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

本申请描述了一个强大的南加州的临床中心参与1型 糖尿病急性胰腺炎联盟（T1 DAPC）。拟议的协议解决代谢机制 以及急性胰腺炎（AP）和复发性急性胰腺炎（AP）患者的遗传、蛋白质和影像学特征。 胰腺炎（RAP），他们是未来发展糖尿病的高风险人群。AP是最常见的原因 胰源性糖尿病虽然荟萃分析显示，糖尿病的发病率为23%， AP，他们没有阐明糖尿病的类型，可能包括自身免疫性或特发性 1型糖尿病（T1 DM）、2型糖尿病（T2 DM）或独特的糖尿病病理学。详细了解 AP后糖尿病的发展将产生巨大的好处，促进新的方法来预测，预防， 治疗这种形式的糖尿病。为实现这些目标，提出了以下目标： 具体目标1。招募一组近期发生AP或RAP的非糖尿病患者， 使用频繁采样的静脉内注射来表征他们的胰岛自身免疫和葡萄糖/胰岛素稳态。 出院后1个月进行葡萄糖耐量试验和混合餐耐量试验，并在3，6， 12、18和24个月，此后每年。这一目标的目的是：（a）确定糖尿病的发病率 AP后，（B）识别AP后发展的糖尿病类型，（c）识别早期代谢轨迹 （d）集合将作为目标2-4的平台的群组。 具体目标2。评估AP或RAP患者糖尿病的遗传和蛋白质风险因素。这一目标 将评估T1 DM和T2 DM遗传风险评分与AP后糖尿病的相关性。13候选人 在初步研究中，将评估与AP后糖尿病相关的蛋白质与事件的相关性， AP后的糖尿病，产生一组关键蛋白质，不仅可用于糖尿病预测，还可用于靶向 未来的预防或治疗措施。 具体目标3。表征预测AP或RAP后糖尿病发展的成像表型。 在AP住院期间获得的回顾性CT扫描以及CT和新型多参数MRI 1个月和12个月后获得的扫描将进行人工智能分析，以识别成像 标志糖尿病风险的生物标志物。 具体目标4。开发一个多因素模型来预测AP或RAP后糖尿病的发展。了丰富 将从目标1-3中收集的数据，将与临床因素相结合，以建立和验证（在 独立数据集）AP后糖尿病的综合预测模型。我们的目标是创建一个模型， 可以在临床环境中使用，以确定那些处于最高风险的人，促进有针对性的措施，以预防糖尿病。 这项创新的研究将由一个经验丰富的内分泌学研究团队进行， 胃肠病学、影像学、生理学和流行病学，以解决具有重大公共卫生意义的问题。

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.