Biorepository and Coordinating Center for Studies on Cardiovascular Complications of Human Type 1 Diabetes

1型糖尿病(T1D)和2型糖尿病(T2D)的发病机制和自然病史是根本 不同，但这两种疾病会导致许多共同的长期并发症。最值得注意的是心血管疾病 疾病(CVD)是糖尿病患者的主要死亡原因，导致预期寿命缩短。 虽然严格的血糖管理降低了心血管疾病的风险，但绝大多数糖尿病患者 患者无法达到推荐的HbA1c目标。鉴于糖尿病的高患病率(10.5%)和 糖尿病前期(33%)在美国，了解糖尿病相关心血管疾病的发病机制是当务之急 支持制定最佳干预和治疗策略。然而，比较心血管疾病的研究 T1D和T2D的机制严重缺乏。为了解决这个问题，我们建议建立一个心血管系统 存储库-1型糖尿病(CARE-T1D)计划，以促进协作和多模式数据采集 在一个庞大的调查网络中。通过我们领导的6个器官采购和生物制品共享 研究计划，我们有连续15年的操作经验和完善的计划 收集和分发16种不同类型的人体器官移植质量组织的基础设施 捐赠者，包括最近结束的一个肾脏项目和目前的心脏试点计划。我们将利用我们的 与所有57个美国器官采购组织、集中化的全天候呼叫中心和 器官处理和病理核心，以获取、快速处理和储存完整的心血管相关组织 来自60名心血管病患者的供体(心脏、肾脏、血管、血液)，平均分布在三组(T1D， T2D，年龄/性别匹配的非糖尿病对照组)。根据整个器官放射学和钙评分，解剖学 我们将由经验丰富的工作人员系统地进行解剖，以准备各种生物标本 格式(例如，FFPE块、OCT块、闪存冻结)，协议不断发展以支持以下方面的新需求 研究应用。每个病例将接受组织特异性染色，并进行组织病理学检查 委员会认证的病理学家和QA/QC分析。生成的数据将与未识别的数据一起提供 安全的可搜索数据门户中的捐赠者信息和医疗记录，以帮助调查人员选择样本 为他们的研究做准备。我们建议成立一个科学咨询委员会，以评估研究建议和 样本请求，仿照我们现有的组织优先排序委员会。我们将把生物样本分发给 寻求应用多模式方法对样本进行深层表型分析以研究心血管疾病的批准研究人员 T1D与T2D的进展。数据门户还将支持可视化和共享所有外部生成的 数据类型。最后，我们将组织年度会议，促进心血管领域的合作 生物储存库联盟。总而言之，我们预计拟议的CARE-T1D计划将支持发现和 由调查人员合作网络进行的机械性研究，这将增加我们对 糖尿病患者心血管疾病的风险，导致早期发现以及针对T1D和T2D的新的治疗方法。

The pathogenesis and natural history of type 1 diabetes (T1D) and type 2 diabetes (T2D) are fundamentally different, but the two diseases result in many common long-term complications. Most notably, cardiovascular disease (CVD) is the leading cause of death for individuals with diabetes, resulting in a shortened life expectancy. While rigorous blood glucose management reduces the risk for CVD development, the vast majority of diabetes patients are unable to meet recommended HbA1c targets. Given the high prevalence of diabetes (10.5%) and pre-diabetes (33%) in the United States (U.S.), it is imperative to understand diabetes-related CVD pathogenesis to support the development of optimal intervention and treatment strategies. However, studies comparing CVD mechanisms in T1D versus T2D are critically lacking. To address this, we propose to establish a Cardiovascular Repository-Type 1 Diabetes (CARE-T1D) program to facilitate collaboration and multi-modal data acquisition across a large network of investigators. Through our leadership of 6 organ procurement and biospecimen sharing research programs, we have 15 consecutive years of operational experience and well-established programmatic infrastructure for collecting and distributing 16 different types of transplant-quality tissue from human organ donors, including a recently concluded kidney project and current heart pilot program. We will leverage our productive relationships with all 57 U.S. Organ Procurement Organizations, centralized 24/7/365 Call Center and Organ Processing and Pathology Core to procure, to swiftly process and bank a complete CVD-related tissue panel (heart, kidney, vasculature, blood) from 60 donors with CVD, evenly distributed across three groups (T1D, T2D, age/sex-matched no-diabetes controls). Following whole organ radiology and calcium scoring, anatomical dissection will be systematically performed by our highly experienced staff to prepare biospecimens in a variety of formats (e.g., FFPE blocks, OCT blocks, flash-frozen), with protocols evolving to support emerging needs for research applications. Each case will be subjected to tissue-specific stains with histopathologic examination by board certified pathologists and QA/QC analysis. Resulting data will be made available alongside de-identified donor information and medical records in a secure searchable Data Portal to aid investigators in selecting sample sets for their research. We propose to establish a Scientific Advisory Board to evaluate research proposals and sample requests, modeled after our existing Tissue Prioritization Committee. We will distribute biosamples to approved researchers seeking to apply multimodal approaches for deep phenotyping of specimens to study CVD progression in T1D vs T2D. The Data Portal will also support visualization and sharing of all externally generated data types. Finally, we will organize annual meetings to promote collaboration across the Cardiovascular Biorepository Consortium. In sum, we expect the proposed CARE-T1D program will support discovery and mechanistic research, conducted by a collaborative network of investigators, that will increase our understanding of CVD in diabetes, leading to early detection as well as novel treatments specific for both T1D and T2D.