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

1型糖尿病（T1 D）和2型糖尿病（T2 D）的发病机制和自然史基本上是 这两种疾病有所不同，但会导致许多常见的长期并发症。最明显的是， 心血管疾病（CVD）是糖尿病患者死亡的主要原因，导致预期寿命缩短。 虽然严格的血糖管理降低了CVD发展的风险，但绝大多数糖尿病患者 患者无法达到推荐的HbA 1c目标。鉴于糖尿病患病率高（10.5%）， 糖尿病前期（33%）在美国（美国），了解糖尿病相关的CVD发病机制是非常必要的， 支持制定最佳干预和治疗策略。然而，比较CVD的研究 与T2 D相比，T1 D中的机制严重缺乏。为了解决这个问题，我们建议建立一个心血管 数据库-1型糖尿病（CARE-T1 D）计划，以促进协作和多模式数据采集 一个庞大的调查网络通过我们领导的6个器官采购和生物标本共享 研究计划，我们有连续15年的运营经验和完善的方案 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，包括最近结束的肾脏项目和目前的心脏试点计划。我们将利用我们 与所有57个美国器官采购组织建立了富有成效的关系，集中了24/7/365呼叫中心， 器官处理和病理学核心，用于采购、快速处理和储存完整的CVD相关组织 来自60名患有CVD的供体的面板（心脏、肾脏、脉管系统、血液），均匀分布在三组（T1 D， T2 D，年龄/性别匹配的无糖尿病对照）。在全器官放射学和钙评分后，解剖学 解剖将由我们经验丰富的工作人员系统地进行，以制备各种生物标本。 格式（例如，FFPE组织块、OCT组织块、快速冷冻），协议不断发展，以支持以下新需求： 研究应用。每例病例将接受组织特异性染色和组织病理学检查， 委员会认证的病理学家和QA/QC分析。所产生的数据将与去识别的 在一个安全的可搜索数据门户中提供供体信息和医疗记录，以帮助研究者选择样本 为他们的研究做准备。我们建议成立一个科学顾问委员会，负责评估研究建议， 样本请求，仿照我们现有的组织优先级委员会。我们会把生物样本分发给 经批准的研究人员寻求应用多模式方法对标本进行深度表型分析，以研究CVD T1 D vs T2 D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，以促进心血管领域的合作。 生物储藏库联盟。总之，我们预计拟议的CARE-T1 D计划将支持发现和 由研究人员协作网络进行的机械研究，这将增加我们的理解 这一发现有助于早期发现以及针对T1 D和T2 D的新型治疗。

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.