Diabetes Timing and Types and the Effect on Beta Cell Function Post-Acute Pancreatitis in Children

儿童急性胰腺炎后糖尿病发生的时间和类型以及对 β 细胞功能的影响

• 批准号: 10554350
• 负责人: Maisam Abu-El-Haija
• 金额: $ 11.36万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10554350
• 关键词: Adult; Age; Antibodies; Applications Grants; Autoimmune; Award; Beta Cell; Biological Markers; Blood; Cell physiology; Child; Childhood; Classification; Clinical; Data; Dedications; Development; Diabetes Mellitus; Diagnosis; Disease; Emergency department visit; Etiology; Fasting; Functional disorder; Funding; Generations; Glucose; Goals; Guide prevention; Health Care Costs; Hospitalization; Impairment; Incidence; Infrastructure; Insulin Antibodies; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; K-Series Research Career Programs; Knowledge; Life Expectancy; Measures; Medical center; Methods; Modeling; Morbidity - disease rate; Multicenter Trials; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Nature; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Pancreatic Polypeptide; Patient-Focused Outcomes; Patients; Pattern; Pediatric Hospitals; Pediatrics; Peptides; Persons; Physiological; Population; Prediabetes syndrome; Prevention; Prospective Studies; Registries; Research; Research Design; Risk; Risk Factors; Role; Sampling; Standardization; Testing; Therapeutic; Time; Translating; United States; Variant; Work; acute pancreatitis; biobank; chronic pancreatitis; cohort; cystic fibrosis related diabetes; design; diabetes risk; feasibility testing; gastrointestinal; glucose metabolism; improved; indexing; innovation; insulin secretion; islet; longitudinal, prospective study; novel; patient subsets; predictive modeling; prognostic significance; prospective; response; sample collection; screening

Project Summary/Abstract The incidence of Acute Pancreatitis (AP) in children has been rising to 1/10,000 cases. Diabetes mellitus (DM) can result from AP in a subset of patients, and that leads to increased morbidity especially if underdiagnosed, given that there is no current method for DM screening post AP in the pediatric population. Post AP DM remains understudied with outcomes poorly defined. Previous studies in DM post AP are mostly single-centered and retrospective in nature, and thereby insufficient for understanding the natural history. From our previous work we have found up to 30% of children develop pre-DM or DM post AP and that a subset of patients have islet auto antibodies (Ab) positive testing post AP but that does not always translate to a full diagnosis of DM. This begs the question whether these Ab influence beta cell (β-cell) function and play a role in the progression to DM and what type of DM follows AP. Markers of DM types or β-cell function have not been studied post AP in pediatrics. Thus, this proposed study leverages our previous work in a novel design that allows for systematic generation of novel mechanistic data to define DM type, and the role of islet auto Abs and β-cell dysfunction as factors involved. The primary goal of this R03 are to investigate types of DM and extent of β-cell dysfunction from samples and subjects in prospective AP registry and biorepository at Cincinnati Children's Hospital Medical Center (CCHMC) generated under our NIDDK K23DK118190 designed to build predictive models for diabetes post AP. The primary objective of this project is to improve understanding of post AP DM, which will lead to improved patients' outcomes. This will be accomplished through our prospective longitudinal study design. Specific Aim 1 will define subtypes of DM and the temporal changes in relation to timing of Pre DM and DM post AP by testing for Type 1, Type 2 and Type 3c DM markers at different time points (3 and 12 months post AP). Specific Aim 2 will test the feasibility of conducting the standardized mixed meal tolerance testing (MMTT) in patients at 3 month and 12 month post AP, construct a model to define optimal samples collection time points needed for measuring β-cell responses to a stimulated test, and whether data points from stimulated testing provide value beyond simple fasting C peptide and glucose levels. The latter is important because MMTT is more cumbersome for pediatrics than a simple blood draw. We will also investigate the role of islet Ab positivity on β-cell function. Our proposal will help us better define progression to prediabetes then diabetes post AP to fill this knowledge gap. Successful completion of this study has the potential to lead to improved understanding of the mechanisms and risk factors for Pre-DM and DM, which will guide ultimately prevention and timely treatment of DM and its effect on children post AP.

项目摘要/摘要 儿童急性胰腺炎（AP）的事件已上升到1/10,000例。糖尿病（DM） 可能是由一部分患者中的AP引起的，这会导致发病率升高，尤其是在诊断未诊断的情况下， 鉴于儿科人群中没有目前的DM筛查后AP方法。 AP DM后仍然可以理解其定义较差的结果。以前在DM Post AP中的研究主要是 本质上以单一为中心和回顾性，因此不足以理解自然历史。从 我们以前的工作我们发现多达30％的儿童发展了DM或DM POST AP，并且该子集的子集 患者具有胰岛自动抗体（AB）阳性测试后AP，但并不总是转化为完整的 DM的诊断。这就提出了一个问题，这些AB是否影响Beta细胞（β细胞）功能并在 DM的进展以及AP随后的DM类型。 DM类型或β细胞功能的标记尚未 在儿科研究了AP。这是，这项拟议的研究利用了我们以前的工作 允许系统地生成新型机械数据来定义DM类型，以及胰岛自动ABS和 β细胞功能障碍是涉及的因素。该R03的主要目标是研究DM的类型和范围 辛辛那提的前瞻性AP注册表中的样本和受试者的β细胞功能障碍 我们的NIDDK K23DK118190生成的儿童医院医疗中心（CCHMC）旨在建造 糖尿病的预测模型AP。 该项目的主要目的是提高对AP DM的了解，这将改善 患者的结果。这将通过我们的前瞻性纵向研究设计来实现。具体目标1 将通过测试来定义DM的亚型和与PRE DM和DM POST AP的时间相关的暂时变化 对于类型1，在不同时间点（AP后3和12个月）在不同的时间点（3和12个月）的类型2和类型3C DM标记。具体目标2 将在3个月的患者中测试进行标准化的混合进餐测试（MMTT）的可行性 AP后12个月，构建一个模型来定义测量所需的最佳样本收集时间点 β细胞对刺激测试的响应，以及刺激测试的数据点是否提供了超出 简单的空腹o和葡萄糖水平。后者很重要，因为MMTT对 小儿比简单的抽血。我们还将研究胰岛AB阳性对β细胞功能的作用。我们的 提案将帮助我们更好地定义AP前糖尿病前期的糖尿病前期的进展，以填补这一知识差距。 成功完成这项研究有可能提高人们对机制和 DM和DM的危险因素，这将指导最终预防和及时治疗DM及其效果 关于儿童邮政AP。