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: 10458684
• 负责人: CHRISTOPHER E FORSMARK
• 金额: $ 19.74万
• 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/10458684
• 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 center; clinical diagnosis; 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.

本佛罗里达大学/降临节健康提案在急性1型糖尿病患者中的目标 胰腺炎联盟（T1 DAPC）将建立一个急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，机制，环境 和生物危险因素，以及随后糖尿病的预测因素。UF糖尿病研究所（UFDI）和 Advent Health Translational Research Institute拥有执行所需的资源和能力 全面的遗传学、免疫学、代谢、组织学和功能测试，以解剖各种 急性胰腺炎后糖尿病的发病机制我们的建议满足了以下四个关键需求： T1 DAPC。1)招募大量急性或急性复发性胰腺炎受试者的平台。的 这两个卫生系统每年收治的急性胰腺炎患者总数接近2 000人。 临床专业知识和现有的临床研究支持结构经验丰富，能力强， 研究所拥有科学专业知识，可以帮助定义和支持各种各样的机械研究， 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（子目的1a）; B）评估受试者的1型 利用定制基因分型阵列和对数加性遗传风险评分的糖尿病遗传风险（子目标1b）; 全面表征急性胰腺炎后的胰腺细胞功能（子目标1c）;以及d）分析 急性胰腺炎的影像学特征可预测随后的糖尿病发展（子目标1d）; 3）A 在发生急性胰腺炎之前研究人类受试者的机会， 内镜逆行胰胆管造影术（ERCP）后。UFHealth和AdventHealth执行 每年约有2,400例此类手术，在其他T1 DAPC中心的参与下， 队列可以在急性胰腺炎发展之前用生物样本和成像数据集合， 为将来的分析提供了非常有用的比较群体。4)收集一个人类胰腺库 来自既往患有胰腺炎的受试者。糖尿病胰腺器官捐赠者网络（NPOD）， 位于UFID，收集和处理来自器官的移植级胰腺和其他组织 采购组织（OPO）在美国各地，并提供给世界各地的调查人员。我们 将利用这一基础设施，沿着与AdventHealth相关的大型本地OPO的基础设施， 有急性胰腺炎病史的人的器官。这将提供一个独特的资源， T1 DAPC，询问组织中糖尿病的机制，这在活体中不易获得。 这可以为T1 DAPC机制研究提供临床病理相关性。我们认为， 所提出的分析对于T1 DAPC的工作是必要的，我们能够完全支持这些目标 或由T1 DAPC选择的相关目标。