UPMC Clinical Center for the Study of Diabetes After Acute Pancreatitis

UPMC 急性胰腺炎后糖尿病研究临床中心

• 批准号: 10673184
• 负责人: Frederico G. S. Toledo
• 金额: $ 27.81万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-17 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673184
• 关键词: Acceleration; Acute; Address; Adult; American; Antibodies; Antigens; Area; Autoantibodies; Autoantigens; Autoimmunity; Beta Cell; Biological Markers; Cell physiology; Characteristics; Clinical; Clinical Research; Collaborations; Complication; Data; Diabetes Mellitus; Disease; Effectiveness; Endocrine; Enrollment; Ensure; Epidemiology; Etiology; Evaluation; Exocrine pancreas; Faculty; Foundations; Functional disorder; Funding; Hospitals; Incidence; Individual; Inflammation; Infrastructure; Injury; Insulin; Insulin-Dependent Diabetes Mellitus; Interdisciplinary Study; Knowledge; Leadership; Measures; Metabolic; Monophenol Monooxygenase; Multicenter Studies; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Nursing Faculty; OGTT; Observational Study; Pancreas; Pancreatic Diseases; Pancreatitis; Participant; Patients; Phosphoric Monoester Hydrolases; Prediabetes syndrome; Predisposition; Proteins; Random Allocation; Recovery; Recurrence; Relative Risks; Research; Research Infrastructure; Resolution; Resources; Risk; Sampling; Schedule; Serum; Severities; Solid; Testing; Time; Translational Research; Universities; Visit; Work; acute pancreatitis; chronic pancreatitis; clinical center; clinical infrastructure; cohort; data exchange; data management; design; diabetes pathogenesis; diabetic patient; experience; follow-up; insulin sensitivity; member; non-diabetic; organizational structure; personalized medicine; predictive marker; prevent; programs; prospective; recruit; research faculty; secondary endpoint; stem; success; translational study; zinc-binding protein

ABSTRACT. The UPMC Clinical Center for the Study of Diabetes after Acute Pancreatitis (UPMC CC), a multidisciplinary research program at the University of Pittsburgh and UPMC, seeks to be a founding member of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC). UPMC CC’s organizational structure allows comprehensive characterization of patients with pancreatic disorders from an epidemiological, clinical and translational perspective. Its strengths include outstanding faculty with vast expertise in all areas relevant to the T1DAPC, high patient volumes, infrastructure to conduct high-quality clinical and translational studies, and a track record of strong and successful collaborations, leadership and contributions to multicenter studies and consortiums. The well-established, efficient and effective clinical and research infrastructure for patient accrual, sample processing, data management and transfer, and analysis will support the program. The studies proposed in this application will directly address the overriding objective of the T1DAPC. These explore a new concept that post-acute pancreatitis diabetes mellitus AP (PAP-DM) occurs rapidly because of previously unrecognized ongoing loss of beta cells function after the AP episode is resolved. We will determine how rapidly PAP-DM develops after AP, the natural history of beta-cell function and insulin sensitivity after AP, and the contribution of beta cell autoimmunity to the pathogenesis of DM after AP and chronic pancreatitis (CP). Specific aims: Aim 1) Determine the risk of and characteristics associated with PAP-DM. We will recruit and prospectively follow up non-diabetic patients who recover from AP and compare the incidence of PAP-DM to controls. Aim 2) Determine the natural history of changes in beta cell function after resolution of AP. Using the cohorts of Aim 1 (AP and controls), this aim will determine if clinically silent, ongoing beta cell loss occurs during the first year after AP resolution and whether it correlates with the onset of PAP-DM. Additionally, this aim will determine whether beta cell loss is accompanied by changes in insulin sensitivity and whether it correlates with beta-cell autoimmunity and biomarkers of exocrine pancreas inflammation. Aim 3) Quantify the contribution of beta cell autoimmunity to DM in patients with CP. Existing data and stored serum samples from other NIDDK- sponsored cohorts (NAPS2, PROCEED) will be used to measure beta cell autoantibodies in patients with CP who have DM and compare with patients without DM and non-diabetic healthy controls. The proposed studies will provide crucial information to design personalized-medicine approaches to prevent and treat PAP-DM based on pathophysiology. The studies will lay the groundwork for future research on PAP-DM. To ensure its success and effectiveness, the T1DAPC can count on the solid foundation of world-class faculty, extensive clinical resources, high patient volumes, clinical and translational research experience, ability to work with multiple centers as either leaders or participants in pancreatic research, and record of accomplishments.

抽象的。 UPMC 急性胰腺炎后糖尿病研究临床中心 (UPMC CC) 匹兹堡大学和 UPMC 的研究项目，寻求成为 Type 1 的创始成员 急性胰腺炎联盟 (T1DAPC) 中的糖尿病。 UPMC CC 的组织结构允许 从流行病学、临床和临床方面全面描述胰腺疾病患者的特征 翻译视角。其优势包括优秀的师资队伍，在与大学相关的所有领域拥有丰富的专业知识。 T1DAPC、大量患者、进行高质量临床和转化研究的基础设施以及 强有力和成功的合作、领导力和对多中心研究的贡献的记录 财团。完善、高效、有效的临床和研究基础设施，用于患者累积， 样品处理、数据管理和传输以及分析将为该计划提供支持。提出的研究 该应用程序将直接解决 T1DAPC 的首要目标。这些探索了一个新概念 急性胰腺炎后糖尿病 AP (PAP-DM) 由于之前未被识别而迅速发生 AP 发作解决后，β 细胞功能持续丧失。我们将确定 PAP-DM 的速度有多快 AP 后的发展、AP 后 β 细胞功能和胰岛素敏感性的自然史以及贡献 β细胞自身免疫对 AP 和慢性胰腺炎 (CP) 后 DM 发病机制的影响。具体目标：目标 1) 确定 PAP-DM 的风险和相关特征。我们将招募并前瞻性地关注 研究从 AP 中恢复的非糖尿病患者，并将 PAP-DM 的发生率与对照组进行比较。目标2) 确定 AP 消退后 β 细胞功能变化的自然史。使用 Aim 群组 1（AP 和对照），该目标将确定第一年是否发生临床无症状、持续的 β 细胞损失 AP 解决后以及它是否与 PAP-DM 的发生相关。此外，这个目标将决定 β细胞损失是否伴随着胰岛素敏感性的变化以及它是否与β细胞相关 自身免疫和外分泌胰腺炎症的生物标志物。目标 3）量化 beta 的贡献 CP 患者对 DM 的细胞自身免疫。来自其他 NIDDK 的现有数据和存储的血清样本 赞助队列（NAPS2、PROCEED）将用于测量 CP 患者的 β 细胞自身抗体，这些患者 患有糖尿病并与没有糖尿病的患者和非糖尿病健康对照进行比较。拟议的研究将 为设计个性化医疗方法来预防和治疗 PAP-DM 提供重要信息 病理生理学。这些研究将为未来 PAP-DM 的研究奠定基础。为确保其成功并 T1DAPC 拥有世界一流的师资力量、广泛的临床资源、 大量患者、临床和转化研究经验、与多个中心合作的能力 胰腺研究的领导者或参与者，以及成就记录。