青少年与成人期发病的1型糖尿病异质性研究

目的 探讨青少年与成人期发病的1型糖尿病患者临床表现、自身免疫和遗传学异质性.方法 2002年6月至2003年12月就诊于哈尔滨医科大学附属第二医院内分泌科的34例青少年发病(发病年龄≤25岁)和53例成人发病(发病年龄＞25岁)1型糖尿病患者,比较其主要临床特点,自身抗体的阳性率和水平,并用聚合酶链式反应-顺序特异性探针方法(PCR-SSP)检测患者的人白细胞抗原(HLA)上不同等位基因的频率.结果 (1)在临床表现方面,两组患者中成人患者以葡萄糖刺激后2 h C肽(2 hCP)较高,体重指数(BMI)和腰臀围比(WHR)较大,甘油三酯(TG)较高;(2)血清免疫学方面,青少年患者血清蛋白酪氨酸磷酸酯酶样蛋白抗体(IA2-Ab)水平明显高于成人患者(P＜0.01),其它抗体在两组间差异无显著性;(3)遗传学方面,HLA-DQB1*0201频率在成人发病患者中低于青少年发病患者(13.2%对58.8%,P＜0.01),携带HLA-DQB1*0201的患者IA2-Ab水平较高.结论 与青少年发病的1型糖尿病患者比较,成人发病患者具有较好的胰岛功能和更多的2型糖尿病表型特征,HLA-DQB1*0201和IA2-Ab可能在决定青少年和成人患者的临床异质性方面起核心作用.     

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。     

胰岛自身抗体异质性研究进展

在胰岛自身抗体检测方法日趋完善和标准化的同时,人们在研究中发现,有的自身抗体阳性个体能快速进展为1型糖尿病(T1DM),而其他拥有相似抗体状况(类型和滴度)的个体却在多年内不受影响,甚至终身不发病[1-2].这些研究提示,除了与抗体的"量"因素影响外,"质"也同时起作重要作用.本文从目前国际上采用的研究技术进行分类,综述近年谷氨酸脱羧酶(GAD65)和蛋白酪氨酸磷酸酶(IA-2)自身抗体异质性的研究进展.     

爆发性1型糖尿病患者谷氨酸脱羧酶抗体阳性一例报道

爆发性1型糖尿病(FT1DM)是T1DM亚型,临床少见,发展迅速,病情凶险,死亡率高,多数FT1DM患者胰岛相关抗体阴性.现报告1例FT1DM GADAb阳性患者.     

IA-2A与GADA检测对1型糖尿病的诊断价值

目的了解蛋白酪氨酸磷酸酶抗体(IA-2A)与谷氨酸脱羧酶抗体(GADA)在1型糖尿病(DM)中的检出率及其诊断价值.方法采用放射配体法检测114例1型DM患者及188名正常对照者IA-2A与GADA水平,并以放免法检测1型DM患者空腹C肽(FCP)、甲状腺球蛋白抗体(TGAb)与甲状腺过氧化物酶抗体(TPOAb)水平.结果(1)1型DM患者中GADA、IA-2A检出率分别为49.1%(56/114)和24.6%(28/114),高于正常对照1.1%与0.6%(均P＜0.01).15岁以下、病程≤0.5年的1型DM患者GADA、IA-2A检出率分别为66.7%(8/12)和58.3%(7/12),与白种人(56.0%～82.0%与56.4%～74.4%)比较,GADA差异无显著性;而IA-2A仅低于检出率最高的国家芬兰(85.7%,P＜0.01);(2)15岁以下与15岁以上1型DM组GADA阳性率分别为61.8%(21/34)和43.8%(35/80,P＞0.05);而IA-2A阳性率分别为41.2%(14/34)和17.5%(14/80,P＜0.01).病程1年以内与病程1年以上1型DM患者GADA阳性率分别为56.4%(31/55)与42.4%(25/59,P＞0.05);而IA-2A阳性率分别为34.5%(19/55)对15.2%(9/59,P＜0.05);(3)1型DM中GADA和IA-2A阳性患者与GADA和IA-2A阴性患者比较,FCP水平较低(均P＜0.01);(4)单纯GADA阳性患者中甲状腺自身抗体检出率为38.5%(15/39),高于单纯IA-2A阳性患者的0%(0/9,P＜0.05);(5)1型DM患者IA-2A与GADA联合检测检出率为58.8%,而病程1年内1型DM患者达69.1%,均高于IA-2A单一抗体检测的阳性率(P＜0.01).结论(1)中国儿童新发1型DM患者IA-2A与GADA检出率与欧美白种人接近;IA-2A阳性率受发病年龄及病程影响较大,而GADA受其影响小;(2)GADA或IA-2A阳性预示1型DM患者胰岛β细胞功能更差;IA-2A是一个比GADA更特异的胰岛自身免疫指标;(3)GADA和IA-2A联合检测可提高自身免疫性1型DM诊断的敏感性.     

