【作者】 闫阳妹；

【导师】 吴伟利； 傅向华；

【作者基本信息】 河北医科大学 ， 内科学， 2010， 硕士

【摘要】 目的:本文通过对比规律服用格列本脲和规律应用胰岛素或单纯饮食控制血糖的急性心肌梗死合并2型糖尿病患者心肌灌注情况及心律失常发生率,探讨格列苯脲可能对缺血心肌的不良效应,为更有效、更合理的治疗提供依据。方法:选择2008年2月至2009年12月于我科住院的冠心病急性心肌梗死合并2型糖尿病患者105例（男性60例,女性45例,平均年龄56.87±8.95岁）。所有患者符合WHO冠心病急性心肌梗死的诊断标准;符合WHO 2型糖尿病的诊断标准;依从性好能定期随访。排除标准:胰岛素依赖的糖尿病患者;原有严重瓣膜性心脏病,心肌病,心肌炎,心包炎,原发肺动脉高压者;明确诊断患有糖尿病性视网膜增值性病变患者;患有糖尿病神经病变及糖尿病肾病的患者（血肌酐>136μmol/L）;潜在的胃肠道出血、贫血、合并其他内分泌疾病或主要脏器疾病如严重肝肾功能不全者,恶性肿瘤患者。将105名入选患者根据既往治疗情况分为规律应用格列苯脲为试验组A组35例,应用胰岛素为对照组B组35例,饮食控制为空白对照组C组35例。所有患者入院后基础治疗均接受标准的抗血小板、抗凝治疗,皮下注射低分子肝素,并同时服用肠溶阿司匹林,氯吡格雷,血管紧张素转换酶抑制剂（ACEI）、他汀类调脂药物、硝酸酯类药物,酌情选用选择性β1受体阻滞剂,继续维持以往降糖治疗,A组应用格列苯脲（2.5mg-5mg,3/日,天津太平洋制药有限公司）;B组应用生物合成人胰岛素（诺和公司,25u-50u/日）;C组单纯饮食控制。每组患者收集详细临床资料,年龄、性别、体重指数、吸烟、饮酒、高血压、血脂、行心电图、心肌酶、肌钙蛋白I、肝肾功能、血常规、尿便常规、血脂、血糖、糖化血红蛋白、胰岛素及C肽释放、24小时尿白蛋白排泄率等、心功能分级,患者入院后七日行心脏超声明确心功能;全部患者择期行冠状动脉造影明确冠脉情况,并行冠状动脉支架植入术（PCI）,记录冠状动脉造影血管病变支数、病变程度、TIMI分级、支架类型等。三组患者均于术后3-5天内行动态心电图检查。稳定后出院,并于术后一个月复查,行单光子发射型计算机心肌断层显像（简称SPECT）,观察心肌缺血面积,平衡门控心血池显像（equilibrium radionuclide angiography,ERNA）观察左心室射血分数;所有数据均应用SPSS13.0软件包进行统计学处理,正态计量资料以均数±标准差表示,非正态计量资料用中位数表示,正态计量资料采用t检验,计量资料多组间比较采用方差分析,计数资料采用χ²检验,等级资料及非正态计量资料采用秩和检验,以P<0.05定为有统计学意义。结果:两组患者在性别、体重指数、吸烟、饮酒、高血压、服用药物、血常规、血脂、糖化血红蛋白、血糖、胰岛素、C-肽、肾功能、尿蛋白、心功能分级、冠脉造影病变情况、支架类型等方面比较无统计学差异。冠脉造影结果显示三组患者TIMI血流<TIMIⅢ级的患者比率有统计学差异,格列苯脲组冠脉血流<TIMIⅢ级的患者比率大于两对照组（48.57% vs 17.14% vs 20%,χ²=10.360, P=0.006）;其中A组比率高于B组,差异有统计学意义（P=0.010）;A组比率高于C组,差异有统计学意义（P=0.014）;B组、C组差异无统计学意义（P=0.759）。Holter结果显示,格列苯脲组室性心律失常发生率低于两对照组,差异有统计学意义,（22.86% vs 48.57% vs 51.54%,χ²=8.810, P=0.012）,两两比较A组发生率低于B组,差异有统计学意义（χ²=6.341, P=0.012）;A组发生率低于C组,差异有统计学意义（χ² = 7.529, P=0.006）;B组发生率低于C组,差异无统计学意义（χ²=0.057, P=0.881）。心律失常评分,格列苯脲组评分低于两对照组,差异有统计学意义（10 vs 25 vs 23,χ²=7.410, P=0.025）;其中A组评分低于B组,差异有统计学意义(χ²=6.991, P=0.008;A组评分低于C组,差异有统计学意义（χ²=5.915, P=0.015）;B组、C组差异无统计学意义（χ²=0.195, P=0.659）。静息状态下格列苯脲组患者出现缺血心肌节段高于两对照组,差异有统计学意义（380 vs 300 vs 302,χ²=11.396, P=0.003）,其中A组缺血心肌节段高于B组,差异有统计学意义（χ²=6.138, P=0.013）;A组缺血心肌节段高于C组,差异有统计学意义（χ²=11.221, P=0.001）;B组、C组差异无统计学意义（χ²=0.008, P=0.929 ）。静息无硝甘介入时格列苯脲组心肌^99mTc-MIBI摄取率低于两对照组,差异有统计学意义[48.35% vs（55.20±7.19）% vs 54.34%,χ²=15.268, P=0.000];两两比较,A组心肌^99mTc-MIBI摄取率低于B组,差异有统计学意义（χ²=12.668, P=0.000）;A组心肌^99mTc-MIBI摄取率低于C组,差异有统计学意义（χ²=9.042, P=0.003）;B组、C组差异无统计学意义（χ²=1.871, P=0.277）;硝酸甘油介入后格列苯脲组^99mTc-MIBI摄取率低于两对照组,差异有统计学意义（56.17% vs 65.7% vs 62.17%,χ²=11.627, P=0.003）,两两比较A组心肌^99mTc-MIBI摄取率低于B组,差异有统计学意义（χ²=9.544, P=0.002）;A组心肌^99mTc-MIBI摄取率低于C组,差异有统计学意义（χ²=6.648, P=0.010）;B组、C组差异无统计学意义（χ²=1.298, P=0.255）。A组硝酸甘油介入前^99mTc-MIBI摄取率低于硝酸甘油介入后,差异有统计学意义（48.35% vs 56.17%,χ²=5.159, P=0.000）;B组硝酸甘油介入前^99mTc-MIBI摄取率低于硝酸甘油介入后,差异有统计学意义[（55.20±7.19）% vs 65.7%,χ²=24.377, P=0.000];C组硝酸甘油介入前^99mTc-MIBI摄取率低于硝酸甘油介入后,差异有统计学意义（54.34% vs 62.17%,χ²=22.355, P=0.000）。格列苯脲组心肌缺血面积评分高于两对照组,差异有统计学意义（64 vs 46 vs 46,χ²=8.538, P=0.014<0.05）,其中A组心肌缺血面积评分高于B组,差异有统计学意义（χ²=5.873, P=0.015<0.017）;A组心肌缺血面积评分高于C组,差异有统计学意义（χ²=6.768, P=0.009<0.017）;B组、C组差异无统计学意义（P=0.969>0.05）。ERNA显示格列苯脲组左室射血分数低于两对照组,差异有统计学意义[53% v（s56.51±4.23）% vs 60%,χ²=21.479, P=0.000<0.05];A组左室射血分数低于B组,差异有统计学意义（P=0.001<0.017）;A组左室射血分数低于C组,差异有统计学意义（χ²=4.545, P=0.000<0.017 ）; B组、C组差异无统计学意义（P=0.033>0.017）。结论:1应用格列苯脲组患者心肌显像缺血面积高于胰岛素及饮食控制组,提示格列苯脲会增加急性心肌梗死合并2型糖尿病患者心肌缺血或梗死面积,并减低左心室收缩功能。2格列苯脲影响急性心肌梗死合并2型糖尿病的患者冠脉的TIMI血流。3格列苯脲对急性心肌梗死合并2型糖尿病的患者减少发生恶性心律失常的可能。更多还原

