Diabetes Perdiction in Skane(DiPiS)

斯科讷糖尿病预测(DiPiS)

• 批准号: 7220024
• 负责人: AKE LERNMARK
• 金额: $ 73.4万
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7220024
• 关键词: Diabetes; Perdiction; Skane; DiPiS

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 SkSne, 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 i long-term objective is to identify the role of gestational infections or other adverse events and i 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.

1 型糖尿病 (T1DM) 发生在遗传易感人群中。有一种强烈的 疾病与环境因素有关，环境因素被认为会引发疾病。这 疾病的发病机制取决于涉及细胞和免疫系统的自身免疫现象 体液免疫反应直接针对β细胞中的几种自身抗原。该病有一个 长前驱症状和 GAD65、IA-2 或胰岛素自身抗体的出现可预测疾病。在 目前的研究 - Skane 糖尿病预测 (DiPiS) 我们将对所有新生儿（约 10, 000 每年儿童）的高风险 HLA 和其他 TIDM 遗传因素。胰岛细胞自身抗体 针对 GAD65、IA-2 和胰岛素的抗体将在出生时和随访期间进行分析，以确定 环境触发因素。特别是，我们将检验妊娠不良事件的假设 代表胰岛自身免疫的触发因素，会进展为 1 型糖尿病，但仅在某些情况下 易感对象。具体目标是： 1) 对南部 SkSne 的所有新生儿进行筛查 拥有 120 万居民的瑞典地区； 2) 分析脐带血是否存在 1 型糖尿病 高风险 HLA 等位基因以及三种胰岛细胞自身抗体 GAD65Ab、IAA 和 IA-2Ab； 3）到 分析感染史、妊娠不良事件和心理社会因素作为附加或 妊娠期间 1 型糖尿病风险的增强因素以及病毒 PCR 和血清学检查； 4) 定义GAD65、IA-2和胰岛素自身抗体的同种型、亚型和表位特异性 出生时、首次出现自身抗体时以及诊断 1 型糖尿病时； 5）到 确定健康母亲所生新生儿的自身抗原反应性 T 细胞 自身抗体作为自身免疫暴露的证据，并且 6) 向数据提交关键数据 协调中心 (DCC) 有效识别 1 型糖尿病的环境诱因。我 长期目标是确定妊娠感染或其他不良事件的作用，并且我 增加遗传易感儿童患 1 型糖尿病风险的心理因素。 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 制定减少接触的策略，从而最大限度地降低糖尿病风险。