Natural History of Pre-diabetic Autoimmunity (DAISY)

这项名为《青少年糖尿病自身免疫研究》(DAISY)的项目始于1993年7月，使我们得以建立 两个独特的幼儿队列，他们患1型糖尿病的风险增加了20倍：1)队列中有693人 1型糖尿病患者及其1007名亲属的兄弟姐妹和子女(目前年龄中位数为4.5岁)；以及2) 1,069名新生儿(目前年龄中位数3.1岁)与1型糖尿病相关的HLA-DR，DQ等位基因已确定的队列 通过对21,713名没有糖尿病亲属的普通人群儿童及其1,491名亲属进行脐带血筛查。 到目前为止，对这些队列的短期前瞻性跟踪已经提供了关于 儿童早期b细胞自身免疫与糖尿病的自然病史。基于我们的发现，我们建议遵循 这些队列经历了b细胞自身免疫风险最高的时期，并解决了以下目标： 具体目标 1.继续登记和跟踪，直至10岁的中位数，现有的兄弟姐妹/子女和 通过普通人群的HLA-DR、DQ筛查发现具有高和中等遗传风险的新生儿：a)以前的定义 按年龄、种族/民族、人类白细胞抗原基因型别和1型糖尿病家族史分类的b细胞自身免疫发生率；b)正式 评估所有参与者可用的候选自身免疫/糖尿病风险因素，例如，报告的儿童早期饮食 感染和疫苗接种；以及c)维持这一人口实验室，以进行1型糖尿病和其他疾病的进一步研究 自身免疫性疾病。 2.继续现有的和启动新的病例对照研究，这些研究嵌套在选定的环境和遗传的队列中 危险因素：a)b细胞自身免疫及其持久性；b)从b细胞自身免疫进展到糖尿病 3.根据我们的发现，从80名高危儿童出生开始进行密集随访(人类白细胞抗原-DR3/4，DQB1*0302 除每三个月去一次诊所外，还提供每月滤纸血样和每周粪便样本。 4.采用病例对照和病例亲子分析相结合的方法探讨基因与环境的交互作用。 我们的研究正在填补对导致儿童早期1型糖尿病事件的理解的重要空白 提供对b细胞自身免疫发病率和相关相对风险的第一次无偏人群估计 有候选的环境和遗传因素。

This project, called Diabetes AutoimmunityStudy in the Young (DAISY) began in July 1993 and allowed us to establish two unique cohorts of very young children who are at up to 20-fold increased risk of type 1 diabetes: 1) a cohort of 693 siblings and offspring (current median age 4.5 years) of persons with type 1 diabetes and 1007 of their relatives; and 2) a cohort of 1,069newborns (current median age 3.1 years) with type 1 diabetes-associated HLA-DR,DQ alleles, identified through a cord blood screening of 21,713 general population children without a diabetic relative and 1,491 of their relatives. To date, a short prospective follow-up of these cohorts has already provided new important information concerning the natural history of b-cell autoimmunity and diabetes in early childhood. Based on our findings, we are proposing to follow these cohorts through the period of the highest risk of b-cell autoimmunity and to address the following goals: Specific Aims 1. To continue enrollment and follow-up, until the median age of 10yrs,of the existing cohorts of siblings/offspring and of newborns at high and moderate genetic risk detected through general population HLA-DR,DQ screening to: a) former define the incidence of b-cell autoimmunityby age,race/ethnicity, HLA-genotype, and family history of type 1 diabetes; b) formally evaluate candidate autoimmunity/diabetes risk factors available for all participants, e.g., early childhood diet, reported infections, and vaccination; and c) sustain this population laboratory for additional studies of type 1 diabetes and other autoimmune diseases. 2. To continue current and initiate new case-control studies, nested in the cohorts, of selected environmental and genetic risk factors for: a) b-cell autoimmunityand its persistence; and b) progression from b-cell autoimmunityto diabetes 3. Based on our findings, initiate intensive follow-up from birth of eighty highest risk children (HLA-DR3/4,DQB1 *0302 relatives) with monthly filter paper blood samples and weekly stool samples in addition to tri-monthly clinic visits. 4. To explore gene-environment interactions using combined approaches of case-control and case parent analyses. Our study is filling important gaps in the understanding of the events leading to type 1 diabetes in early childhood by providing the first unbiased population estimates of the incidence of b-cell autoimmunityand of the relative risks associated with candidate environmental and genetic factors.