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: 10463660
• 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/10463660
• 关键词: Acute; Address; Adult; American; Antibodies; Antigens; Area; Autoantibodies; Autoantigens; Autoimmunity; Beta Cell; Biological Markers; Cell physiology; Characteristics; Clinical; Clinical Research; Collaborations; Complication; Data; Data Store; 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; OGTT; Observational Study; Pancreas; Pancreatic Diseases; Pancreatitis; Participant; Patients; Phosphoric Monoester Hydrolases; Prediabetes syndrome; Proteins; Recovery; Recurrence; Relative Risks; Research; Research Infrastructure; Resolution; Resources; Risk; Sampling; Schedule; Serum; Severities; Solid; Testing; Time; Translational Research; Universities; Visit; Work; acute pancreatitis; base; chronic pancreatitis; clinical center; clinical infrastructure; cohort; data exchange; data management; design; diabetes pathogenesis; diabetic patient; experience; faculty research; follow-up; insulin sensitivity; member; non-diabetic; organizational structure; personalized medicine; predictive marker; prevent; programs; prospective; recruit; 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.

摘要。 UPMC急性胰腺炎后糖尿病研究临床中心（UPMC CC），一个多学科的 匹兹堡大学和UPMC的一个研究项目，寻求成为1型的创始成员。 糖尿病急性胰腺炎联盟（T1 DAPC）。UPMC CC的组织结构允许 胰腺疾病患者的流行病学、临床和 翻译视角它的优势包括优秀的教师，他们在所有相关领域拥有丰富的专业知识， T1 DAPC，高患者量，进行高质量临床和转化研究的基础设施，以及 在多中心研究中具有强大和成功的合作、领导和贡献的跟踪记录， 财团完善、高效和有效的临床和研究基础设施，促进患者增加， 样品处理、数据管理和传输以及分析将支持该方案。建议的研究 在本申请中，将直接解决T1 DAPC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）由于先前未被认识到的 在AP发作消退后，β细胞功能持续丧失。我们将确定PAP-DM AP后的β细胞功能和胰岛素敏感性的自然史，以及AP后β细胞功能和胰岛素敏感性的贡献。 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： 1)确定与PAP-DM相关的风险和特征。我们将招募并前瞻性地遵循 向上的非糖尿病患者从AP中恢复，并比较PAP-DM与对照组的发病率。目标2） 确定AP消退后β细胞功能变化的自然史。使用Aim的队列 1（AP和对照），该目标将确定第一年内是否发生临床上无症状的持续β细胞丢失 在AP消退后，以及它是否与PAP-DM的发作相关。此外，这一目标将决定 β细胞丢失是否伴随着胰岛素敏感性的变化，以及β细胞丢失是否与胰岛素敏感性的变化相关。 自身免疫和胰腺外分泌炎症的生物标志物。目标3）量化beta的贡献 CP患者对DM的细胞自身免疫其他NIDDK的现有数据和储存的血清样本- 将使用申办的队列（NAPS 2，PROCEED）测量CP患者的β细胞自身抗体， 并与非糖尿病患者和非糖尿病健康对照组进行比较。拟议的研究将 提供关键信息，以设计个性化的医疗方法，以预防和治疗PAP-DM的基础上， 病理生理学本研究为PAP-DM的进一步研究奠定了基础。为了确保其成功， 有效性，T1 DAPC可以依靠世界一流的教师，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。