Year 7 Administrative Supplement to INSPPIRE 2

INSPPIRE 2 的第 7 年行政补充

• 批准号: 10469779
• 负责人: MARK E. LOWE
• 金额: $ 77.37万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469779
• 关键词: Acute; Administrative Supplement; Adult; Age; Aggressive course; Ancillary Study; Autoantibodies; Autoimmunity; Beta Cell; C-Peptide; Characteristics; Child; Childhood; Clinical; Cognitive Therapy; Cohort Analysis; Cystic Fibrosis Transmembrane Conductance Regulator; Defect; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Disease Progression; Endocrine; Environmental Risk Factor; Exocrine pancreatic insufficiency; Fibrosis; Functional disorder; Funding; Genes; Genetic; Genetic Risk; Genetic Screening; Glucagon; Glucose; Goals; Health Care Costs; Hyperlipidemia; Hypertriglyceridemia; Image; Impaired health; Incidence; Insulin; Interdisciplinary Study; International; Islet Cell; Modality; Natural History; Onset of illness; Outcome; Pain; Pancreatic Polypeptide; Pancreatitis; Pathogenicity; Patient Outcomes Assessments; Pediatric cohort; Peptides; Physiologic calcification; Prediabetes syndrome; Predisposing Factor; Prevalence; Prognostic Factor; Quality of life; Recurrence; Research Personnel; Risk; Risk Factors; SPINK1 gene; Susceptibility Gene; Testing; Therapeutic; United States National Institutes of Health; Variant; Work; acute pancreatitis; blood glucose regulation; burden of illness; chronic pancreatitis; cohort; demographics; disability; early onset; genetic risk factor; genetic variant; genomic locus; glucagon-like peptide 1; glucose tolerance; health related quality of life; innovation; insight; islet; longitudinal analysis; premature; prospective; response; risk variant

PROJECT SUMMARY Acute pancreatitis (AP) is increasingly recognized in children, with an incidence approaching that of adults. Most children with pancreatitis have a single, mild, acute episode that resolves without complications. However, a subset of children with AP develops recurrent episodes (defined as acute recurrent pancreatitis or ARP) and some progress to chronic pancreatitis (CP). Pediatric ARP and CP significantly impact quality of life and carry high healthcare costs. Few studies have been performed to characterize the natural history pediatric ARP and CP, to identify its risk factors and to determine predictors of disease course. As INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE), the first multicenter, multidisciplinary collaboration in pediatric pancreatitis, we determined that children with ARP harbor multiple genetic risk variants and rapidly transition to CP, exocrine pancreatic insufficiency (EPI) and diabetes mellitus (DM). The risk factors that predispose children to early onset pancreatitis, rapid progression to CP and premature loss of exocrine and endocrine function are not well-known. The objective of this application is to delineate the natural history of pediatric CP through careful prospective analysis of INSPPIRE 2 cohort, to define the impact of genetic modifiers on disease course and to determine the mechanisms involved in pancreatogenic diabetes mellitus (T3cDM). The overall hypothesis is that genetic factors predispose children to early onset CP, EPI, and DM. Our specific aims are: 1) Characterize pediatric CP, determine predictors of disease onset and progression; 2) Determine the impact of genetic variants on disease onset and progression; 3) Identify mechanisms underlying disturbed glucose regulation in pediatric ARP and CP. This project will provide insight into the pathophysiology of pediatric pancreatitis, investigate the impact of genetic variants on disease course and explore the mechanisms of early islet cell dysfunction in pediatric ARP and CP. Our long-term goal is to develop diagnostic modalities, prognostic factors and innovative treatment approaches for pediatric ARP and CP.

项目摘要 急性胰腺炎（AP）在儿童中越来越认识到发生率 成年人。大多数患有胰腺炎的儿童都有一个单一的，温和的急性发作可以解决 没有并发症。但是，一部分AP的儿童会发展复发情节 （定义为急性复发性胰腺炎或ARP），并有一些进展到慢性胰腺炎 （CP）。小儿ARP和CP显着影响生活质量，并承担较高的医疗费用。 很少进行研究以表征自然历史小儿ARP和CP的表征 确定其危险因素并确定疾病病程的预测因素。作为杀伤性 （小儿胰腺炎国际研究小组：寻找治疗方法），第一个多中心， 小儿胰腺炎的多学科合作，我们确定患有ARP的儿童 携带多重遗传风险变体，并迅速过渡到CP，外分泌胰腺 功能不全（EPI）和糖尿病（DM）。使儿童容易受到危险因素 早期发作胰腺炎，迅速发展为CP以及外分泌过早丧失和 内分泌功能不是众所周知的。此应用的目的是描述 小儿CP的自然病史通过对Insppire 2队列的仔细前瞻性分析到 定义遗传修饰剂对疾病病程的影响并确定机制 参与胰腺生成糖尿病（T3CDM）。总体假设是遗传 因素使儿童易于早期发作CP，EPI和DM。我们的具体目的是：1） 特征小儿CP，确定疾病发作和进展的预测指标； 2）确定 遗传变异对疾病发作和进展的影响； 3）确定机制 小儿ARP和CP中的基础葡萄糖调节。这个项目将提供 深入了解小儿胰腺炎的病理生理学，研究遗传的影响 疾病课程的变体并探讨早期胰岛细胞功能障碍的机制 小儿ARP和CP。我们的长期目标是发展诊断方式，预后因素 小儿ARP和CP的创新治疗方法。