Diabetes Perdiction in Skane(DiPiS)

描述（由申请人提供）： 1型糖尿病（T1 DM）发生于遗传易感个体。有一个强烈的疾病与环境因素，这被认为是引发疾病。该疾病的发病机制依赖于自身免疫现象，涉及直接针对β细胞中的几种自身抗原的细胞和体液免疫应答。该疾病具有长前驱症状，并且GAD 65、IA-2或胰岛素自身抗体的出现预示疾病。在目前的研究--Skane糖尿病预测（DiPiS）中，我们将对所有新生儿（每年约10000名儿童）进行高风险HLA和其他TIDM遗传因素的筛查。将在出生时和随访期间分析针对GAD 65、IA-2和胰岛素的胰岛细胞自身抗体，以确定环境触发因素。特别是，我们将测试的假设，妊娠不良事件代表触发胰岛自身免疫，将进展为1型糖尿病，但只有在一些易感的科目。具体目标是：1）筛查瑞典南部地区Skane的所有新生儿，Skane有120万居民; 2）分析脐带血中的1型糖尿病高危HLA等位基因和三种胰岛细胞自身抗体，GAD 65 Ab，IAA和IA-2 Ab; 3）分析感染史，妊娠期不良事件和心理社会因素与妊娠期病毒PCR和血清学一起作为1型糖尿病风险的附加或增强因素; 4）在出生时、首次出现自身抗体时和诊断1型糖尿病时确定针对GAD 65、IA-2和胰岛素的自身抗体的同种型、亚型和表位特异性; 5）确定自身抗体阳性的健康母亲所生的新生儿中的自身抗原反应性T细胞作为自身免疫暴露的证据，以及6）向数据协调中心（DCC）提交关键数据，以有效识别1型糖尿病的环境触发因素。长期目标是确定妊娠期感染或其他不良事件和心理因素在增加遗传易感儿童1型糖尿病风险中的作用。了解遗传风险和环境风险因素之间的相互作用可能有助于制定减少暴露的策略，从而最大限度地降低糖尿病风险。

DESCRIPTION (provided by applicant): Type 1 diabetes mellitus (T1DM) develops in genetically susceptible individuals. There is a strong disease association with environmental factors, which are thought to trigger the disease. The disease pathogenesis is dependent on autoimmune phenomena involving both the cellular and humoral immune response direct against several autoantigens in the beta cells. The disease has a long prodrome and the appearance of GAD65, IA-2 or insulin autoantibodies predict disease. In the present study - Diabetes Prediction in Skane (DiPiS) we will screen all newborns (about 10, 000 children per year) for high risk HLA and other TIDM genetic factors. Islet cell autoantibodies against GAD65, IA-2 and insulin will be analyzed at birth and during follow-up to identify environmental triggers. In particular, we will test the hypothesis that gestational adverse events represents triggers of islet autoimmunity that will progress to type 1 diabetes but only in some susceptible subjects. The Specific aims are: 1) to screen all newborn babies in Skane, the southern region of Sweden with 1.2 million inhabitants; 2) to analyze the cord blood for type 1 diabetes high risk HLA alleles and for the three islet cell autoantibodies, GAD65Ab, IAA and IA-2Ab; 3) to analyze infectious history, gestational adverse events and psychosocial factors as additive or potentiating factors to type 1 diabetes risk along with virus PCR and serology during pregnancy; 4) to define isotype, subtype and epitope specificities of autoantibodies to GAD65, IA-2 and insulin at birth, at the first appearance of autoantibodies and at diagnosis of type 1 diabetes; 5) to determine autoantigen reactive T cells in neonates born to healthy mothers positive for autoantibodies as evidence of autoimmunity exposure and 6) to submit critical data to the Data Coordinating Center (DCC) to effectively identify environmental triggers of type 1 diabetes. The long-term objective is to identify the role of gestational infections or other adverse events and psychological factors that increase the risk for type 1 diabetes in genetically susceptible children. Understanding the interaction between genetic risk and environmental risk factors may permit the development of strategies to reduced exposure and thereby minimize diabetes risk.