胰岛自身抗体与1型糖尿病

1617例糖尿病患者中自身抗体阳性率29．7％。单一抗体的阳性率明显低于3种抗体联合检测。多种胰岛自身抗体联合检测可提高1型糖尿病早期诊断的敏感性。谷氨酸脱羧酶抗体为成年糖尿病患者预示胰岛素依赖的较好的筛查试验，与酪氨酸蛋白磷酸酶抗体联合检测可达近100％的预报价值；而青少年糖尿病患者则还需检测胰岛细胞抗体。     

胰岛自身抗体与1型糖尿病

1型糖尿病是一种针对胰岛β细胞的自身免疫性疾病,患者体内有多种胰岛自身抗体存在,主要包括胰岛细胞抗体、胰岛素自身抗体、谷氨酸脱羧酶抗体,酪氨酸磷酸酶抗体等。随着这些抗体本质渐被揭示,检测方法趋于自动化,衡量标准趋于国际化,它们不仅被用于1型糖尿病的诊断和筛查,而且在对本病病因、发病机制和防治的研究中都起到了很大作用。     

锌转运体8及其自身抗体

锌是胰岛素储存和分泌机制中的一个重要组分,β细胞需要有效且特异的转运体来累积足够量的锌.锌转运体8(ZnT8)是新近发现的一种1型糖尿病自身抗原,具有高度β细胞特异性,通过影响锌离子浓度而在胰岛素合成和分泌中发挥重要作用.ZnT8自身抗体对自身免疫性糖尿病(尤其对其他自身抗体阴性者)有着重要的诊断与预测价值.ZnT8基因(SLC30A8基因)多态性影响ZnT8自身抗体的特异性.     

胰岛自身抗体与1型糖尿病

1型糖尿病是一种针对胰岛 β细胞的自身免疫性疾病 ,患者体内有多种胰岛自身抗体存在 ,主要包括胰岛细胞抗体、胰岛素自身抗体、谷氨酸脱羧酶抗体、酪氨酸磷酸酶抗体等。随着这些抗体本质渐被揭示 ,检测方法趋于自动化 ,衡量标准趋于国际化 ,它们不仅被用于 1型糖尿病的诊断和筛查 ,而且在对本病病因、发病机制和防治的研究中都起到了很大作用。     

胰岛自身抗体在诊断1型糖尿病中的价值

用受试者工作特性曲线和似然比的方法评价谷氨酸脱羧酶抗体 (GAD65 Ab)和胰岛细胞抗体 (ICA)对诊断 1型糖尿病的价值。GAD65 Ab优于ICA ;GAD65 Ab、ICA平行试验提高阳性检出率 ,GAD65 Ab、ICA的区间似然比 ,能反映 1型糖尿病患病概率的增减     

1型糖尿病一级亲属胰岛自身抗体与HLA-DQ基因型的关系

目的探讨1型糖尿病一级亲属谷氨酸脱羧酶抗体（GADA）、蛋白酪氨酸磷酸酶抗体（IA-2A）、胰岛素自身抗体（IAA）与HLA—DQ基因型之间的关系。方法横断面、病例对照研究。采用放射配体法检测351例糖耐量正常的1型糖尿病一级亲属与376名正常对照者GADA、IA-2A与IAA。其中156例自身免疫1型糖尿病一级亲属与278名正常对照采用PCR-直接测序法明确HLA-DQ基因型。结果（1）与正常对照比较，1型糖尿病一级亲属DQA1＊03、DQB1＊0303、＊0401等位基因与DQA1＊03-DQBl＊0303、DQA1＊05-DQB1＊0201、DQA1＊03-DQB1＊0401单体型频率增高（均P〈0．05或P〈0．01），而DQA1＊0601、＊0201和DQB1＊0301、＊0602等位基因与DQA1＊0102-DQB1＊0602单体型频率减少（均P〈0．05或P〈0．01）。（2）与1型糖尿病患者比较，1型糖尿病一级亲属DQA1＊03等位基因频率减少（45．8％vs54．5％，P〈0．05）。（3）携带DQA1＊03-DQB1＊0303单体型者，GADA、IA-2A与IAA任一自身抗体阳性率高于不携带此单体型者（23．0％们8．6％，P〈0．05）。结论携带DQA1＊03-DQB1＊0303单体型的一级亲属，GADA、IA-2A与IAA任一自身抗体检出率最高。     

胰岛B细胞特异性锌转运蛋白与1型糖尿病

1型糖尿病（T1DM）是胰岛呈进行性破坏的自身免疫性疾病,以表达于胰岛B细胞的分子靶点作为抗原参与自身免疫反应为特征。其中阳离子外流锌转运蛋白8（ZnT8,SLC30A8）是人类T1DM的主要自身抗原之一,T1DM患者中SLC30A8基因位点上氨基酸325的多态性决定了其自身抗体多肽的特异性。ZnT8自身抗体可以在新发T1DM和糖尿病前期患者血清中检测出,在T1DM患者血清中其他自身抗体（谷氨酸脱羧酶抗体、抗酪氨酸磷酸酶抗体、抗胰岛素抗体和抗胰岛细胞抗体）阴性时ZnT8抗体仍有26％的阳性率。对自身抗体ZnT8的检测有助于在人群中筛查糖尿病前期患者,因此检测ZnT8抗体对评估T1DM的发生发展是必要的,ZnT8（SLC30A8）是T1DM的一个重要并独立的预测因子。     

