2型糖尿病并发脑梗死患者颈动脉粥样硬化与vWF、AT的关系
发布时间：2018-08-15 14:00
【摘要】：2型糖尿病是一种常见疾病,脑梗死是大血管并发症之一,是糖尿病患者致死、致残的主要原因之一。UKPDS和ADVANCE研究报告指出:2型糖尿病大血管病变发病率高,强化降糖治疗对于大血管病变没有显著疗效。提醒我们要重视对大血管并发症的预防,对2型糖尿病患者实施早期筛查和治疗以预防脑梗死的发生是十分必要的。目前认为2型糖尿病并发大血管病变的病理基础是动脉粥样硬化,血管内皮细胞受损,致血管内壁狭窄,容易促进局部血栓的形成。动脉粥样硬化尤其是向脑部供应血液的颈部血管发生动脉粥样硬化,造成的血管内径狭窄或斑块坠落是导致缺血性脑血管事件的主要原因。研究发现,2型糖尿病并发脑梗死患者通常会存在血管内皮细胞系统、凝血、抗凝及纤溶系统的异常变化。血管性血友病因子(vWF)是目前公认的血管内皮受损和功能紊乱的血浆标志物,与动脉血栓性疾病的发生及预后联系密切。多项临床研究均表明,急性脑梗死患者血浆vWF水平显著性升高,提示血浆vWF水平增高可能与缺血性脑卒中的病理状况相关。据相关文献报道,脑梗死尤其是在急性期,机体处于高凝状态,抗凝血酶(AT)被大量消耗,造成血管内凝血功能亢进,同时AT合成减少,提示AT参与脑梗死凝血功能障碍这一病理生理过程。现阶段,2型糖尿病并发脑梗死的发病原理仍尚未完全明确,因此,掌握2型糖尿病并发脑梗死的发病机制将是进行有针对性的治疗的关键。目的:本研究旨在观察2型糖尿病并发脑梗死患者颈动脉粥样硬化状况与血浆中vWF、AT的表达,分析其与2型糖尿病合并脑梗死病变过程的关联性,探讨糖尿病脑梗死的相关机制,从而为临床上防治2型糖尿病脑血管事件提供一定依据。方法:选取2015年12月到2016年5月间在承德市中心医院就诊的125例患者,将入选者分为三组:(1)2型糖尿病并发脑梗死组(DMCI组),n=44;(2)2型糖尿病组(DM组),n=51。(3)对照组(CN组),n=30:为同期在本院体检中心体检的健康人群。依据是否存在颈动脉粥样硬化斑块,进一步将各组分为有动脉斑块组(EAP组)、无动脉斑块组(NAP组);再依据斑块的不同性质,将EAP组分为稳定斑块组(SP组)和不稳定斑块组(USP组)。全部收录对象近一个月内未服用过促凝、抗凝及溶栓类药物。三组在年龄、性别等一般资料上具有均衡性。详细询问所有入选对象的病史,测量并记录身高、体重、血压、糖尿病病程、吸烟史,并计算体重指数(BMI)。取空腹静脉血,采取免疫比浊法测定血浆vWF水平;采取发色底物法测定血浆AT水平;应用全自动生化分析仪测定甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C);采取液相色谱法测定糖化血红蛋白(Hb A1c);采用彩色多普勒超声仪检测三组颈动脉斑块情况。采用SPSS19.0软件进行统计学分析,符合正态分布的计量资料用均数±标准差(?)表示,两组间比较采用t检验,三组间比较采用方差分析(两两比较采用LSD法),计数资料采用χ~2检验,P0.05为差异有统计学意义。结果:1三组间一般资料的比较(1)三组在年龄、BMI方面的差别无统计学意义,P=0.522、P=0.1(P0.05),三组在性别、吸烟史方面的差异无统计学意义,χ~2=3.56,P=0.169(P0.05)、χ~2=2.688,P=0.1261(P0.05);(2)DMCI组的DM病程长于DM组,差别有统计学意义,P=0.043(P0.05)。2三组间生化指标的比较三组在vWF、AT、Hb A1c、TC、HDL-C的差别有统计学意义(P0.05);三组在TG、LDL-C的差别不存在统计学意义(P0.05);组间比较:DMCI组的vWF、Hb A1c、TC均高于DM组和CN组(P0.05或P0.01),且DM组高于CN组(P0.05或P0.01);DMCI组的AT、HDL-C均低于DM组和CN组(P0.05或P0.01),且DM组低于CN组(P0.05)。3三组间超声指标的比较(1)三组颈动脉斑块检出率的比较三组在颈动脉斑块检出率之间的差别具有统计学意义(P0.01);组间比较:DMCI组与DM组的颈动脉斑块检出率均高于CN组(χ~2=27.81,P0.01、χ~2=4.67,P0.05);DMCI组的颈动脉斑块检出率高于DM组(χ~2=13.44,P0.01)。(2)三组不同性质颈动脉斑块检出率的比较三组在颈动脉不同性质斑块检出率方面的差别具有统计学意义(P0.01);组间比较:DMCI组的颈动脉不稳定性斑块检出率高于DM组、CN组,(χ~2=5.77,P0.05、χ~2=8.51,P0.01),差别有统计学意义;DM组的颈动脉不稳定性斑块检出率高于CN组,但是差别不存在统计学意义(χ~2=1.59,P0.05)。4 DMCI组患者各指标的相关性(1)vWF水平与DMCI各亚组颈动脉斑块性质的关系(?)DMCI组患者vWF水平显著高于DM组(P0.05)。DMCI组内不稳定斑块患者vWF水平显著高于稳定斑块、无斑块患者的vWF水平,差异有统计学意义(P=0.023,P0.05、P=0.016,P0.01);稳定斑块患者vWF水平高于无斑块患者,但差别不存在统计学意义(P=0.129,P0.05)。(2)AT水平与DMCI各亚组颈动脉斑块性质的关系(?)DMCI组患者AT水平显著低于DM组(P0.05)。DMCI组不稳定斑块患者AT水平低于稳定斑块、无斑块患者的AT水平,差异具有统计学意义(P=0.038,P0.05、P=0.02,P0.05);稳定斑块患者AT水平与无斑块患者AT水平之间的差异不具有统计学意义(P=0.103,P0.05)。结论:1 2型糖尿病并发脑梗死患者发生颈动脉粥样硬化斑块的病变率明显增高。2 2型糖尿病并发脑梗死患者的血浆vWF水平与颈动脉粥样硬化相关,斑块越不稳定vWF水平升高越显著。vWF在一定程度上可以反映颈动脉粥样硬化斑块的性质,可作为辅助临床诊疗和反映疾病进展的一项非损伤性指标。3 2型糖尿病并发脑梗死患者的血浆AT水平与颈动脉粥样硬化相关,斑块越不稳定AT水平降低越明显。AT在一定程度上可以反映颈动脉粥样硬化斑块的性质。4 2型糖尿病并发急性脑梗死患者血管内皮功能损伤越重,颈动脉粥样硬化斑块越不稳定,降低vWF水平、增高AT水平,对于防治2型糖尿病患者发生颈动脉粥样硬化和脑梗死具有重要意义。
[Abstract]:Type 2 diabetes mellitus is a common disease. Cerebral infarction is one of the complications of large vessels and one of the main causes of death and disability in diabetic patients. Early screening and treatment of type 2 diabetes mellitus is necessary to prevent cerebral infarction. Atherosclerosis, vascular endothelial cell damage, vascular wall stenosis, and local thrombosis are the pathological basis of type 2 diabetes with macroangiopathy. The main cause of ischemic cerebrovascular events is atherosclerosis of the cervical vessels supplying blood to the brain, resulting in narrow vessel diameters or falling plaques. Studies have found that patients with type 2 diabetes complicated by cerebral infarction usually have abnormal