Natural History of Pre-diabetic Autoimmunity (DAISY)

这个名为“年轻人糖尿病自身免疫研究”（DAISY）的项目始于1993年7月， 两个独特的年龄很小的儿童队列，他们患1型糖尿病的风险增加了20倍：1）693人的队列 1型糖尿病患者及其亲属的兄弟姐妹和后代（目前的中位年龄为4.5岁）;以及2）a 1,069名新生儿（当前中位年龄3.1岁）的队列研究，确定了1型糖尿病相关的HLA-DR、DQ等位基因 通过对21 713名无糖尿病亲属的普通儿童及其1 491名亲属进行脐带血筛查。 迄今为止，对这些队列进行的短期前瞻性随访已经提供了关于 儿童早期B细胞自身免疫和糖尿病的自然史。根据我们的调查结果，我们建议 这些队列通过b细胞自身免疫的最高风险期，并解决以下目标： 具体目标 1.继续招募和随访现有的兄弟姐妹/后代队列和 通过一般人群HLA-DR、DQ筛查检测到高和中等遗传风险的新生儿，以：a）前者定义 b细胞自身免疫的发生率与年龄、人种/种族、HLA基因型和1型糖尿病家族史有关; 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，幼儿饮食，据报道， 感染和疫苗接种;以及c）维持这一人口实验室，用于1型糖尿病和其他 自身免疫性疾病 2.继续当前的并启动新的病例对照研究，嵌套在队列中，对选定的环境和遗传 风险因素：a）b细胞自身免疫及其持续性;和B）从b细胞自身免疫发展为糖尿病 3.根据我们的研究结果，从80名高危儿童（HLA-DR 3/4，DQB 1 *0302）出生起开始密集随访 除了每三个月一次的门诊访视外，还每月采集滤纸血样，每周采集粪便样本。 4.采用病例对照和病例亲本分析相结合的方法探讨基因-环境相互作用。 我们的研究填补了对导致儿童早期1型糖尿病的事件的理解方面的重要空白， 提供了B细胞自身免疫发生率和相关风险的第一个无偏人群估计值， 与候选环境和遗传因素。

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.