Effects of Sitagliptin on cardiac diastolic function and myocardial fibrosis in patients with diabetes mellitus
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摘要: 目的:探讨西格列汀对糖尿病患者左室舒张功能及心肌纤维化的影响。方法:纳入新诊断为2型糖尿病且心脏收缩功能正常的患者117例, 随机分为西格列汀组 (58例) 和非西格列汀组 (59例)。西格列汀组单独服用西格列汀或西格列汀联合其他口服降糖药, 非西格列汀组单独或联合应用除DPP4抑制剂以外的其他口服降糖药。一级终点为:全因死亡, 心源性死亡, 心脏收缩功能不全, 新发心肌梗死, 心绞痛;二级终点为:治疗前及治疗后12个月超声心动图及心脏磁共振显示心脏舒张功能变化。比较治疗前及治疗后3、6、12个月时空腹血糖 (FBG)、糖化血红蛋白 (HbA1C)、B型脑钠肽 (BNP)、组织金属蛋白酶抑制剂-1 (TIMP-1)、半乳糖凝集素-3 (Gal-3) 等指标变化。结果:超声心动图显示西格列汀组E/A、DT、E/E'和左心房容积指数显著改善 (均P<0.05)。心脏磁共振显示西格列汀组的高峰充盈率 (PFR)、高峰充盈时间 (TPFR) 以及T1弛豫时间有明显改善 (均P<0.05)。和非西格列汀组相比, 西格列汀组BNP与Gal-3水平较基线水平显著降低, TIMP-1水平显著升高 (均P<0.05)。结论:西格列汀可显著延缓糖尿病患者的左室舒张功能不全和心肌僵硬度的发生发展。Abstract: Objective: To illustrate effects of Sitagliptin on left ventricular diastolic function and myocardial fibrosis in patients with diabetes mellitus.Method: A total of 117 patients who were newly diagnosed with 2 type diabetes mellitus and had a normal cardiac systolic function were included and randomly divided into Sitaglipti group (n=58) and non-Sitaglipti group (n=59).Patients in Sitaglipti group received Sitagliptin either alone or in combination with any other oral hypoglycemic medications, while patients in non-Sitaglipti group received other oral hypoglycemic medications excluding DPP4 i.Primary endpoints included all cause of death, heart failure, new myocardial infarction and unstable angina pectoris.Secondary endpoints included changes of cardiac diastolic function measured by echocardiography and cardiac magnetic resonance before and after 12 months of treatment.Fast blood glucose (FBG), glycosylated hemoglobin A1 C (HbA1 C), B-type natriuretic peptides (BNP), tissue inhibitor metalloproteinase-1 (TIMP-1) and galectin-3 (Gal-3) were measured before and after 3, 6 and 12 months of treatment.Result: Echocardiography showed that E/A, DT, E/E'and left atrial volume index in Sitagliptin group were significantly improved (all P<0.05).Cardiac magnetic resonance showed that peak filling rate (PFR), time of peak filling rate (TPFR) and T1 relaxation time in Sitagliptin group were significantly improved (all P<0.05).Compared with non-sitagliptin group, BNP and Gal-3 levels were significantly lower while TIMP-1 level was significantly higher than baseline levels (all P<0.05).Conclusion: Sitagliptin significantly postpone left ventricular diastolic dysfunction and myocardial stiffness in patients with diabetes mellitus.
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Key words:
- Sitagliptin /
- diabetes mellitus /
- diastolic function /
- myocardial fibrosis
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[1] Barouch LA, Gao D, Chen L, et al.Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survivalin murine models of obesity[J].Circ Res, 2006, 98 (1):119-124.
[2] Brownlee M.The pathobiology of diabetic complications a unifying mechanism[J].Diabetes, 2005, 54 (6):1615-1625.
[3] Giacco F, Brownlee M.Oxidative stress and diabetic complications[J].Cir Res, 2010, 107 (9):1058-1070.
[4] Lacombe VA, Viatchenko-Karpinski S, Terentyev D, et al.Mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes[J].Am J Physiol Regul Integr Comp Physiol, 2007, 293 (5):R1787-R1797.
[5] Taegtmeyer H, McNulty P, Young ME.Adaptation and maladaptation of the heart in diabetes:Part I general concepts[J].Circulation, 2002, 105 (14):1727-1733.