changes in the vascular endothelial cell system, coagulation, anticoagulation and fibrinolysis system. Etiological factors (vWF) are recognized as plasma markers of vascular endothelial damage and dysfunction, and are closely related to the occurrence and prognosis of arterial thrombotic diseases. Several clinical studies have shown that the plasma vWF levels in patients with acute cerebral infarction are significantly elevated, suggesting that the elevated plasma vWF levels may be related to the pathological status of ischemic stroke. Relevant literatures reported that cerebral infarction, especially in acute phase, is in hypercoagulable state, and antithrombin (AT) is consumed in large quantities, resulting in hypercoagulability in blood vessels, and AT synthesis is reduced, suggesting that AT participates in the pathophysiological process of coagulation dysfunction in cerebral infarction. Objective: To investigate the relationship between carotid atherosclerosis and the expression of vWF and AT in plasma of type 2 diabetes mellitus patients with cerebral infarction, and to explore the relationship between the expression of vWF and AT and the process of type 2 diabetes mellitus complicated with cerebral infarction. Methods: From December 2015 to May 2016, 125 patients in Chengde Central Hospital were divided into three groups: (1) type 2 diabetes complicated with cerebral infarction group (DMCI group), n = 44; (2) type 2 diabetes mellitus group (DM group), n = 51. (3) pairs The control group (CN group), n = 30: healthy people who were checked up in the physical examination center of our hospital at the same time. According to the existence of carotid atherosclerotic plaques, each group was further divided into arterial plaque group (EAP group), non-arterial plaque group (NAP group); and then according to the different nature of the plaque, EAP group was divided into stable plaque group (SP group) and unstable plaque group (USP group). The subjects did not take anticoagulant, anticoagulant and thrombolytic drugs in the past month. The three groups were balanced in age and sex. All the subjects were asked about their medical history, height, weight, blood pressure, duration of diabetes, smoking history, and body mass index (BMI). Fasting venous blood was taken and measured by immunoturbidimetric method. The levels of plasma vWF, AT, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glycosylated hemoglobin (Hb A1c) and color Doppler ultrasonography (CDU) were used to detect the three groups. Carotid plaque was analyzed by SPSS19.0 software. The normal distribution measurement data were expressed by mean (?) standard deviation. The comparison between the two groups was performed by t test. The comparison among the three groups was performed by analysis of variance (two comparisons were performed by LSD method). The counting data were analyzed by_~2 test. The difference was statistically significant (P 0.05). There was no significant difference in age and BMI among the three groups (P = 0.522, P = 0.1 (P 0.05). There was no significant difference in sex and smoking history among the three groups, _~2 = 3.56, P = 0.169 (P 0.05), _~2 = 2.688, P = 0.1261 (P 0.05); (2) The duration of DM in DMCI group was longer than that in DM group (P = 0.043) (P 0.05). There were significant differences in VWF, AT, Hb A1c, TC, HDL-C among the three groups (P 0.05); there was no significant difference in TG, LDL-C among