1型糖尿病自身抗原的研究进展及其意义

胰岛素（INS）、谷氨酸脱羧酶65（GAD65）、胰岛细胞瘤相关蛋白2（IA－2）和IA－2β是已发现的1型糖尿病（T1DM）的主要自身抗原，它们不仅是体液性自身免疫反应的靶蛋白，而且可能也是自身反应性T淋巴细胞的靶分子。针对这些自身抗原的自身抗体的存在，有助于糖尿病的正确分型及T1DM的预测。INS和GAD65成为T1DM免疫干预疗法的主要靶点。     

肠道病毒感染与1型糖尿病

1型糖尿病与肠道病毒感染密切相关。多数病毒通过诱发自身免疫而致病,其机制有分子相似性和旁路激活学说。前者证实,病毒的非结构蛋白2C有6个氨基酸序列与谷氨酸脱羧酶抗原相同,故能诱发自身免疫破坏;后者认为,感染导致胰腺外分泌组织炎症,激活休眠的T细胞而诱发免疫反应。研究证实,病毒诱发自身免疫反应要在一定数量的自主反应性T细胞及胰岛感染存在的前提下才会发生,在糖尿病出现临床症状几年前,β-细胞破坏就已经开始。     

Body composition in adolescent girls with type 1 diabetes.

AIMS: To compare body composition in adolescent girls with Type 1 diabetes with healthy controls. RESEARCH DESIGN AND METHODS: In this population-based study, body composition was examined, using dual-energy X-ray absorptiometry (DXA) and skinfold measurements, in 18 adolescent post-menarcheal females, 16-19 years of age, with Type 1 diabetes since childhood in comparison to age-matched healthy control subjects. RESULTS: Body mass index was 2.7 kg/m2 higher in diabetic patients (26.3 +/- 2.6 vs. 23.6 +/- 3.8; P < 0.05). The overweight consisted almost entirely of increased fat mass, as evaluated by both skinfold measurements and DXA. Bone mineral density did not differ between the two groups. In diabetic females, the distribution of the fat mass was increased in the upper part of the body. The fat distribution, expressed as the abdominal-to-leg ratio, was significantly correlated to glycated haemoglobin (HbA1c) (r = 0.69; P < 0.005), daily dosage of insulin expressed per kilogram body weight (r = 0.78; P < 0.0005) and total cholesterol (r = 0.60; P < 0.001). CONCLUSIONS: The observed overweight in adolescent females with Type 1 diabetes is explained by an increased fat mass. Abdominal fat accumulation was associated with poor glycaemic control, increased need for insulin and elevated blood lipids.     

The lived experience of adolescent females with type 1 diabetes

PURPOSE: The purpose of this study was to gain a better understanding of what it means for adolescent females to live with type 1 diabetes. METHODS: Van Manen's phenomenological framework was used to guide the project of inquiry. Adolescents were recruited from a diabetes camp. A purposive sample of 10 adolescent females, aged 16 and 17 years, volunteered to participate in the study. Unstructured, one-on-one interviews were conducted and participants' accounts were transcribed and analyzed for themes. RESULTS: Five themes were identified: (1) blending in with the adolescent culture, (2) standing out and being watched, (3) weighing the options and making choices, (4) being tethered to the system and to diabetes, and (5) struggling with conflicts. These adolescent females struggled with several conflicts and choices they were forced to make on a daily basis. They felt tethered to a disease that would never go away and to the healthcare system. Yet, they adopted ways to handle their disease so that it was manageable within the context of their lives. Fitting in with their peers was often more important than diabetes management. CONCLUSIONS: Making visible the experience of adolescent females living with type 1 diabetes has implications for practice, education, and research in diabetes education.     

Complications of pediatric and adolescent type 1 diabetes mellitus

Type 1 diabetes mellitus is potentially associated with serious microvascular and macrovascular complications, although these are usually subclinical during the pediatric and adolescent years. There is no “grace” period for the beginnings of such complications. Duration of diabetes, glycemic control, age, and pubertal stage are critical factors contributing toward development of such problems. Other risk factors include family history (genetic predisposition), hyperlipidemia, hypertension, and smoking. The Diabetes Control and Complications Trial (DCCT) proved the importance of glycemic control and emphasized the ability of improved glucose control to prevent or decrease retinopathy, nephropathy, and neuropathy using a multidisciplinary same-philosophyof-care approach plus targeted glucose and hemoglobin A_1c values. Other natural history and intervention studies support the findings of the DCCT. Although our current tools are not perfect, they allow us to decrease microangiopathic complications very significantly if we educate our patients and their family members. Metabolic control counts.     