【Abstract】 Objective: To compare the myocardial perfusion conditions and the incidence of arrhythmias in patients with CHD and type 2 diabetes who taking glibenclamide or insulin regularly, to assess the adverse effects of glibenclamide on the myocardium, for investigating more effective and rational therapy.Methods: From June, 2008 and December, 2009, 105 consecutive patients (60 male and 45female, age 56.87±8.95 years) who with type 2 diabetes and coronary artery disease were enrolled into the study. All patients had clinical histories of acute myocardial infarction and losed the chance of thrombolysis and emergency PCI; Type 2 Diabetes were diagnosed according to the criterion of WHO; Patients were excluded for any of the following reasons: Insulin-dependent diabetes mellitus; The original severe valvular heart disease, cardiomyopathy, myocarditis, pericarditis, primary pulmonary hypertension; diabetic proliferative retinopathy assessed by an experienced ophthalmologist; diabetic neuropathy assessed by autonomic neuropathy tests or diabetic nephropathy (creatinine>136μmol/L); potential of gastrointestinal bleeding, anemias, and other endocrine or major organ diseases.Each patient was assigned to either insulin or glibenclamide group according to which treatment he accepted outside hospital regularly. The patients who took glibenclamide for group A, insulin for group B and diet for group C. All patients were admitted to hospital and subcutaneous inject low molecula heparin, while oral aspirin, clopidogrel, angiotensin-converting enzyme inhibitor (ACEI), statins, nitrates, If necessary, applied appropriate dose ofβ1-blockers. Collected the clinical informations of all patients in each group detailed, age, sex, body mass index, smoking, drinking, hypertension, hyperlipidemia, electrocardiogram, myocardial enzymes, cardiac troponin I, liver and kidney function, red cell, urine will be normal, blood lipids, blood glucose, glycated hemoglobin, insulin and C-peptide release, a 24-hour urinary albumin excretion, 7 days after myocardial infarction all patients took echocardiography to evaluate the condition of wall motion, ventricular wall thickness, ventricular diameter; 10 days after took selective coronary angiography and PCI, recorded the TIMI rank of the coronary flow lesion count, lesion extent, stents types, etc, took holter in the 3-5 days after operation. one month after PCI all patients took SPECT to evaluate the condition of myocardial perfusion, and ERNA for LVEF; All data are applied SPSS 13.0 for statistical analysis, Normal measurement data express to mean±standard deviation, multiple independent groups was used ANOVA, enumeration data and ranked data usingχ~2 test, with P<0.05 as statistically significant.Results: The three groups in gender, body mass index, smoking, drinking, high blood pressure, blood lipids, glycated hemoglobin, blood glucose, insulin, C-peptide, kidney function, medication, coronary angiography lesions, stents types, etc. connection was no statistical difference. The results of coronary angiography showed that the ratio of the patients with <TIMIⅢgrade