Diabetes Prediction in Skane(DiPiS)

斯科讷糖尿病预测(DiPiS)

• 批准号: 6587903
• 负责人: AKE LERNMARK
• 金额: $ 100万
• 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/6587903
• 关键词: Scandinavian country; autoantibody; child (0-11); clinical chemistry; clinical research; cooperative study; diabetes mellitus genetics; diabetes risk; disease /disorder etiology; early experience; embryo /fetus toxicology; environmental stressor; gene environment interaction; genetic susceptibility; histocompatibility typing; human pregnant subject; human subject; insulin dependent diabetes mellitus; longitudinal human study; mass screening; prediabetic state

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) 发生在遗传易感人群中。疾病与环境因素有很强的相关性，环境因素被认为是引发疾病的原因。该疾病的发病机制取决于自身免疫现象，涉及直接针对β细胞中几种自身抗原的细胞和体液免疫反应。该疾病有较长的前驱症状，GAD65、IA-2 或胰岛素自身抗体的出现可预测疾病。在本研究 - Skane 糖尿病预测 (DiPiS) 中，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 遗传因素筛查。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，以确定环境触发因素。特别是，我们将检验以下假设：妊娠不良事件代表胰岛自身免疫的触发因素，胰岛自身免疫将进展为 1 型糖尿病，但仅在某些易感受试者中发生。具体目标是： 1）对瑞典南部地区斯科讷（拥有 120 万居民）的所有新生儿进行筛查； 2) 分析脐带血中 1 型糖尿病高危 HLA 等位基因以及三种胰岛细胞自身抗体 GAD65Ab、IAA 和 IA-2Ab； 3) 分析感染史、妊娠不良事件和心理社会因素作为 1 型糖尿病风险的附加或增强因素，以及妊娠期间的病毒 PCR 和血清学检查； 4) 定义出生时、首次出现自身抗体时和诊断 1 型糖尿病时针对 GAD65、IA-2 和胰岛素的自身抗体的同种型、亚型和表位特异性； 5) 确定自身抗体呈阳性的健康母亲所生新生儿的自身抗原反应性 T 细胞，作为自身免疫暴露的证据；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感染或其他不良事件和心理因素在遗传易感儿童中增加 1 型糖尿病风险的作用。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风险的策略，从而最大限度地降低糖尿病风险。