[6] Young ME, McNulty P, Taegtmeyer H.Adaptation and maladaptation of the heart in diabetes:Part II potential mechanisms[J].Circulation, 2002, 105 (15):1861-1870.
[7] Patil HR, Al Badarin FJ, Al Shami HA, et al.Meta-analysis of effect of dipeptidyl peptidase-4inhibitors on cardiovascular risk in type 2diabetes mellitus[J].Am J Cardiol, 2012, 110 (6):826-833.
[8] Scheller NM, Mogensen UM, Andersson C, et al.Allcause mortality and cardiovascular effects associated with the DPP-IV inhibitor sitagliptin compared with metformin, a retrospective cohort study on the Danish population[J].Diabetes Obes Metab, 2014, 16 (3):231-236.
[9] Eurich DT, Simpson S, Senthilselvan A, et al.Comparative safety and effectiveness of sitagliptin in patients with type 2diabetes:retrospective population based cohort study[J].BMJ, 2013, 346:f2267.
[10] Weir DL, McAlister FA, Senthilselvan A, et al.Sitagliptin use in patients with diabetes and heart failure:apopulation-based retrospective cohort study[J].JACC Heart Fail, 2014, 2 (6):573-582.
[11] Hamdani N, Hervent AS, Vandekerckhove L, et al.Left ventricular diastolic dysfunction and myocardial stiffness in diabetic mice is attenuated by inhibition of dipeptidyl peptidase 4[J].Cardiovasc Res, 2014, 104 (3):423-431.
[12] Lang RM, Biering M, Devereux RB, et al.Recommendations for chamber quantification:A report from the American society of echocardiography's guidelines and standards committee and the chamber quantification writing group, developed in conjunction with the European association of echocardiography, a branch of the European society of cardiology[J].J Am Soc Echocardiogr, 2005, 18 (12):1440-1463.
[13] Quinones MA, Otto CM, Stoddard M, et al.Recommendations for quantification of Doppler Echocardiography:A report from the Doppler Quantification task force of the nomenclature and standards committee of the American Society of Echocardiography[J].J Am Soc Echocardiogr, 2002, 15 (2):167-184.
[14] Go AS, Mozaffarian D, Roger VL, et al.Heart disease and stroke statistics-2013update:a report from the American Heart Association[J].Circulation, 2013, 127 (1):e6-e245.
[15] Ellims AH, Shaw JA, Stub D, et al.Diffuse myocardial fibrosis evaluated by post-contrast T1 mapping correlates with left ventricular stiffness[J].J Am Coll Cardiol, 2014, 63 (11):1112-1118.
[16] Ng AC, Auger D, Delgado V, et al.Association between diffuse myocardial fibrosis by cardiac magnetic resonance contrast-enhanced T1 mapping and subclinical myocardial dysfunction in diabetic patients a pilot study[J].Circ Cardiovasc Imaging, 2012, 5 (1):51-59.
[17] Weir RA, Petrie CJ, Murphy CA, et al.Galectin-3and cardiac function in survivors of acute myocardial infarction[J].Circ Heart Fail, 2013, 6 (3):492-498.
[18] 邓文浩, 李树仁, 张跃华, 等.Galectin-3拮抗剂-MCP对缺血性心功能不全的作用[J].临床心血管病杂志, 2017, 33 (6):554-559.
[19] de Boer RA, Lok DJ, Jaarsma T, et al.Predictive value of plasma galectin-3levels in heart failure with reduced and preserved ejection fraction[J].Ann Med, 2011, 43 (1):60-68.
[20] Lok DJ, Lok SI, Bruggink-Andréde la Porte PW, et al.Galectin-3is an independent marker for ventricular remodeling and mortality in patients with chronic heart failure[J].Clin Res Cardiol, 2013, 102 (2):103-110.
[21] Liu H, Pan H, Yang H, et al.LIM mineralization protein-1 suppresses TNF-α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression[J].J Orthop Res, 2015, 3 (3):294-303.
[22] Graham CA, Chan RW, Chan DY, et al.Matrix metalloproteinase 9mRNA:an early prognostic marker for patients with acute stroke[J].Clin Biochem, 2012, 45 (4-5):352-355.
[23] 蔡海荣, 黄玉萍, 袁康.灯盏细辛注射液对动脉硬化家兔脂代谢、内皮功能及MMP-9/TIMP-1表达的影响[J].临床心血管病杂志, 2017, 33 (10):1000-1003.
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