自身抗体与1a型糖尿病的诊断和预测

1a型和1b型糖尿病最重要的区别是前者存在胰岛自身抗体。本文主要就自身免疫性1型糖尿病的两个主要问题进行阐述：①哪些抗体可作为自身免疫性1型糖尿病的诊断标志;②用于诊断1型糖尿病的胰岛自身抗体能否预测非糖尿病患者群的1型糖尿病的发生。     

1型糖尿病与HLA-DQB1基因及自身抗体相关性研究

采用基因分型技术,确定32例1型糖尿病患者及23例正常对照的HLA-DQB1等位基因.用酶联免疫吸附法测定血清中谷氨酸脱羧酶抗体(GADA)、胰岛细胞抗体(ICA)及胰岛素自身抗体(IAA).结果在1型患者中,DQB1*0201、*0303、*0604等位基因频率显著高于对照(P＜0.05),DQB1*0301则低于对照(P＜0.05),其余DQB1等无显著性差异.等位基因为DQB1*0201的患者中GADA阳性率显著高于阴性率.结论在中国汉族人群中,DQB1*0201、*0303、*0604是1型糖尿病易感性等位基因,DQB1*0301是1型糖尿病保护性等位基因.DQB1*0201可能对GADA的产生起允许作用.     

锌转运体8自身抗体的放射配体检测法

目的建立锌转运体8自身抗体（ZnT8A）的放射配体检测法（RLA）。方法采用重组人ZnT8质粒,经试管内转录与翻译,获得“S-ZnT8抗原,35S-ZnT8与血清在自制旋转孵育器上旋转温育后,用蛋白A-琼脂糖沉淀免疫复合物。免疫复合物经TBST缓冲液洗涤后,用多功能闪烁发光分析仪检测沉淀物放射性计数值。参加国际糖尿病免疫学会（IDS）和美国疾病预防控制中心联合举办的第六次糖尿病自身抗体国际标准化评估（DAsP2009）,评价该方法的敏感性和特异性。检测429例1型、855例2型糖尿病患者以及405例正常人ZnT8A水平,初步评价其临床应用价值。结果该方法批内CV3．9N～9．8N,批间CV4．3％～13．8％;DASP2009显示,该方法敏感性66％,特异性100％。受试者操作特性曲线（ROC）分析显示,曲线下面积为0．879±0．034;该方法阳性阈值ZnT8A指数为0．011（405名正常人的99％百分位点）,检测1型糖尿病患者阳性率24．0％,高于初诊2型糖尿病患者1．3％和健康人0．99％（P均do．01）。结论建立的RLA法检测ZnT8A敏感性高、特异性强、重复性好,可应用于自身免疫糖尿病的诊断与分型。     

Distribution of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8 in type 1 diabetes and latent autoimmune diabetes: A nationwide,multicentre, cross-sectional study

Aims

This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies' association with clinical characteristics and HLA-DR-DQ genes.

Materials and Methods

This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency.

Results

IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD.

Conclusions

IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.

     

Prevalence of diabetes-associated autoantibodies among patients presenting with type 2 diabetes and related metabolic differences

BackgroundTo explores the prevalence of autoantibodies (zinc transporter 8 autoantibodies (ZnT8A), antibodies to insulin (IAAs), glutamic acid decarboxylase autoantibody (GAD65)), the relation of the type of positive autoantibody and the number of positive autoantibodies with the glycemic and lipid profile of the patients with LADA (Latent Autoimmune Diabetes in Adults) and compares it to the metabolic profile of patients presenting with type 2 diabetes (T2DM).Methods263 patients with T2DM were recruited for this cross-sectional study in Tehran, Iran. Data from patients included complete medical history, GAD65, ZnT8A, IAA and routine metabolic laboratory workup. Assay for autoantibodies were conducted using ELISA kits. The association between autoantibodies and glycemic and lipid profile of patients with diabetes was assessed using univariate and multivariate regression analysis.ResultsOur study revealed that among 263 patients with T2DM, 29 (11%) cases were positive for IAAs, 9 (3.4%) for ZnT8A, and 12 (4.6%) for GAD65. Six (2.3%) of the patients had triple positive antibodies. Patients with positive results were younger, had lower body mass index (BMI), c-peptide, triglyceride, low-density lipoprotein (LDL), and higher high-density lipoprotein (HDL), HbA1c and fasting blood glucose (FBG) levels. Triple antibody positivity was significantly associated with lower levels of C-Peptide, Triglycerides, FBG, and HbA1c compared to triple negative antibodies.ConclusionPatients with LADA positive for either of the autoantibodies (GAD65, ZnT8 and IAA) presented with worse glycemic control. Measurement of these autoantibodies can assist in discrimination of these patients and help with earlier control of glycemic profile.     