the three groups (P 0.05); the comparison among the three groups: vWF, Hb A1c, TC in DMCI group were higher than those in DM group and CN group (P 0.05 or P 0.01), and the AT, HDL-C in DM group were lower than those in DM group and CN group (P 0.05 or P 0.01); the AT, HDL-C in DMCI group were lower than those in DM group and CN group (P 0.05 or P 0.01). The detection rate of carotid plaque in DMCI group and DM group was higher than that in CN group (_~2=27.81, P 0.01, _~2=4.67, P 0.05). The detection rate of carotid plaque in DMCI group was higher than that in DM group (_~2=13.44, P 0.01). (2) The detection rate of carotid plaque in three groups was statistically significant (P 0.01); the detection rate of carotid unstable plaque in DMCI group was higher than that in DM group, CN group (_~2=5.77, P 0.05, _~2=8.51, P 0.01). The detection rate of carotid artery unstable plaque in DM group was higher than that in CN group, but there was no significant difference (_~2=1.59, P 0.05). 4 The correlation between vWF level and carotid artery plaque properties in DMCI group was significant (1) The vWF level in DMCI group was significantly higher than that in DM group (P 0.05). The level of vWF in patients with stable plaque was significantly higher than that in patients without stable plaque (P = 0.023, P 0.05, P = 0.016, P 0.01); the level of vWF in patients with stable plaque was higher than that in patients without plaque, but the difference was not statistically significant (P = 0.129, P 0.05). (2) The relationship between AT level and the nature of carotid plaque in DMCI subgroups (?) The AT level of patients with unstable plaque was lower than that of patients without stable plaque (P = 0.038, P 0.05, P = 0.02, P 0.05). There was no significant difference between AT level of patients with stable plaque and that of patients without plaque (P = 0.103, P 0.05). The incidence of carotid atherosclerotic plaque in patients with diabetes mellitus complicated with cerebral infarction was significantly increased. The plasma vWF level in patients with type 2 diabetes complicated with cerebral infarction was associated with carotid atherosclerosis. The more unstable the plaque, the higher the vWF level was. The vWF could reflect the nature of carotid atherosclerotic plaque to some extent and could be used as an adjuvant. 3. The plasma AT level in type 2 diabetes mellitus patients with cerebral infarction is associated with carotid atherosclerosis, and the more unstable the plaque, the more obvious the decrease of AT level. AT can reflect the nature of carotid atherosclerotic plaque to a certain extent. 4. Type 2 diabetes mellitus patients with acute cerebral infarction The more serious vascular endothelial dysfunction, the more unstable carotid atherosclerotic plaque, the lower the level of vWF, the higher the level of AT, for the prevention and treatment of type 2 diabetes carotid atherosclerosis and cerebral infarction is of great significance.
【学位授予单位】：承德医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R743.33
本文编号：2184420
