Diabetes Perdiction in Skane(DiPiS)

斯科讷糖尿病预测(DiPiS)

• 批准号: 6839964
• 负责人: AKE LERNMARK
• 金额: $ 61.15万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6839964
• 关键词: clinical research

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.

描述（由申请人提供）： 1型糖尿病（T1DM）在遗传易感的个体中发展。与环境因素有很强的疾病联系，被认为会引发疾病。该疾病的发病机理取决于自身免疫现象，涉及β细胞中几种自身抗原的细胞和体液免疫反应。该疾病的前途较长，并且出现GAD65，IA-2或胰岛素自身抗体可以预测疾病。在本研究中 - Skane（DIPIS）中的糖尿病预测，我们将对所有新生儿（每年约10,000名儿童）进行高风险HLA和其他TIDM遗传因素。针对GAD65，IA-2和胰岛素的胰岛细胞自身抗体将在出生时和随访期间进行分析，以识别环境触发因素。特别是，我们将检验以下假设：妊娠不良事件代表胰岛自动免疫的触发因素，该触发会发展为1型糖尿病，但仅在某些易感性受试者中。具体目的是：1）筛查瑞典南部地区Skane的所有新生婴儿，有120万居民； 2）分析1型糖尿病的脐带血高风险HLA等位基因和三种胰岛细胞自身抗体，GAD65AB，IAA和IA-2AB； 3）分析传染病的历史，妊娠不良事件和心理社会因素，作为1型糖尿病风险的加性或增强因素以及怀孕期间病毒PCR和血清学的风险； 4）在出生时，自身抗体时，自身抗体，IA-2和胰岛素的自身抗体的同种型，亚型和表位特异性，在自身抗体的第一次出现以及诊断为1型糖尿病时； 5）确定健康母亲出生的自身免疫性暴露阳性的健康母亲的自身反应性T细胞，以及6）将关键数据提交给数据协调中心（DCC），以有效地识别1型糖尿病的环境触发因素。长期目标是确定妊娠感染或其他不良事件和心理因素的作用，这些因素增加了遗传易感儿童中1型糖尿病的风险。了解遗传风险与环境风险因素之间的相互作用可能使制定策略减少暴露量，从而最大程度地减少糖尿病风险。