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: 10512888
• 负责人: MARK A. ATKINSON
• 金额: $ 157.9万
• 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/10512888
• 关键词: Address; Age; Anatomy; Animal Model; Aorta; Atlases; Attention; Award; Big Data; Blood; Blood Glucose; Blood Vessels; Cadaver; Calcium; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cells; Cerebrovascular Disorders; Collaborations; Collection; Complication; Coronary artery; Coronary heart disease; Data; Data Set; Databases; Deposition; Development; Diabetes Mellitus; Diabetic Nephropathy; Diagnosis; Disease; Disease Progression; Dissection; Drug or chemical Tissue Distribution; Early Diagnosis; Evaluation; FAIR principles; Freezing; Glycosylated hemoglobin A; Goals; Heart; High Prevalence; Human; Human BioMolecular Atlas Program; Hypertension; Image; Immune; Individual; Infrastructure; Institution; Insulin-Dependent Diabetes Mellitus; International; Intervention; Kidney; Knowledge; Lead; Leadership; Life; Life Expectancy; Link; Longevity; Medical Records; Metadata; Modeling; Molecular; Mononuclear; Morbidity - disease rate; Myocardium; Natural History; Neonatal; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Organ Donor; Organ Procurements; Overweight; Pancreas; Pathogenesis; Pathogenicity; Pathologist; Pathology; Patients; Performance; Peripheral; Peripheral arterial disease; Persons; Phase; Phenotype; Plasma; Policies; Prediabetes syndrome; Prevention; Procedures; Process; Protocols documentation; Quality Control; Radiology Specialty; Recommendation; Research; Research Personnel; Research Project Grants; Research Proposals; Risk Factors; Sampling; Scanning; Secure; Serum; Severity of illness; Specimen; Stains; Standardization; Sum; Technology; Tissue Sample; Tissues; To specify; Transplantation; United States; United States National Institutes of Health; Visualization; autonomic neuropathy; base; biobank; biomarker discovery; cardiovascular disorder risk; central database; cohort; data acquisition; data portal; data sharing; diabetes control; diabetes risk; diabetic; diabetic cardiomyopathy; digital pathology; experience; glycemic control; histopathological examination; human tissue; meetings; mortality; multimodal data; multimodality; novel; novel therapeutic intervention; prevent; 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) 的发病机制和自然史从根本上来说是不同的。 不同，但这两种疾病会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。 虽然严格的血糖管理可以降低发生 CVD 的风险，但绝大多数糖尿病患者 患者无法达到建议的 HbA1c 目标。鉴于糖尿病患病率很高（10.5%） 在美国 (U.S.) 糖尿病前期 (33%)，了解糖尿病相关的 CVD 发病机制势在必行 支持制定最佳干预和治疗策略。然而，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 1 型糖尿病存储库 (CARE-T1D) 计划促进协作和多模式数据采集 跨越庞大的调查员网络。通过我们领导的 6 个器官获取和生物样本共享 研究方案，我们拥有连续15年的运营经验和完善的方案 用于收集和分发 16 种不同类型的人体器官移植质量组织的基础设施 捐助者，包括最近结束的肾脏项目和当前的心脏试点计划。我们将利用我们的 与所有 57 个美国器官采购组织建立了富有成效的关系，集中式 24/7/365 呼叫中心和 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 一组（心脏、肾脏、脉管系统、血液）来自 60 名患有 CVD 的捐献者，均匀分布在三组（T1D、 T2D，年龄/性别匹配的非糖尿病对照）。继全器官放射学和钙评分、解剖学 我们经验丰富的工作人员将系统地进行解剖，以制备各种生物样本 格式（例如 FFPE 块、OCT 块、闪冻），协议不断发展以支持新兴需求 研究应用。每个病例都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。结果数据将与去识别化的数据一起提供 捐赠者信息和医疗记录保存在安全的可搜索数据门户中，以帮助研究人员选择样本 为他们的研究设置。我们建议成立一个科学顾问委员会来评估研究提案和 样本请求，以我们现有的组织优先委员会为蓝本。我们将把生物样本分发给 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，以促进心血管领域的合作 生物样本库联盟。总之，我们预计拟议的 CARE-T1D 计划将支持发现和 由研究人员协作网络进行的机制研究，这将增加我们的理解 糖尿病中的心血管疾病，从而实现早期检测以及针对 T1D 和 T2D 的新治疗方法。