[Abstract]:Type 2 diabetes mellitus is a common disease. Cerebral infarction is one of the complications of large vessels and one of the main causes of death and disability in diabetic patients. Early screening and treatment of type 2 diabetes mellitus is necessary to prevent cerebral infarction. Atherosclerosis, vascular endothelial cell damage, vascular wall stenosis, and local thrombosis are the pathological basis of type 2 diabetes with macroangiopathy. The main cause of ischemic cerebrovascular events is atherosclerosis of the cervical vessels supplying blood to the brain, resulting in narrow vessel diameters or falling plaques. Studies have found that patients with type 2 diabetes complicated by cerebral infarction usually have abnormal changes in the vascular endothelial cell system, coagulation, anticoagulation and fibrinolysis system. Etiological factors (vWF) are recognized as plasma markers of vascular endothelial damage and dysfunction, and are closely related to the occurrence and prognosis of arterial thrombotic diseases. Several clinical studies have shown that the plasma vWF levels in patients with acute cerebral infarction are significantly elevated, suggesting that the elevated plasma vWF levels may be related to the pathological status of ischemic stroke. Relevant literatures reported that cerebral infarction, especially in acute phase, is in hypercoagulable state, and antithrombin (AT) is consumed in large quantities, resulting in hypercoagulability in blood vessels, and AT synthesis is reduced, suggesting that AT participates in the pathophysiological process of coagulation dysfunction in cerebral infarction. Objective: To investigate the relationship between carotid atherosclerosis and the expression of vWF and AT in plasma of type 2 diabetes mellitus patients with cerebral infarction, and to explore the relationship between the expression of vWF and AT and the process of type 2 diabetes mellitus complicated with cerebral infarction. Methods: From December 2015 to May 2016, 125 patients in Chengde Central Hospital were divided into three groups: (1) type 2 diabetes complicated with cerebral infarction group (DMCI group), n = 44; (2) type 2 diabetes mellitus group (DM group), n = 51. (3) pairs The control group (CN group), n = 30: healthy people who were checked up in the physical examination center of our hospital at the same time. According to the existence of carotid atherosclerotic plaques, each group was further divided into arterial plaque group (EAP group), non-arterial plaque group (NAP group); and then according to the different nature of the plaque, EAP group was divided into stable plaque group (SP group) and unstable plaque group (USP group). The subjects did not take anticoagulant, anticoagulant and thrombolytic drugs in the past month. The three groups were balanced in age and sex. All the subjects were asked about their medical history, height, weight, blood pressure, duration of diabetes, smoking history, and body mass index (BMI). Fasting venous blood was taken and measured by immunoturbidimetric method. The levels of plasma vWF, AT, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glycosylated hemoglobin (Hb A1c) and color Doppler ultrasonography (CDU) were used to detect the three groups. Carotid plaque was analyzed by SPSS19.0 software. The normal distribution measurement data were expressed by mean (?) standard deviation. The comparison between the two groups was performed by t test. The comparison among the three groups was performed by analysis of variance (two comparisons were performed by LSD method). The counting data were analyzed by_~2 test. The difference was statistically significant (P 0.05). There was no significant difference in age and BMI among the three groups (P = 0.522, P = 0.1 (P 0.05). There was no significant difference in sex