL, Lin LY, Chen JJ: Evolutional change in epicardial fat and its correlation with myocardial diffuse fibrosis in heart failure patients. J Clin Lipidol 2017;11:1421-1431 Wu CK, Tsai HY, Su MY, Wu YF, Hwang JJ, Tseng WY, Lin JL, Lin LY: Pericardial fat is associated with ventricular tachyarrhythmia and mortality in patients with systolic heart failure. Atherosclerosis 2015;241:607-614 Yan SVCDMAT: Late-Breaking Science Abstracts From the American Heart Association’s Scientific Sessions 2018 and Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2018. Circulation 2018;138:e751-e782 Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE: Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine 2015;373:2117-2128 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72560 | - |
dc.description.abstract | 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。 | zh_TW |
dc.description.abstract | 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. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T07:00:55Z (GMT). No. of bitstreams: 1 ntu-108-P06421017-1.pdf: 2461819 bytes, checksum: ab78826edc8219200ad96025c3c16e58 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iv 英文摘要 vi 碩士論文內容 第一章 緒論 1 第二章 研究方法與材料 3 2.1 實驗設計與族群 3 2.2 心臟核磁共振影像蒐集 3 2.3 心臟核磁共振影像分析 4 第三章 結果 6 第四章 討論 7 第五章 展望 10 第六章 論文英文簡述 (summary) 11 第七章 參考文獻 19 第八章 圖表 表1 24 表2 27 表3 29 圖1 30 圖2 31 | |
dc.language.iso | zh-TW | |
dc.title | 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 | zh_TW |
dc.title | Effect of Empagliflozin on Cardiac Function, Adiposity and Diffuse Fibrosis in Patients with Type 2 Diabetic Mellitus | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 楊偉勛(Wei-Shiung Yang),莊志明(Jyh-Ming Jimmy Juang) | |
dc.subject.keyword | empagliflozin,鈉-葡萄糖共同轉運蛋白抑制劑,糖尿病,脂肪心,心臟脂肪化,瀰漫性纖維化, | zh_TW |
dc.subject.keyword | empagliflozin,SGLT2 inhibitor,diabetes mellitus,cardiac steatosis,diffuse fibrosis, | en |
dc.relation.page | 31 | |
dc.identifier.doi | 10.6342/NTU201902358 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-08-01 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
顯示於系所單位: | 臨床醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-108-1.pdf 目前未授權公開取用 | 2.4 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。