Southern California Clinical Center of the Type 1 Diabetes in Acute Pancreatitis Consortium

南加州 1 型糖尿病急性胰腺炎联盟临床中心

• 批准号: 10264920
• 负责人: Mark Goodarzi
• 金额: $ 31.1万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 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/10264920
• 关键词: Address; Artificial Intelligence; Autoantibodies; Autoimmune; Biological Assay; Blood; California; Clinical; Collection; County; Data; Data Set; Defect; Development; Diabetes Mellitus; Endocrinology; Enrollment; Epidemiology; Etiology; Fasting; Frequencies; Future; Gastroenterology; Genetic; Genetic Risk; Genotype; Glucose; Goals; Health; Homeostasis; Hormonal; Hospitalization; Hospitals; Image; Incidence; Individual; Insulin; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Intake; Lead; Light; Liquid substance; Los Angeles; MRI Scans; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Meta-Analysis; Metabolic; Methods; Modeling; Necrosis; Non-Insulin-Dependent Diabetes Mellitus; Pancreas; Pancreatitis; Participant; Patients; Phenotype; Physiological; Physiology; Preventive; Proteins; Proteomics; Protocols documentation; Public Health; Recurrence; Research; Research Personnel; Risk; Risk Factors; Sampling; Scanning; Set protein; Severities; Signal Transduction; Swelling; Testing; Therapeutic; United States; X-Ray Computed Tomography; acute pancreatitis; base; chronic pancreatitis; clinical center; cohort; design; diabetes risk; ethnic diversity; experience; genetic association; genome wide association study; genome-wide; high risk; imaging biomarker; improved; innovation; insulin secretion; intravenous glucose tolerance test; islet; islet autoimmunity; islet cell antibody; non-diabetic; novel; novel strategies; pancreas imaging; predictive marker; predictive modeling; prevent; prospective; recruit; response; type I and type II diabetes

This application describes a robust Southern California-based Clinical Center for participation in the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC). Proposed protocols address the metabolic mechanisms and the genetic, protein, and imaging signature of patients with acute pancreatitis (AP) and recurrent acute pancreatitis (RAP) who are at high risk for future development of diabetes. AP is the most common cause of pancreatogenic diabetes. While meta-analyses have revealed an incidence rate of 23% for diabetes arising after AP, they have not shed light on the type of diabetes that develops, which may comprise autoimmune or idiopathic type 1 diabetes (T1DM), type 2 diabetes (T2DM), or a unique diabetes pathobiology. A detailed understanding of diabetes developing after AP will yield great benefit by facilitating novel approaches to predict, prevent, and treat this form of diabetes. The following aims are proposed to address these goals: Specific Aim 1. Recruit a cohort of non-diabetic patients with a recent episode of AP or RAP and prospectively characterize their islet autoimmunity and glucose/insulin homeostasis using the frequently sampled intravenous glucose tolerance test and mixed meal tolerance tests performed 1 month after hospital discharge, and at 3, 6, 12, 18, and 24 months, and yearly thereafter. The goals of this aim are to (a) determine the incidence of diabetes after AP, (b) identify the types of diabetes that develop after AP, (c) identify early metabolic trajectories associated with post-AP diabetes, (d) assemble the cohort that will be the platform for Aims 2-4. Specific Aim 2. Evaluate genetic and protein risk factors for diabetes in patients with AP or RAP. This Aim will evaluate association of genetic risk scores for T1DM and T2DM with post AP diabetes. Thirteen candidate proteins, associated with post AP diabetes in preliminary studies, will be assessed for association with incident diabetes after AP, yielding a key set of proteins with utility not only in diabetes prediction but also targets for future preventive or therapeutic measures. Specific Aim 3. Characterize the imaging phenotype that predicts development of diabetes after AP or RAP. Retrospective CT scans obtained during hospitalization for AP as well as CT and novel multiparametric MRI scans obtained 1 and 12 months afterward will undergo artificial intelligence analysis to identify the imaging biomarkers that signal diabetes risk. Specific Aim 4. Develop a multi-factorial model to predict development of diabetes after AP or RAP. A wealth of data will be collected from Aims 1-3, which will be combined with clinical factors to build and validate (in independent datasets) an integrative predictive model of post AP diabetes. The goal is to create a model that can be used in clinical settings to identify those at highest risk, facilitating targeted measures to prevent diabetes. This innovative research will be conducted by an experienced team of investigators in endocrinology, gastroenterology, imaging, physiology, and epidemiology to solve a problem of great public health significance.

该申请描述了一个强大的总部位于南加州的临床中心，以参与1型 急性胰腺炎联盟（T1DAPC）中的糖尿病。提出的方案解决了代谢机制 以及急性胰腺炎（AP）和复发性急性患者的遗传，蛋白质和成像特征 胰腺炎（RAP）有糖尿病未来发育的高风险。 AP是最常见的原因 胰腺生成糖尿病。尽管荟萃分析显示糖尿病的发病率为23％ AP，他们还没有阐明发展的糖尿病类型，可能包括自身免疫性或特发性 1型糖尿病（T1DM），2型糖尿病（T2DM）或独特的糖尿病病理生物学。详细的理解 通过促进预测，预防和 治疗这种形式的糖尿病。提出了以下目的来解决这些目标： 具体目标1。招募最近的AP或RAP发作的非糖尿病患者的队列，并前瞻性地招募 使用经常静脉注射的胰岛自身免疫性和葡萄糖/胰岛素稳态表征 出院后1个月进行葡萄糖耐受性测试和混合饮食测试，在3、6， 12、18和24个月，此后每年。该目标的目标是（a）确定糖尿病的发生 AP之后，（b）识别AP后发生的糖尿病类型，（c）识别早期代谢轨迹 与后AP糖尿病相关，（d）组装将成为目标2-4的平台。 特定目的2。评估AP或RAP患者糖尿病的遗传和蛋白质危险因素。这个目标 将评估T1DM和T2DM与AP糖尿病的遗传风险评分的关联。十三位候选人 将评估与初步研究中AP后糖尿病有关的蛋白质，以评估与事件相关的蛋白质 AP之后的糖尿病，产生一组蛋白质的蛋白质，不仅在糖尿病预测中，还针对目标 未来的预防或治疗措施。 特定目的3。表征预测AP或RAP后糖尿病发展的成像表型。 在住院期间获得的回顾性CT扫描以及CT和新型多参数MRI 1和12个月后获得的扫描将进行人工智能分析以识别成像 信号糖尿病风险的生物标志物。 特定目标4。开发一个多因素模型，以预测AP或RAP后糖尿病的发展。财富 数据将从AIMS 1-3收集，该目标将与临床因素结合起来，以构建和验证（在 独立数据集）AP后糖尿病的综合预测模型。目标是创建一个模型 可以在临床环境中使用，以识别那些处于最高风险的情况，从而促进了针对性措施以预防糖尿病。 这项创新的研究将由经验丰富的内分泌研究人员团队进行， 胃肠病学，成像，生理学和流行病学，以解决具有巨大公共健康意义的问题。