论文标题:肥胖T2DM脂肪组织PAI-1基因表达与胰岛素抵抗及血管病变的相关性研究
Part one Correlations between 4G/5G Polymorphism in PAI-1 Gene Promotor Region and Type 2 Diabetes Vascular Complications
论文作者 唐宽晓
论文导师 陈丽,论文学位 博士,论文专业 内科学
论文单位 山东大学,点击次数 1103,论文页数 131页File Size6687k
2004-05-01论文网 http://www.lw23.com/lunwen_79657/ PAI-1基因;胰岛素抵抗;肥胖;体成分;2型糖尿病;糖尿病肾病;糖尿病视网膜病变;冠心病
PAI-1 gene; obesity; body composition; insulin resistance; type 2 diabetes; diabetic nephropathy; diabetic retinopathy; coronary heart disease
研究目的: 1.探讨中国北方汉族肥胖2型糖尿病(DM)患者PAI-1基因型、等位基因分布特点及其与体成分、胰岛素敏感性、血浆纤溶功能的相互关系。 2.从血液纤溶机制角度,探讨PAI-1基因多态性与肥胖2型糖尿病(DM)患者血管并发症的相关性。 对象与方法: 1.研究对象:选取山东地区汉族人、无血缘关系的受试者187例。(1)T2DM组:147例,男76例,女71例,年龄均>50岁,平均年龄59.98±10.52岁,平均体重指数(BMI)为(25.58±3.90)kg/m~2。按照BMI分为:①肥胖及超重(BMI≥3kg/m~2)组(OBDM组)105例,其中男57例,女48例,平均BMI为(26.99±3.28)kg/m~2。②正常体重(23kg/m2>BMI>18.5kg/m~2)T2DM组(NWDM组)42例,其中男19例,女23例,平均BMI为(20.89±1.37)kg/m~2。按照有无血管并发症又分为:①糖尿病无并发症组(DMNC组):49例,男22例,女27例。其中,正常体重者(NWDMNC组)16例,超重及肥胖者(OBDMNC组)33例。②糖尿病肾病组(DN组):24小时尿液微量白蛋白排泄率(UAER)>20μg/min诊断DN,20～200μg/min为微量白蛋白尿,>200μg/min为大量白蛋白尿。共59例,男28例,女31例,平均年龄(59.20±11.08)岁,平均BMI(26.02±4.25)kg/m~2,其中DNⅢ期44例,Ⅳ期12例,Ⅴ期3例。按BMI又分为:正常体重DN组(NWDN)19例及超重肥胖DN组(OBDN)40例;③糖尿病视网膜病变(DR)组:69例,背景型60例,增值型9例,男38例,女31例,平均年龄(61.87±9.75)岁,平均BMI(24.46±3.70)kg/m~2。
Objective:The aim of this study is to disclose the PAI-1 genotype, alleles distribution features in obese type 2 diabetic patients of northern China Han nationality and their relationships between the body composition, insulin sensitivity and plasma fibrinolysis function, and from view of the blood fibrinolysis mechanism, we want to explore the relationships between PAI-1 gene polymorphism and vascular complications in obese type 2 diabetic patients.Subjects and methods:1.Subjects: 187 patients with no consanguinity were selected from Han nationality in Shandong district.(1)T2DM group: 147 patients, 76 men 71 women . All the patients were over 50 years old old. The mean age was (59.98 ±10.52) years old .The mean body mass index (BMI) was (25.58±3.90)kg/m~2.Based on the BMI, the patients were divided into two groups: ①Obese and overweight(BMI ≥ 23kg/m~2) group (OBDM): 105 patients, there are 57 male and 48 female patients among them, the mean BMI was (26.99 ± 3.28)kg/m~2. ② Normal weight(23kg/m~2>BMI≥18.5kg/m~2)T2DM (NWDM) group:42 patients, there are 19 male and 23 female patients among them, the mean BMI was(20.89 ± 1.37)kg/m~2.Based on the vascular complication conditions, the patients were divided into 4 groups:①DM with no complications group(DMNC group):49 patients, 22 men, 27 women. There were 16 normal weight (NWDMNC group) and 33 overweight or obese (OBDMNC group) patients among them.②Diabeticnephropathy group (DN group): DN was defined as 24 hours urine albumin excretion rate(UAER)>20mg/min, UAER between 20 and 200mg /min was diagnosed as micro-albumin urine, UAER over 200mg/min was diagnosed as macro- albumin urine.59 patients in all, there were 28 men and 31 women in them, the mean age was(59.20 ± 11.08)years old ,the mean BMI was(26.02 ± 4.25)kg/m2. Among them, 44 were in DNIII phase ,12 in IV phase and 3 in V phase .Based on the BMI, the patients were divided into two groups: normal weight DN group(NWDN),it involved 19 patients ; overweight and obese DN group(OBDN), it involved 40 patients;(3)Diabetic retinopathy(DR)group:69 patients in all, 60 patients were of background type, 9 patients were of proliferative type. Among them , 38 men,31 women, the mean age was (61.87±9.75)years old, mean BMI was (24.46±3.70)kg/m2.Based on the BMI the patients were divided into two groups: normal weight DR group(NWDR) involved 27 patients, and overweight and obese DR group(OBDR) involved 42 patients; ?T2DM complicated with coronary heart disease(DM-CHD)group: involved 75 patients,35 men ,40 women, the mean age was(61.88 ± 9.65)years old ,the mean BMI was (25.89 ± 4.19)kg/m2.Based on BMI the patients were divided into two groups: normal weight DMCHD (NWDMCHD) group involved 13 patients, and overweight and obese DMCHD (OBDMCHD) group involved 62 patients. (2)Normal control(NC) group:38 subjects, 17 men ,21 women, the mean age was (61.55±7.23)years old, the mean BMI was (23.78±2.27)kg/m2. Based on BMI the subjects were divided into normal weight control(NWNC) group involved 17 subjects; obese control(OBNC group) involved 21 subjects.2.Research content and methods: (l)History collection; (2) Anthropometric measurements: including height > weighu waist circumference> hip circumference and blood pressure. BMI and WHR were calculated from above measurements; (3) Body composition analysis: the whole body and local composition were measured by bioelectrical impedance assay (BIA) and dual energy x-ray absorptiometry (DEXA); (4) Samples collection: Over night fasting venous blood was collected .After centrifugation, we extracted the plasma or serum for measurement of:? Metabolic variables: glucose-, blood lipid% HbA^ insulin. HOMA-IR.% HOMA-IS and ISI were calculated respectively; ?Plasma fibrinolysis system variables: the activity of tissue- plasminogen activator (t-PA) and concentrations of plasminogen activator inhibitor l(PAI-l), plasmin-antiplasmin complex (PAP) and D-dimer (D-D) were determined. (5) 24 hours urine albumin excretion rate (UAER): urine sample of 24 hours were used for measur
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