發(fā)布時間：2018-03-11 00:18

  本文選題：1型糖尿病　切入點：成人　出處：《南京醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：第一部分成人1型糖尿病胰島自身抗體與胰島功能異質(zhì)性分析目的:檢測并分析成人1型糖尿病患者胰島自身抗體的陽性率,探索其臨床異質(zhì)性,并分析影響成人1型糖尿病胰島功能的因素。方法:分別采用放射免疫沉淀法和酶聯(lián)免疫吸附測定法對741例18歲以上1型糖尿病患者進行谷氨酸脫羧酶抗體(Glutamic Acid Decarboxyase Antibody,GADA)、蛋白酪氨酸磷酸酶抗體(Protein Tyrosine Phosphatase-2 Antibody,IA-2A)、鋅轉(zhuǎn)運體8自身抗體(Zinc Transporter 8 Antibody,ZnT8A)、胰島素自身抗體(IAA)及胰島細胞抗體(Islet Cell Antibody,ICA)的檢測,同時收集人口學(xué)基本信息、生化指標、口服糖耐量試驗結(jié)果、人類白細胞抗原(Human Leukocyte Antigen,HLA)基因、治療方式等數(shù)據(jù)。結(jié)果:成人1型糖尿病患者三種胰島自身抗體的陽性率分別為GADA51.4%、ZnT8A38.8%、IA-2A29.2%,至少一個抗體陽性的陽性率為75.3%。經(jīng)典1型糖尿病患者起病急驟,56.2%的患者可出現(xiàn)酮癥酸中毒,至少兩個抗體陽性患者起病年齡最小(31.1±12.4歲),BMI最低(20.5±3.6kg/m^2),胰島功能最差(FCP155.6±145.8pmol/L)。將病程按照1年、5年、10年分成4組后發(fā)現(xiàn),隨著病程延長,至少一個抗體陽性率逐漸下降分別為79.7%、70.2%、70.9%、58.5%(P0.05),通過回歸分析后發(fā)現(xiàn),病程、BMI、GADA是導(dǎo)致胰島功能衰竭的主要危險因素。此外,還發(fā)現(xiàn)抗體陽性患者攜帶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。結(jié)論:1型糖尿病患者胰島自身抗體與胰島功能均存在明顯的異質(zhì)性,需要結(jié)合臨床指標及免疫標志物聯(lián)合診斷。第二部分成人1型糖尿病免疫診斷模型建立與分析目的:建立中國人群成人1型糖尿病免疫診斷模型,提高診斷率。方法:運用Logistic逐步回歸分析,在建模組(共計579人,包括373名1型糖尿病和206名2型糖尿病)和驗證組(共計556人,包括368名1型糖尿病和188名2型糖尿病)人群中建立風(fēng)險評估模型。所有患者均進行臨床相關(guān)生化指標、胰島自身抗體檢測以及口服糖耐量試驗。模型建立后使用ROC工作曲線進行效能評估。結(jié)果:根據(jù)發(fā)病年齡、身高、體重指數(shù)、糖化血紅蛋白、胰島素曲線下面積、胰島素/血糖曲線下面積比值以及胰島素敏感性指標,我們建立了兩個模型,兩種模型ROC工作曲線下面積差異無統(tǒng)計學(xué)差異。最終我們選擇的模型ROC曲線下面積在建模組和驗證組人群分別為0.811(0.763-0.859)和0.770(0.717-0.822)。當(dāng)切點值設(shè)定為5.7392時,模型預(yù)測的靈敏度和特異度分別為75.2%和78.8%。結(jié)論:我們建立了一種使用常規(guī)臨床指標對成人1型糖尿病進行免疫診斷的模型,在缺乏胰島自身抗體檢測結(jié)果時,這將能夠有效地對成人1型糖尿病和2型糖尿病進行鑒別診斷。
[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 鹵12.4 years of age and the lowest BMI of 20.5 鹵3.6 kg / m ^ 2, and the worst function of islets was 155.6 鹵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.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.1

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本文編號：1595739