成人1型糖尿病免疫学诊断研究

发布时间：2018-03-11 00:18

本文选题：1型糖尿病　切入点：成人　出处：《南京医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：第一部分成人1型糖尿病胰岛自身抗体与胰岛功能异质性分析目的:检测并分析成人1型糖尿病患者胰岛自身抗体的阳性率,探索其临床异质性,并分析影响成人1型糖尿病胰岛功能的因素。方法:分别采用放射免疫沉淀法和酶联免疫吸附测定法对741例18岁以上1型糖尿病患者进行谷氨酸脱羧酶抗体(Glutamic Acid Decarboxyase Antibody,GADA)、蛋白酪氨酸磷酸酶抗体(Protein Tyrosine Phosphatase-2 Antibody,IA-2A)、锌转运体8自身抗体(Zinc Transporter 8 Antibody,ZnT8A)、胰岛素自身抗体(IAA)及胰岛细胞抗体(Islet Cell Antibody,ICA)的检测,同时收集人口学基本信息、生化指标、口服糖耐量试验结果、人类白细胞抗原(Human Leukocyte Antigen,HLA)基因、治疗方式等数据。结果:成人1型糖尿病患者三种胰岛自身抗体的阳性率分别为GADA51.4%、ZnT8A38.8%、IA-2A29.2%,至少一个抗体阳性的阳性率为75.3%。经典1型糖尿病患者起病急骤,56.2%的患者可出现酮症酸中毒,至少两个抗体阳性患者起病年龄最小(31.1±12.4岁),BMI最低(20.5±3.6kg/m^2),胰岛功能最差(FCP155.6±145.8pmol/L)。将病程按照1年、5年、10年分成4组后发现,随着病程延长,至少一个抗体阳性率逐渐下降分别为79.7%、70.2%、70.9%、58.5%(P0.05),通过回归分析后发现,病程、BMI、GADA是导致胰岛功能衰竭的主要危险因素。此外,还发现抗体阳性患者携带A*2402-DRB1*0901、A*2402-DRB1*0301、A*1101-DRB1*0301、A*3303-DRB1*0301及A*1101-DRB1*0901的比例更高。结论:1型糖尿病患者胰岛自身抗体与胰岛功能均存在明显的异质性,需要结合临床指标及免疫标志物联合诊断。第二部分成人1型糖尿病免疫诊断模型建立与分析目的:建立中国人群成人1型糖尿病免疫诊断模型,提高诊断率。方法:运用Logistic逐步回归分析,在建模组(共计579人,包括373名1型糖尿病和206名2型糖尿病)和验证组(共计556人,包括368名1型糖尿病和188名2型糖尿病)人群中建立风险评估模型。所有患者均进行临床相关生化指标、胰岛自身抗体检测以及口服糖耐量试验。模型建立后使用ROC工作曲线进行效能评估。结果:根据发病年龄、身高、体重指数、糖化血红蛋白、胰岛素曲线下面积、胰岛素/血糖曲线下面积比值以及胰岛素敏感性指标,我们建立了两个模型,两种模型ROC工作曲线下面积差异无统计学差异。最终我们选择的模型ROC曲线下面积在建模组和验证组人群分别为0.811(0.763-0.859)和0.770(0.717-0.822)。当切点值设定为5.7392时,模型预测的灵敏度和特异度分别为75.2%和78.8%。结论:我们建立了一种使用常规临床指标对成人1型糖尿病进行免疫诊断的模型,在缺乏胰岛自身抗体检测结果时,这将能够有效地对成人1型糖尿病和2型糖尿病进行鉴别诊断。
[Abstract]:Part one: analysis of islet autoantibodies and islet function heterogeneity in adults with type 1 diabetes objective: to detect and analyze the positive rate of islet autoantibodies in adults with type 1 diabetes mellitus and to explore the clinical heterogeneity of islet autoantibodies. The factors influencing the islet function of adult type 1 diabetes mellitus were analyzed. Methods: the glutamate decarboxylase antibody (Glutamic Acid) was measured by radioimmunoprecipitation and enzyme-linked immunosorbent assay (Elisa) in 741 patients with type 1 diabetes over 18 years of age. Detection of Decarboxyase antibody-GADAA, protein Tyrosine Phosphatase-2 antibody antibody IA-2An, zinc transporter 8 autoantibody zinc Transporter 8 antibody, insulin autoantibody (IIA) and islet Cell Antibody (IIA). At the same time, the basic demographic information, biochemical indexes, oral glucose tolerance test (OGTT), human leukocyte antigen (Leukocyte antigenHLA) gene were collected. Results: the positive rates of three islet autoantibodies in adult patients with type 1 diabetes were GADA51.4, ZnT8A38.8and IA-2A29.2.The positive rate of at least one antibody was 75.3.The incidence of ketoacidosis was 56.2% in patients with classic type 1 diabetes. At least two patients with positive antibodies had the lowest onset age of 31.1 卤12.4 years of age and the lowest BMI of 20.5 卤3.6 kg / m ^ 2, and the worst function of islets was 155.6 卤145.8 pmol / L 路L ~ (-1). The course of disease was divided into 4 groups according to year, five, and ten years, and it was found that, as the course of disease was prolonged, The positive rate of at least one antibody gradually decreased by 79.70.2and 70.92 and 58.5and 58.5P0.05. by regression analysis, it was found that the course of disease and BMI-GADA were the main risk factors of islet failure. It was also found that the proportion of A1101-DRB1-0301 and A1101-DRB1-0301 and A1101-DRB1-0901 + positive patients were higher than that of patients with type 1 diabetes mellitus. Conclusion there is significant heterogeneity between islet autoantibodies and islet function in patients with type 1 diabetes mellitus. The second part is the establishment and analysis of the immune diagnosis model of adult type 1 diabetes mellitus objective: to establish the immune diagnosis model of Chinese adults with type 1 diabetes mellitus. Methods: using Logistic stepwise regression analysis, a total of 579 subjects (including 373 type 1 diabetes and 206 type 2 diabetes) and validation group (556 cases) were established. Risk assessment models were established in 368 patients with type 1 diabetes and 188 patients with type 2 diabetes. Islet autoantibody test and oral glucose tolerance test. ROC working curve was used to evaluate the effectiveness of the model. Results: according to age of onset, height, body mass index, glycosylated hemoglobin, area under insulin curve, We have established two models, the area ratio under the insulin / blood glucose curve and the insulin sensitivity index. There was no significant difference in the area under the working curve of ROC between the two models. In the end, the area under the ROC curve of the two models was 0.8110.763-0.859 in the model group and 0.7700.7717-0.822 in the validation group, respectively. When the tangent point was set to 5.7392, The predictive sensitivity and specificity of the model were 75.2% and 78.8 respectively. Conclusion: we have established a model for immunological diagnosis of adult type 1 diabetes mellitus using routine clinical indicators. This will enable effective differential diagnosis of type 1 diabetes and type 2 diabetes in adults.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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