and smoking history among the three groups, _~2 = 3.56, P = 0.169 (P 0.05), _~2 = 2.688, P = 0.1261 (P 0.05); (2) The duration of DM in DMCI group was longer than that in DM group (P = 0.043) (P 0.05). There were significant differences in VWF, AT, Hb A1c, TC, HDL-C among the three groups (P 0.05); there was no significant difference in TG, LDL-C among the three groups (P 0.05); the comparison among the three groups: vWF, Hb A1c, TC in DMCI group were higher than those in DM group and CN group (P 0.05 or P 0.01), and the AT, HDL-C in DM group were lower than those in DM group and CN group (P 0.05 or P 0.01); the AT, HDL-C in DMCI group were lower than those in DM group and CN group (P 0.05 or P 0.01). The detection rate of carotid plaque in DMCI group and DM group was higher than that in CN group (_~2=27.81, P 0.01, _~2=4.67, P 0.05). The detection rate of carotid plaque in DMCI group was higher than that in DM group (_~2=13.44, P 0.01). (2) The detection rate of carotid plaque in three groups was statistically significant (P 0.01); the detection rate of carotid unstable plaque in DMCI group was higher than that in DM group, CN group (_~2=5.77, P 0.05, _~2=8.51, P 0.01). The detection rate of carotid artery unstable plaque in DM group was higher than that in CN group, but there was no significant difference (_~2=1.59, P 0.05). 4 The correlation between vWF level and carotid artery plaque properties in DMCI group was significant (1) The vWF level in DMCI group was significantly higher than that in DM group (P 0.05). The level of vWF in patients with stable plaque was significantly higher than that in patients without stable plaque (P = 0.023, P 0.05, P = 0.016, P 0.01); the level of vWF in patients with stable plaque was higher than that in patients without plaque, but the difference was not statistically significant (P = 0.129, P 0.05). (2) The relationship between AT level and the nature of carotid plaque in DMCI subgroups (?) The AT level of patients with unstable plaque was lower than that of patients without stable plaque (P = 0.038, P 0.05, P = 0.02, P 0.05). There was no significant difference between AT level of patients with stable plaque and that of patients without plaque (P = 0.103, P 0.05). The incidence of carotid atherosclerotic plaque in patients with diabetes mellitus complicated with cerebral infarction was significantly increased. The plasma vWF level in patients with type 2 diabetes complicated with cerebral infarction was associated with carotid atherosclerosis. The more unstable the plaque, the higher the vWF level was. The vWF could reflect the nature of carotid atherosclerotic plaque to some extent and could be used as an adjuvant. 3. The plasma AT level in type 2 diabetes mellitus patients with cerebral infarction is associated with carotid atherosclerosis, and the more unstable the plaque, the more obvious the decrease of AT level. AT can reflect the nature of carotid atherosclerotic plaque to a certain extent. 4. Type 2 diabetes mellitus patients with acute cerebral infarction The more serious vascular endothelial dysfunction, the more unstable carotid atherosclerotic plaque, the lower the level of vWF, the higher the level of AT, for the prevention and treatment of type 2 diabetes carotid atherosclerosis and cerebral infarction is of great significance.
【学位授予单位】：承德医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R743.33
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