1型糖尿病起病过程的临床异质性分析

目的 了解1型糖尿病起病过程的临床异质性.方法 回顾性分析自1999年1月至2009年12月广州中山大学附属第一医院内分泌科205例新诊断1型糖尿病患者的临床资料.根据症状出现至就诊时间,将患者分为暴发性1型糖尿病（FT1DM）、急性起病及缓慢起病的1型糖尿病（出现症状至就诊时间分别≤或＞3个月）,比较3组患者临床特点及实验室检查资料.血清谷氨酸脱羧酶抗体（GADA）、胰岛细胞自身抗体（ICA）、胰岛素自身抗体（IAA）均为定性检测,GADA采用酶联免疫吸附法（ELISA）,ICA、IAA及血清C肽检测采用放射免疫法.计量资料采用单因素方差分析或两个独立样本的t检验,计数资料采用多变量卡方检验及Fisher精确概率法进行统计分析.结果 FT1DM、急性起病及缓慢起病的1型糖尿病分别占8.8%、66.8%及24.4%.3组中FT1DM患者血糖升高更明显[分别为（31±12）、（25±10）、（24±8）mmol/L,F=4.462,P＜0.05],而糖化血红蛋白略高于正常[分别为（6.8±1.1）%、（12.3±2.4）%、（13.9±2.7）%,F=54.661,P＜0.05],酮症酸中毒更常见（分别为93.8%、45.3%、8.0%,F=44.943,P=0.000）,合并低钠血症、高钾血症、酸中毒、肝肾功能受损更严重,合并妊娠的比例更高（分别为22.2%、0、0,X2=20.982,P=0.000）.缓慢起病的1型糖尿病患者起病年龄及体质指数较另两组大,而体质量下降更明显,负荷后C肽水平明显高于另外两组[分别为（0.40±0.36）、（0.10±0.13）、（0.34±0.26）nmol/L,F=8.752,P＜0.05].儿童及青少年在急性起病的1型糖尿病中所占比例更高,其临床表型与成人相似.结论3组患者起病过程的临床异质性十分明显,提示1型糖尿病可能存在不同的疾病触发机制.     

The spectrum of thyroid disorders in adult type 1 diabetes mellitus

BACKGROUND: Thyroid disorders such as goiter, nodules, autoimmune thyroid disease and thyroid dysfunction have rarely been investigated in adult type 1 diabetes mellitus. Our aim was to study the spectrum of thyroid disorders in adult type 1 diabetic subjects and compare them with results obtained from a sample of the general adult population. METHODS: The study population comprised 224 type 1 diabetic and 3481 non-diabetic subjects aged 20-69 years. Thyroid function (TSH, FT3 and FT4) and serum autoantibodies to thyroperoxidase (anti-TPO-Ab) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. RESULTS: Type 1 diabetic subjects had a higher risk of known thyroid disease [odds ratio (OR) 1.78, 95% confidence interval (CI) 1.11-2.85], a lower risk of goiter (OR 0.73; 95%-CI 0.54-0.99) and nodules (OR 0.54; 95%-CI 0.35-0.85), and a higher risk of anti-TPO-Ab >200 IU/mL (OR 1.94; 95%-CI 1.28-2.95) compared to the reference population. Furthermore, diabetic subjects had lower serum FT3 levels than the non-diabetic references (adjusted mean 5.00 pmol/L; 95%-CI 4.88-5.12 pmol/L versus 5.27 pmol/L; 95%-CI 5.24-5.30 pmol/L). CONCLUSIONS: Adult type 1 diabetes mellitus is associated with a decreased risk of goiter and nodules and an increased risk of thyroid autoimmunity. A diabetes-related low T3 syndrome may contribute to the differences in thyroid function between type 1 diabetic and non-diabetic subjects.     

IGRP与1型糖尿病的关系

1型糖尿病是由T细胞介导的自身免疫性疾病.许多研究表明,抗原特异性的CD4~+和CD8~+T细胞在1型糖尿病的发病过程中起重要作用.胰岛细胞特异性葡萄糖-6-磷酸酶催化亚基相关蛋白(IGRP)作为1型糖尿病的主要自身抗原之一,是葡萄糖-6-磷酸酶蛋白家族中的一员,在人和非肥胖糖尿病鼠胰腺中均有表达.它在胰岛β细胞的代谢过程中起重要作用,但是确切机制仍不清楚.IGRP的研究将有助于探索1型糖尿病诊断和治疗的新方法.     

IGRP与1型糖尿病的关系

Type 1 diabetes is a T cell-mediated autoimmune disease. Many studies have suggested that both CD4~+ and CD8~+ T cells are involved in the pathogenesis of type 1 diabetes. Islet-specific glucose-6-phosphatase catalytic subunit related peptide (IGRP) ,which is recognized as a major autoantigen for autoim-mune type 1 diabetes, is a member of the glucose-6-phosphatsse family. IGRP is expressed in the pancreas of both human and NOD mice and is thought to have a role in islet β cell metabolism. However,its exact func-tion has not yet been defined. The research of IGRP will help to explore new methods of the diagnosis and treatment of type 1 diabetes.