1型糖尿病患者的临床特点和多种胰岛自身抗体检出情况

目的分析1型糖尿病（T1DM）患者多种胰岛自身抗体的检出情况和不同类型T1DM的临床特征。方法选取2010年11月至2011年11月在中日友好医院住院的67例T1DM患者,分析其临床特征及胰岛细胞抗体（ICA）、胰岛素抗体（IAA）、谷氨酸脱羧酶抗体（GADA）[酶联免疫吸附试验（ELISA）法和免疫沉淀法（RIP）检测]、蛋白酪氨酸磷酸酶抗体（IA2A）和锌转运蛋白8抗体（ZnT8A）等6种胰岛自身抗体情况。结果本组T1DM共67例,其中经典型T1DM53例,成人迟发性自身免疫糖尿病（LADA）12例和暴发性1型糖尿病（FT1D）2例。起病年龄2～77岁,体质指数（BMI）（22±4）kg／m2,糖化血红蛋白（HbAlc）9．7％±2．4％,空腹C肽（0．3±O．4）μ／L。GADA（ELISA）阳性51例（76．1％）,GADA（RIP）阳性35例（52．2％）,IA2A阳性19例（28．3％）,ZnT8A阳性16例（23．9％）,IAA阳性16例（23．9％）,ICA阳性10例（14．3％）。前4种抗体检测方法至少1种阳性者共56例（83．6％）。51例ELISA法GADA阳性包括了35例RIP检测GADA阳性中的33例、19例IA2A阳性中15例及16例ZnT8A阳性中的14例。经典1型糖尿病在发病初至半年内需要胰岛素治疗,而LADA平均在发病3．9年后需要胰岛素治疗。2例FT1D患者起病急,发病时血糖分别为41．1和23．1mmol／L,HbAlc分别为7．8％和6．5％,空腹及餐后血C肽均小于0．03μg／L或不能测出。结论ELISA检0n．0GADA对1型糖尿病的诊断有较高敏感性,联合多种抗体检测对T1DM诊断作用有限。FT1D起病急骤,代谢紊乱更为严重。     

暴发性1型糖尿病的患病状况及其特征

目的 探讨暴发性1型糖尿病(F1D)的患病状况和临床特征.方法 采用Hanafusa提出的诊断标准,从中南大学湘雅二医院急性酮症起病的1型糖尿病患者中筛选F1D患者,再根据胰岛自身抗体谷氨酸脱羧酶抗体(GADA)或蛋白酪氨酸磷酸酶抗体的有无将非F1D患者分为经典1型组和特发1型组,比较3组患者临床特征的差异.结果 87例急性酮症起病的1犁糖尿病患者中有8例符合F1D的诊断标准,占9.1%,在18岁以上患者中占14.0%.起病时暴发组的血糖显著高于经典1型组和特发1型组(P=0.004);暴发组血淀粉酶水平显著高于经典1型组(P=0.021).4例(50%)患者发病初期GADA阳性,其中1例柯萨奇病毒B(CVB)IgM阳性,1例人单纯疱疹病毒1(HSV1)IgM阳性.结论 F1D约占以酮症或酮症酸中毒起病的1型糖尿病患者的10%.起病时F1D患者比经典1型和特发1型糖尿病患者有更严重的代谢紊乱.病毒感染和自身免疫可能参与其发病过程.     

Factors predicting clinical remission in adult patients with type 1 diabetes

OBJECTIVES: To describe the course of clinical remission in adult patients (16-50 years of age) with type 1 diabetes and to identify factors predictive of the occurrence and length of remission. DESIGN: A retrospective cohort study. SUBJECTS: Sixty-two consecutive patients (43 men and 19 women) with new onset IDDM, 27 +/- 8 years at diagnosis and treated with multiple insulin injections from the beginning. SETTING: Department of Medicine, Uppsala University Hospital and Orebro Medical Centre, Sweden. MAIN OUTCOME MEASURES: Length and occurrence of remission (defined as maintenance of HbA1c < or = 6.5% and an insulin dosage of < or = 0.4 U kg-1 day-1 for a minimum of 1 month) in relation to nine biochemical and clinical factors at diagnosis. RESULTS: Sixty-one per cent of the patients entered remission. The duration of remission was longer in males than females (10 +/- 12 vs. 2 +/- 3 months; P < 0.01). Male gender, normal serum bicarbonate at onset and a short time of classic symptoms before onset were predictive markers (P < 0.01; P < 0.05 and P < 0.01, respectively) for longer duration of remission. Low serum bicarbonate levels at onset were associated with lower occurrence of remission. Blood glucose, body mass index (BMI), and age at diagnosis did not influence the occurrence or the duration of remission. CONCLUSIONS: In most adult patients with new onset of type 1 diabetes remission is induced when using multiple insulin injection therapy. Male patients seem particularly prone to remission, and the length and extent of beta-cell strain prior to diagnosis strongly influences its course.