Type 1 Diabetes in Acute Pancreatitis Consortium - Clinical Centers

急性胰腺炎联盟中的 1 型糖尿病 - 临床中心

• 批准号: 10264900
• 负责人: CHRISTOPHER E FORSMARK
• 金额: $ 19.85万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-16 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10264900
• 关键词: Acute; Address; Alpha Cell; Area; Arginine; Autoantibodies; Autoimmune; Bayesian Analysis; Beta Cell; Biological; Biological Markers; Blood; Blood specimen; Cell physiology; Cells; Clinical; Clinical Research; Collection; Coupled; Custom; DNA; Data; Development; Diabetes Mellitus; Early Diagnosis; Endoscopic Retrograde Cholangiopancreatography; Enrollment; Etiology; Fatty acid glycerol esters; Feces; Fibrosis; Florida; Functional disorder; Future; Genetic; Genetic Risk; Genotype; Glucose tolerance test; Health; Health system; Histologic; Human; Image; Immune; Immunohistochemistry; Immunologics; Incidence; Individual; Inflammatory; Infrastructure; Institutes; Insulin; Insulin Resistance; Insulin deficiency; Insulin-Dependent Diabetes Mellitus; Islet Cell; Laboratories; Location; Magnetic Resonance Imaging; Measures; Metabolic; Morphology; Necrosis; OGTT; Organ; Organ Donor; Organ Procurements; Pancreas; Pancreatic Diseases; Pancreatic Polypeptide; Pancreatic duct; Pancreatitis; Pathogenesis; Patients; Phenotype; Population; Prevalence; Prevention; Procedures; Process; Prospective cohort; Public Health; Radioimmunoassay; Recording of previous events; Relapse; Research Institute; Research Personnel; Research Support; Resources; Risk; Risk Factors; Saliva; Sampling; Staging; Statistical Data Interpretation; Structure; System; Testing; Tissue Sample; Tissue and Organ Procurement; Tissues; Translational Research; Transplantation; United States; Universities; Urine; Visit; Work; acute pancreatitis; biobank; clinical Diagnosis; clinical center; cohort; diabetes mellitus therapy; diabetes pathogenesis; diabetes risk; effective therapy; endocrine pancreas development; experience; follow-up; high risk; human subject; indexing; insulin secretion; insulitis; internal control; islet; islet autoimmunity; novel marker; pancreas imaging; pancreatic juice; participant enrollment; programs; prospective; recruit; regeneration potential; risk stratification; saliva sample

The objective of this University of Florida/Advent Health proposal within the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) is to establish a longitudinal prospective cohort of patients with acute and acute relapsing pancreatitis in order to investigate the incidence, pathophysiology, mechanisms, environmental and biologic risk factors, and predictors of subsequent diabetes. The Diabetes Institute at UF (UFDI) and the Advent Health Translational Research Institute have the resources and capabilities required to perform comprehensive genetic, immunologic, metabolic, histologic, and functional testing to dissect the various mechanisms underlying diabetes following acute pancreatitis. Our proposal addresses four key needs of the T1DAPC. 1) A platform for recruiting large numbers of subjects with acute or acute relapsing pancreatitis. The combined volumes of both health systems approach 2,000 patients admitted with acute pancreatitis yearly. The clinical expertise and existing clinical research support structure is experienced and capable, and the two Institutes have the scientific expertise to help define and support the whole variety of mechanistic studies that will be undertaken; 2) Mechanistic studies of diabetes after acute pancreatitis including a) measuring autoantibody markers of islet autoimmunity after acute pancreatitis (subaim 1a); b) assessing subjects’ type 1 diabetes genetic risk leveraging a custom genotyping array and log additive genetic risk score (subaim 1b); comprehensively characterizing 𝛽𝛽-cell function after acute pancreatitis (subaim 1c); and d) analyzing the imaging features of acute pancreatitis which predict the subsequent development of diabetes (subaim 1d); 3) A consortium opportunity to study human subjects prior to the development of acute pancreatitis, that occurring after endoscopic retrograde cholangiopancreatography (ERCP). UFHealth and AdventHealth perform approximately 2,400 of these procedures yearly, and with the participation of other T1DAPC centers, a sub- cohort could be assembled with biospecimens and imaging data prior to the development of acute pancreatitis, providing a very useful comparison population for future analyses. 4) Collecting a bank of human pancreata from subjects with previous pancreatitis. The Network for Pancreatic Organ donors with Diabetes (nPOD), housed at the UFID, collects and processes transplant-grade pancreata and other tissues from organ procurement organizations (OPOs) across the U.S. and provides them for investigators around the world. We will leverage this infrastructure, along with that of a large local OPO associated with AdventHealth, to obtain organs from individuals with a history of acute pancreatitis. This will provide a unique resource for the T1DAPC, to interrogate the mechanisms of diabetes in tissue, which is not readily accessible in living subjects. This can provide a clinicopathologic correlation for the T1DAPC mechanistic studies. We believe the types of analyses proposed will be necessary for the work of the T1DAPC, and we are able to fully support these aims or related aims selected by the T1DAPC.

这项佛罗里达大学/Advent健康提案的目标是急性1型糖尿病患者 胰腺炎联盟(T1DAPC)旨在建立一个急性和慢性胰腺炎患者的纵向前瞻性队列。 急性复发性胰腺炎的发病率、病理生理学、发病机制、环境 和生物风险因素，以及后续糖尿病的预测因素。UF糖尿病研究所(UFDI)和 Coment Health Translative Research Institute拥有所需的资源和能力 全面的遗传、免疫学、代谢、组织学和功能测试，以剖析各种 急性胰腺炎后糖尿病的发病机制。我们的建议解决了四个关键需求 T1DAPC。1)招募大量急性或急性复发性胰腺炎患者的平台。这个 这两个医疗系统的合计数量每年接近2000名急性胰腺炎患者。 临床专业知识和现有的临床研究支持结构是经验丰富和有能力的，两者 研究所拥有科学专业知识来帮助定义和支持各种机械研究， 2)急性胰腺炎后糖尿病的机制研究，包括a)测量 急性胰腺炎后胰岛自身免疫的自身抗体标记物(亚目标1a)；b)评估受试者的1型 利用定制基因分型阵列和记录相加遗传风险分数的糖尿病遗传风险(次级目标1b)； 全面表征急性胰腺炎后的𝛽𝛽细胞功能(亚目的1c)；和d)分析 预测糖尿病后续发展的急性胰腺炎的影像特征(亚目标1D)；3)A 联盟有机会在急性胰腺炎发生之前研究人类受试者 经内窥镜逆行胰胆管造影术(ERCP)后。UFHealth和AdventHealth表现出色 每年大约有2400个这样的程序，并在其他T1DAPC中心的参与下， 队列可以在急性胰腺炎发生之前与生物标本和成像数据组合在一起， 为将来的分析提供了一个非常有用的比较总体。4)收集一批人胰腺 来自有过胰腺炎病史的受试者。糖尿病患者胰腺器官捐献网络(NPOD) 在UFID，收集和处理器官中移植级的胰腺和其他组织 美国各地的采购组织(OPO)，并为世界各地的调查人员提供这些组织。我们 将利用此基础设施，以及与AdventHealth关联的大型本地OPO，以获得 来自有急性胰腺炎病史的个人的器官。这将为 T1DAPC，以询问组织中糖尿病的机制，这在活体受试者中是不容易获得的。 这可为T1DAPC的发病机制研究提供临床病理依据。我们相信这些类型的 建议的分析对于T1DAPC的工作是必要的，我们能够完全支持这些目标 或由T1DAPC选择的相关目标。