in the three groups were statistically significant difference (48.57% vs 17.14% vs 20%,χ~2=10.360 P=0.006<0.05), where A, B group differences were statistical significance (48.57% vs 17.14%, P=0.010<0.017); A group, C group differences were statistically significant (48.57% vs 20%, P=0.014<0.017); B group, C group no significant difference between (17.14% vs 20%, P =0.759>0.05). The results of Holter showed that the incidence of arrhythmia of the three groups were significantly difference(22.86% vs 48.57% vs 51.54%,χ~2=8.810, P=0.012<0.05), A and B group differences were statistically significant (22.86% vs 48.57%,χ~2=6.341, P=0.012<0.05); A group, C group differences were statistically significant (22.86% vs 51.54%,χ~2 =7.529, P=0.006<0.017), B group, C group no statistically significant difference (48.57% vs 51.54%,χ~2=0.057, P=0.881>0.05). The arrhythmia scores were statistically significant differences between the three groups (10 vs 25 vs 23,χ~2=7.410, P=0.025<0.05), where A, B group the differences were statistically significant (10 vs 25,χ~2=6.991, P=0.008 <0.017), A group, C group differences were statistically significant (10 vs 23,χ~2=5.915, P=0.015<0.017), B group, C group were not statistically significant difference (25 vs 23,χ~2=0.195, P=0.659>0.017). ECT results showed that In the rest state, the ratio of abnormal myocardial perfusion segments in the three groups were statistically significant difference (32.90% vs 25.97% vs 26.15%, P=0.003<0.05); where A, B group were statistically significant difference (32.90% vs 25.97%, P=0.013<0.017); A group, C group were statistically significant difference (32.90% vs 26.15%, p P=0.001<0.017); B group, C group were not statistically significant difference (25.97% vs 26.15%, P= 0.929>0.05); The ischemic myocardial area score A group was significantly higher than B group and C group (380 vs 300, P=0.013<0.017 ), (380vs302, P =0.001<0.017); B group and C group were no significant difference (300 vs 302, P=0.929>0.017). ERNA showed that LVEF in the three groups were statistically significant difference (53%vs(56.51±4.23)% vs 60%,χ~2 =21.479, P=0.000<0.05), A group was significantly lower than B group [53% vs (56.51±4.23)%, P=0.001<0.017]; there were no significant difference between B group and C group [(56.51±4.23)% vs 60%, P=0.033>0.017], A group, C group differences were statistically significant (53% vs 60%,χ~2=4.545, P=0.000<0.017), illustrated the LVEF of A group was significantly lower than B group and C group.Conclusion: 1. The ischemic areas of myocardial perfusion imaging of the patients who had long histories of application of glibenclamide was higher than those of the insulin and diet groups, suggesting that glibenclamide would increase myocardial ischemic area in patients with acute myocardial infarction and type 2 diabetes mellitus, And it would decrease the LVEF severely.2. Glibenclamide had significant adverse effects on TIMI grade of the coronary flow in the patients with acute myocardial infarction and type 2 diabetes mellitus. 3. Glibenclamide increases the possibility of malignant arrhythmias in the patients with acute myocardial infarction and type 2 diabetes mellitus.更多还原