Epidemiology of Diabetes Complications (EDC) Phase II: renewal

描述（由申请人提供）：与可以预防的2型糖尿病不同，1型糖尿病目前既无法预防也无法治愈，其发病率每年持续上升约3%。因此，对1型糖尿病并发症的持续研究仍然是必要的。糖尿病并发症流行病学（EDC）研究调查了20年来糖尿病并发症的患病率和发病率以及导致糖尿病并发症的危险因素。研究人群是从匹兹堡儿童医院登记处（诊断：1950- 1980）确定的儿童发病1型糖尿病的明确队列。在研究开始时（1986- 1988）参加临床检查的所有658名参与者随后被跟踪长达20年，导致114多篇同行评议出版物。在研究的最后阶段所做的一些惊人的初步观察已经引起了问题和假设，这更新的目的是解决。其中包括各种促糖氧化和抗糖氧化细胞因子和炎症细胞因子之间日益复杂的相互作用，以及并发症快速变化的自然史，这为进一步了解并发症的相互关系和特定风险因素提供了进一步的见解，并使历史数据在医疗保健和保险目的方面过时。因此，目前的应用侧重于进一步评估并发症的发展，总共随访25年，从而对儿童期发病1型糖尿病40年的并发症发展进行合理稳定的估计。这提供了记录发病率风险和估计现代预期寿命的机会，即1965- 1980年诊断出糖尿病的患者，以及自HbA1c检测和自我血糖监测可用以来糖尿病持续时间超过一半的患者。血糖、氧化和炎症应激以及它们引发的宿主反应在并发症发展中的作用将与妇女健康问题一起成为另一个主要焦点，并将继续开展一些合作。最后，我们将使用一种新仪器评估皮肤晚期糖基化终产物及其与并发症风险的关系。为此，将继续进行年度调查，并在25年后进行一次全面检查。公共卫生相关性：该应用的意义在于能够在大型1型糖尿病队列中提供现代HbA1c检测和自我血糖监测时代的发病风险记录和预期寿命估计，而存储标本的可用性为解决应激（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提供了机会。该应用程序还解决了妇女健康问题，并评估了新工具预测并发症风险的能力。由于目前1型糖尿病既无法预防也无法治愈，因此对其并发症的持续研究仍然是必要的，本研究既可以进一步了解并发症的自然史，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further insight into the interrelationships of, and specific risk factors for, complications, and renders historic data outdated for health care and insurance purposes.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.