Environmental Triggers of Type 1 Diabetes

1 型糖尿病的环境诱因

• 批准号: 7071836
• 负责人: OLLI G SIMELL
• 金额: $ 117.08万
• 依托单位: HOSPITAL DISTRICT OF SOUTHWEST FINLAND
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7071836
• 关键词: autoantibody; autoimmunity; child (0-11); clinical research; cooperative study; diabetes mellitus; diagnosis design /evaluation; diagnostic tests; diet; disease /disorder proneness /risk; environment; family genetics; flow cytometry; gene expression; genetic polymorphism; genetic susceptibility; human genetic material tag; human subject; longitudinal human study; microarray technology; polymerase chain reaction; questionnaires; siblings

DESCRIPTION (provided by applicant): To identify environmental triggers of type 1 diabetes (T1D) we have screened genetic T1D risk so far in > 60,000 consecutive newborns at the JDRF Center for Prevention of Type 1 Diabetes in Finland (cities of Turku, Oulu and Tampere; 11,000 annual births) using HLA-DQ gene alleles that associate with risk to or protection from T1D. Those with increased genetic risk and their at-risk siblings are invited to follow-up (3- to 12-month intervals). At this writing, >8,000 high-risk children are in regular follow-up; the oldest children followed from birth are now >7.4 years of age. 474 children have developed ICA, the autoantibody used in the primary screening of follow-up samples, alone (~ 50 % of the children) or in combination with other autoantibodies (~50 %; ICA with IAA, GADA or IA-2A). 64 of the screened children have progressed to T1D; 45 of them were in tight follow-up. If a child becomes ICA positive, all four autoantibodies are measured in child's all collected and future samples, to determine the time of expected onset of the autoimmune attack and to follow disease progression. We collect demographic, medical and life event data. We offer here our huge data and sample banks for collaborative studies. The samples comprise DNA (blood spots) on filter paper and as frozen blood; serum drawn at each follow-up visit; and isolated white blood cells, living white blood cells, RNA from peripheral blood, selected blood cells and other tissues for RNA and other analyses, and stool samples at monthly intervals from children with high genetic risk. The approach is well accepted by the population, as >70% of the at-risk children remain in the follow-up at least for 7 years. The study infrastructure is firm and well-functioning at all three participating Clinical Centers. Large numbers of children represent different stages of T1D development, allowing rapid collection also of new types of samples according to need. Finland's record-high annual TID incidence of 50/100.000 children below the age of 15 years markedly increases cost-efficiency of the case finding. DIPP approach has already proven its value in exploring the role of environmental triggers in T1D development.

描述（由申请人提供）： 为了确定1型糖尿病的环境触发因素（T1D），我们已经在JDRF预防芬兰的1型糖尿病中心（Turku，Oulu和Tampere的城市; 11,000年的年龄出生;使用HLA-DQ Gene Alleles与Alleles cessectiate cestortiate cestortiate cestortiate cestortiate cestoration contery pestractiate conterys筛查了遗传T1D风险，迄今为止连续60,000个新生儿（Turku，Oulu and Tampere; 11,000年龄在Turku，Oulu; tampere; 11,000年生育）中筛选了风险。那些遗传风险增加及其高危兄弟姐妹的人被邀请进行随访（3到12个月的间隔）。在撰写本文中，> 8,000名高风险儿童经常随访；从出生开始的最大的孩子现在> 7.4岁。 474名儿童已经开发了ICA，即单独筛选随访样品（占儿童的50％）或与其他自身抗体（约50％; ICA与IAA，GADA或IA-2A）结合使用的自身抗体。 64个受筛选的孩子已经发展到T1D；其中有45个正在严格的后续行动中。如果孩子成为ICA阳性，则在孩子的所有和未来的样本中测量所有四个自身抗体，以确定自身免疫攻击的预期发作时间并跟随疾病进展。我们收集人口，医疗和生活事件数据。我们在这里提供庞大的数据和样本库进行合作研究。样品包括滤纸上的DNA（血液点）和作为冷冻血液。每次随访时都会吸取血清；以及分离的白细胞，活血细胞，外周血中的R​​NA，选定的血细胞和其他组织进行RNA和其他分析，以及以高遗传风险的儿童的每月间隔进行粪便样品。该方法被人群很好地接受，因为> 70％的处于危险的儿童至少在后续行动中持续了7年。在所有三个参与的临床中心，研究基础设施都是坚定的，功能齐全。大量儿童代表了T1D发展的不同阶段，可以根据需要快速收集新型样本。芬兰创纪录的年度最高年度TID发病率为50/100.000年龄在15岁以下的儿童显着提高了案件发现的成本效益。 DIPP方法已经证明了其在探索环境触发器在T1D开发中的作用方面的价值。