【作者】 洪兵；

【导师】 刘红； 夏宁； 冼苏； 罗佐杰；

【作者基本信息】 广西医科大学 ， 内分泌代谢学， 2003， 硕士

【摘要】 【目的】研究2型糖尿病患者脂联素（Adiponectin）与脂质代谢异常及其与年龄、性别、体重指数(Body-mass index ，BMI)、腰围、胰岛素敏感性和纤溶酶原激活物抑制因子-1（Plasminogen activator inhibitor type 1，PAI-1）等相关因素的关系，阐明这些因素在2型糖尿病心血管病变发生发展中的作用及机制，并探讨脂质干预对其心血管病变的影响。【方法】采用放射免疫分析法（Radioimmunoassay ，RIA）和酶联免疫吸附法（Enzyme-linked immunoadsordent assay ，ELISA）分别测定2型糖尿病无心血管病变者（DM1组，25例），2型糖尿病伴心血管病变者（DM2组，36例）及正常对照组（NC组，30例）的空腹血清脂联素与血浆PAI-1水平。同时测定BMI，腰围，血压，空腹血糖（Fasting Blood Glucose ，FBG），空腹血胰岛素（Fasting Blood Insulin，FINS），C肽，糖化血红蛋白（HbA1C），血脂及尿微量白蛋白（Urinary Albumin Excretion ,UAE）等相关指标。在降糖、降压治疗基础上，两糖尿病组采用脂质干预治疗（低脂饮食加用调脂药物），12周后按美国胆固醇教育计划成人治疗组第三次指南（NCEP-ATPⅢ）标准，根据复查血脂水平分血脂控制满意组（A组，血脂各项指标均达理想水平；TC≤5.2 mmol/L， TG≤1.7 mmol/L， LDL-C≤2.6 mmol/L， HDL-C≥1.2 mmol/L）和血脂控制较差组（B组，至少有一血脂指标未达到理想水平）。【结果】 1. 糖尿病两组血清脂联素和ISI均低于正常对照组（分别为：6.89±2.52μg/ml 、5.24±1.49μg/ml 、12.30±4.71μg/ml, P<0.001；-4.08±0.90、-4.18±0.77、-3.44±0.59，P< 0.001） ；DM2组脂联素显著低于DM1组（P<0.05）。而PAI-1、TC、TG、TG比值和Homa-IR：糖尿病两组高于正常对照组（P< 0.01）；DM2组TG、TG比率显著高于DM1组（分别为：2.23±1.02 mmol/L vs1.61±0.81 mmol/L，2.30±1.29 vs 1.53±0.75，均P<0.05），DM2组血浆PAI-1、TC和Homa-IR高于DM1组的水平，但差异无统计学意义（P＞0.05）。2. 脂联素受性别、BMI影响：三组女性血清脂联素水平均高于同组男性(均P<0.01)；在糖尿病患者中超重肥胖组（BMI≥25kg/m2）血清<WP=6>脂联素水平明显低于同组非肥胖者（BMI<25kg/m2），(均P<0.05)。血浆PAI-1水平在不同性别和肥胖因素下差异无显著性（P＞0.05）。3. 在所有观察对象中，经调整性别、年龄和BMI等混杂因素后，偏相关分析显示：血清脂联素分别与腰围、臀围、腰臀比、收缩压、舒张压、空腹血糖、Homa-IR、TG、TG比率以及血浆PAI-1呈负相关,与ISI呈正相关。在此基础上，分别以脂联素为因变量，以性别、BMI以及上述相关因素等为自变量，进行多元逐步回归分析。结果显示： 性别、TG比率、FBG、腰围进入回归方程，是影响脂联素水平的独立相关因素。4. Logistic回归结果显示：低脂联素血症和高甘油三酯血症是糖尿病心血管病变的独立危险因子。5.不同血脂控制组治疗后脂联素分别为：14.81±4.44μg/ml vs 10.68±4.57μg/ml，有显著性差异（P<0.001）。【结论】2型糖尿病存在脂质代谢异常、低脂联素血症和高PAI-1血症，在糖尿病心血管病变时更为显著；低脂联素血症是2型糖尿病心血管病变的危险因素和预测因子之一。脂联素水平受性别和肥胖因素影响；空腹血糖、腰围和甘油三酯比率是影响脂联素的重要因素。脂质代谢异常的改善可导致血清脂联素水平升高，从而可以延缓和阻止糖尿病动脉粥样硬化性血管病变的发展。更多还原

