Epidemiology of Diabetes Complications (EDC) Phase II: renewal

描述(申请人提供)：与可以预防的2型糖尿病不同，1型糖尿病目前既不能预防也不能治愈，其发病率继续以每年约3%的速度增长。因此，对1型糖尿病并发症的持续调查仍然势在必行。糖尿病并发症流行病学(EDC)研究对糖尿病并发症的患病率、发病率和危险因素进行了20年的调查。研究人群是匹兹堡儿童医院登记处(诊断：1950-80年)确定的儿童起病1型糖尿病的明确队列。所有658名参与者在研究开始时(1986-88)参加临床考试，随后被跟踪调查长达20年，导致超过114篇同行评议的出版物。在研究的最后阶段提出了一些引人注目的初步意见，提出了这次更新旨在解决的问题和假设。其中包括各种促糖和抗糖氧化和炎性细胞因子之间日益复杂的相互作用，以及迅速变化的并发症的自然历史，这为进一步了解并发症的相互关系和具体的风险因素提供了进一步的了解，并使历史数据对于保健和保险目的来说已经过时。因此，目前的应用侧重于对总随访期为25年的并发症发展的进一步评估，从而使对儿童起病1型糖尿病40年期间并发症发展的合理稳定估计成为可能。这使得有机会记录发病率风险并估计现代的预期寿命，即那些在1965-80年被诊断为糖尿病的人，自有HbA1c检测和自我监测血糖以来，他们的糖尿病病程有一半以上。血糖、氧化和炎症应激的作用，以及宿主对并发症发生的反应，将是与女性健康问题一起的另一个主要关注点，并将继续进行一些合作。最后，我们将使用一种新的仪器评估皮肤晚期糖基化终末产物，以及它们与并发症风险的关系。这将通过继续进行年度调查和在25年的后续行动中进行全面检查来促进。公共卫生相关性：这项应用的意义在于，在大型1型糖尿病队列中，能够在现代糖化血红蛋白检测和自我监测血糖的时代提供发病率风险和预期寿命估计的记录，而储存标本的可用性提供了解决应激(血糖、氧化和/或炎症)及其引发的宿主反应在血管并发症发病机制中的作用的机会。该应用程序还解决了妇女的健康问题，并评估了新工具预测并发症风险的能力。由于目前1型糖尿病既不能预防也不能治愈，对其并发症的持续调查仍然是必要的，目前的研究既可以加深我们对并发症的自然历史的认识，也可以指出预防和管理的新方法。

DESCRIPTION (provided by applicant): Unlike type 2 diabetes, where prevention is possible, type 1 diabetes is currently neither preventable nor curable and its incidence continues to rise approximately 3% per year. Thus, the continuing investigation of type 1 diabetes complications remains imperative. The Epidemiology of Diabetes Complications (EDC) study has examined the prevalence and incidence of and risk factors contributing to the diabetes complications for 20 years. The study population is a well defined cohort of childhood onset type 1 diabetes identified from the Children's Hospital of Pittsburgh Registry (diagnosis: 1950-80). All 658 participants attending a clinical exam at study entry (1986-88) have been subsequently followed for up to 20 years, leading to over 114 peer reviewed publications. A number of striking preliminary observations made during the last phase of the study have given rise to questions and hypotheses this renewal aims to address. These include the increasingly complex interaction between various pro- and anti-glycoxidative and inflammatory cytokines, as well as the rapidly changing natural history of complications which provides further insight into the interrelationships of, and specific risk factors for, complications, and renders historic data outdated for health care and insurance purposes. The current application, therefore, focuses on further assessment of complication development for a total follow up period of 25 years, thus allowing reasonably stable estimates of complication development over 40 years duration of childhood onset type 1 diabetes. This gives the opportunity to document morbidity risk and to estimate life expectancy in the modern era, i.e. for those diagnosed in 1965-80 and who have had more than half their diabetes duration since the availability of HbA1c testing and self monitoring of blood glucose. The roles of glycemic, oxidative and inflammatory stress, and the host's responses they invoke, on complication development will be another major focus along with women's health issues and continuing a number of collaborations. Finally, we will evaluate skin advanced glycosylation end products using a new instrument and how they relate to complication risk. This will be facilitated by continuing the annual surveys and, at 25 years of follow up, a full examination. PUBLIC HEALTH RELEVANCE: The significance of this application lies in the ability to provide, in a large type 1 diabetes cohort, documentation of morbidity risk and estimates of life expectancy in the modern era of HbA1c testing and self monitoring of blood glucose, whereas the availability of stored specimen offers the opportunity to address the role of stress (glycemic, oxidative and/or inflammatory) and the host's response it provokes, in the pathogenesis of vascular complications. This application also addresses women's health issues and evaluates new instruments in their ability to predict complication risk. As currently type 1 diabetes is neither preventable nor curable, the continuing investigation of its complications remains imperative and the present study may both further our knowledge of the natural history of complications and also point to novel approaches to prevention and management.