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

人类1型糖尿病心血管并发症研究生物储存库和协调中心

• 批准号: 10879240
• 负责人: MARK A. ATKINSON
• 金额: $ 16.32万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10879240
• 关键词: Address; Age; Anatomy; Blood; Blood Glucose; Board Certification; Calcium; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Collaborations; Collection; Data; Databases; Development; Diabetes Mellitus; Disease; Disease Progression; Dissection; Early Diagnosis; Freezing; Glycosylated hemoglobin A; Heart; High Prevalence; Human; Individual; Infrastructure; Insulin-Dependent Diabetes Mellitus; Intervention; Kidney; Leadership; Life Expectancy; Medical Records; Modeling; Molecular; Natural History; Non-Insulin-Dependent Diabetes Mellitus; Organ; Organ Donor; Organ Procurements; Pathogenesis; Pathologist; Pathology; Patients; Performance; Phase; Phenotype; Policies; Prediabetes syndrome; Process; Productivity; Protocols documentation; Qualifying; Quality Control; Radiology Specialty; Recommendation; Research; Research Personnel; Research Proposals; Risk Reduction; Sampling; Secure; Specimen; Stains; Technology; Tissue Sample; Tissues; Transplantation; United States; United States National Institutes of Health; Visualization; biobank; cardiovascular disorder risk; data acquisition; data portal; data sharing; diabetes control; experience; histopathological examination; human tissue; meetings; multimodal data; multimodality; novel; programs; public repository; racial diversity; repository; sex; tissue resource; treatment strategy; type I and type II diabetes

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.

1型糖尿病（T1D）和2型糖尿病（T2D）的发病机理和自然病史从根本上是 不同，但两种疾病导致许多常见的长期并发症。最值得注意的是心血管 疾病（CVD）是糖尿病患者死亡的主要原因，导致预期寿命缩短。 严格的血糖管理降低了CVD发展的风险，但绝大多数糖尿病 患者无法满足建议的HBA1C靶标。鉴于糖尿病患病率很高（10.5％）和 在美国（美国）糖尿病前糖尿病（33％），必须了解与糖尿病相关的CVD发病机理 支持最佳干预和治疗策略的发展。但是，比较CVD的研究 T1D与T2D的机制严重缺乏。为了解决这个问题，我们建议建立心血管 存储库型1糖尿病（CARE-T1D）计划，以促进协作和多模式数据获取 在大型调查人员网络中。通过我们对6个器官采购和生物仿生共享的领导 研究计划，我们连续15年的运营经验和完善的程序化 从人体器官那里收集和分发16种不同类型的移植质量组织的基础设施 捐助者，包括最近结束的肾脏项目和当前的心脏试验计划。我们将利用我们的 与所有57个美国器官采购组织的生产关系，集中式24/7/365呼叫中心和 器官加工和病理核心要采购，迅速处理和库存完整的CVD相关组织 来自60个带有CVD的捐赠者的面板（心脏，肾脏，脉管系统，血液，血液），均匀分布在三组中（T1D，T1D， T2D，年龄/性别匹配的无糖尿病控制）。遵循整个器官放射学和钙评分，解剖学 我们经验丰富的员工将系统地进行解剖，以准备多种多样 格式（例如，FFPE块，OCT块，闪光灯）的格式，协议不断发展以支持新兴需求 研究应用。每种情况都将通过组织特异性污渍进行组织病理学检查 董事会认证的病理学家和QA/QC分析。结果数据将与De-SIDAIFED一起提供 捐助者信息和医疗记录在可搜索的可搜索数据门户中，以帮助调查人员选择样本 为他们的研究设定。我们建议建立一个科学顾问委员会，以评估研究建议和 样本请求，以我们现有的组织优先委员会为基础。我们将将生物样本分配给 批准的研究人员寻求采用多模式方法进行标本的深层表型来研究CVD T1D与T2D的进展。数据门户还将支持所有外部生成的可视化和共享 数据类型。最后，我们将组织年度会议，以促进心血管的合作 生物座席联盟。总而言之，我们预计拟议的Care-T1D计划将支持发现和 由调查人员的协作网络进行的机械研究将增加我们的理解 CVD的糖尿病，导致早期检测以及针对T1D和T2D的新型治疗方法。