【Abstract】 【Objective】　To investigate the relationships between serum adiponectin levels, dyslipidemia , plasm plasminogen activator inhibitor-1(PAI-1) and body mass index (BMI), age, gender, insulin sensibitity and some related factors in 61 patients with type 2 diabetes accompanied with or without cardiovascular disease, elucidate the role and mechanisms of these factors in development of type 2 diabetic cardiovascular diseases and discuss the effect of lipid intervention on them.【Methods】 By using radioimmunoassay (RIA) and enzyme linked immunosorbent assay(ELISA) methods,the fasting levels of serum adiponectin and plasm PAI-1 we remeasured in 30 healthy subjects, 25 patients with type 2 diabetes accompanied without cardiovascular disease( DM1) and 36 patients with type 2 diabetes accompanied with ischemic heart disease( DM2). BMI, waist circumference,blood pressure,the fasting blood glucose (FBG), fasting serum insulin(FINS),C peptide(FCP) ,total cholesterol(TC), triglyceride(TG) , LDL-C, HDL-C, HbA1c and urine albumin excretory rate (UAE) were reassayed simultaneously. On the basis of reducing blood glucose and blood pressure positively ,all patients were taken low-lipid and diabetic diet and administrated with some medicines which can normolize blood lipid level,who act as lipid intervention therapy. Serum glucose and lipid were measured regularly,and after 12 weeks’treatment serum lipid,serum adiponectin and plasm PAI-1 were remeasured.With respect to the reference standard maken by ATPIII of NCEP, all patients were divided into two groups according to the levels of remeasured blood lipids after 12 weeks treatments.Satisfactory groups(A group):The concentrations of serum TC,TG,LDL-C and HDL-C were all controlled well(TC≤5.2mmol/L,TG≤1.7 mmol/L、LDL-C≤2.6 mmol/L,HDL-C≥1.2 mmol/L).Unsatisfactory group(B group):At least one lipid marker were not in a satisfactory coverage. 【Results】 1.There was obvious difference between the levels of adiponectin, TC,TG, TG/HDL-C, Homa-IR,ISI and plasm PAI-1 in patients with type 2 diabetes mellitus and the normal control group. The serum adiponectin levels and ISI were significantly lower in type 2 diabetes mellitus group than in normal control group(6.89±2.52μg/ml,5.24±1.49μg/ml vs 12.31±4.71μg/ml, P< 0.001; -4.08±0.90, -4.18±0.77 vs -3.44±0.59, P< 0.001, respectively).Besides,the serum adiponectin levels were significantly lower in DM2 group than in DM1 group (P< 0.05). The levels of PAI-1, TC,TG,TG/HDL-C and Homa-IR were significantly higher in type 2 diabetes mellitus group than in normal control group ( P< 0.01), the levels of TG and TG/HDL-C were significantly higher in DM2 group than in DM1 group (2.23±1.02 mmol/L vs1.61±0.81 mmol/L, P< 0.05;2.30±1.29 vs 1.53±0.75,P< 0.05,<WP=8>respectively). The levels of PAI-1,TC and Homa-IR were higher in DM2 group than in DM1 group but not significantly. 2.The serum adiponectin levels were significantly higher in women of every group than in men of the same groups ( 16.73±3.28μg/ml vs10.96±4.26μg/ml,t = -3.086,P< 0.01;9.05±1.32μg/ml vs5.87±2.31μg/ml ,t = -3.351, P< 0.01;6.38±1.36μg/ml vs 4.92±1.38μg/ml,t = -2.572, P< 0.05, respectively) .The serum adiponectin levels were significantly lower in diabetic patients with overweight and obesity(BMI≥25kg/m2)than those non-obesity (BMI< 25kg/m2) (4.30±1.25μg/ml vs 8.11±1.98μg/ml,t = 5.308,P< 0.001;4.68±1.66μg/ml vs 5.65±1.25μg/ml,t =2.974,P< 0.05, respectively ) .There was no significant difference in the levels of plasm PAI-1 between different sex groups,same results were found in obesity and non-obesity groups (p> 0.05). 3.The serum adiponectin levels were negatively correlates with waist circumference ,hip circumference, WHR,systolic pressure, diastolic pressure, fasting glucose,Homa-IR, TG,TG/HDL-C and plasm PAI-1, and positively correlated with ISI(P< 0.05) after adjusting such confounding factors as sex,age,BMI,etc. The results of multi-factor stepwise regression analysis indicate there were an indepandent correlation between serum adi更多还原