Indiana University clinical Center for acute pancreatitis and diabetes clinical research network

印第安纳大学急性胰腺炎和糖尿病临床中心临床研究网络

基本信息

批准号：
10673629
负责人：
Carmella Evans-Molina
金额：
$ 27.26万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
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/10673629
关键词：
3-Dimensional Address Adult Affect Alpha Cell Ancillary Study Arginine Artificial Intelligence Autoantibodies Beta Cell Biological Biological Markers Cell Death Cell physiology Cellular Stress Cellular biology Clinical Clinical Research Closure by clamp Collaborations Complication Data Defect Development Diabetes Mellitus Diffusion Magnetic Resonance Imaging Disease Duodenum Endocrine Enrollment Epidemiology Etiology Evolution Exhibits Exocrine pancreas Exocrine pancreatic insufficiency Extracellular Matrix Fatty acid glycerol esters Functional disorder Genetic Genomic DNA Glucagon Glucose Glucose Intolerance Goals Health Hyperglycemia Image Imaging Techniques Immune Immunologics Impaired fasting glycaemia Impairment Incidence Indiana Individual Infiltration Insulin Insulin Resistance Insulin deficiency Insulin-Dependent Diabetes Mellitus Investigation Islet Cell Knowledge Liquid substance Longitudinal Studies Magnetic Resonance Magnetic Resonance Elastography Magnetic Resonance Imaging Measurement Measures Meta-Analysis Metabolic Metabolic dysfunction Methodology Monitor Morphology Motion Natural History Nested Case-Control Study OGTT Observational Study Pancreas Pancreatic Function Tests Pancreatitis Patients Perfusion Phenotype Physiological Plasma Population Qualifying Relaxation Reporting Research Personnel Risk Risk Factors Risk Marker Secretin Serum Signal Transduction Structure of beta Cell of islet Subgroup Techniques Testing Texture Time Tissues Universities Urine Work acute pancreatitis biobank biomarker development clinical center clinical phenotype clinical risk contrast enhanced diabetes mellitus genetics diabetic patient endocrine pancreas development euglycemia extracellular genetic analysis glucose tolerance immune activation impaired glucose tolerance insulin secretion insulin sensitivity islet autoimmunity islet cell antibody medical schools member metabolic phenotype multidisciplinary non-diabetic novel pancreas imaging participant enrollment polygenic risk score prospective radiomics repository response type I and type II diabetes

项目摘要

PROJECT SUMMARY / ABSTRACT Pancreatogenic diabetes, or type 3c diabetes (T3cDM), is a known complication of acute pancreatitis (AP). Recent data suggest that T3cDM occurs more commonly than previously recognized and exhibits a spectrum of defects including features that overlap aspects of both type 1 and type 2 diabetes. At present, the extent to which immune activation, β cell dysfunction, and insulin resistance occur following AP and the genetic, metabolic and imaging correlates of these phenotypes have not been characterized. To address these knowledge gaps, we have assembled a multidisciplinary team with expertise in pancreatitis and exocrine pathophysiology, diabetes, β cell biology, diabetes genetics, and pancreatic imaging at the Indiana University School of Medicine. The IU Clinical Center will work with other members of the Type 1 Diabetes in Acute Pancreatitis Consortium to test the hypothesis that T3cDM encompasses a heterogeneous combination of metabolic and potentially immunologic phenotypes that are determined by distinct underlying pathophysiologies. We propose the following specific aims (SA) to meet the goals of this RFA. SA #1: To perform an observational study of robustly characterized adults with AP in order to address knowledge gaps in the natural history and incidence of autoantibody-positive diabetes (AAb+), impaired glucose tolerance (IGT)/impaired fasting glucose (IFG), and diabetes occurring subsequent to AP. Enrolled participants will be longitudinally characterized with emphasis on identifying genetic, immunological, metabolic, and clinical risk factors for the development of AAb+, IGT/IFG, or T3cDM. We will use state-of-the-art immunologic phenotyping and measurements of pancreatic β cell function to define the physiologic basis for metabolic dysregulation in T3cDM after AP. In tandem, a biorepository will be developed for undertaking translational, mechanistic and biomarker investigations and ancillary studies. SA#2: The Imaging Morphology of Pancreas in Diabetic Patients following Acute Pancreatitis (IMMINENT) study aims to utilize novel quantitative magnetic resonance imaging techniques as a non-invasive biomarker to identify patients at risk for the development of post-AP T3cDM. This longitudinal study will evaluate pancreatic parenchymal morphologic and pathophysiologic changes following AP in AAb+, euglycemic, IGT and DM individuals. Imaging phenotypes will be correlated with the metabolic, genetic and immunological phenotypes established in SA#1. SA#3: To perform a nested case control study using state-of-the-art techniques to define the underlying pathophysiology of endocrine and exocrine function in the subgroup of AAb+ individuals with AP-associated metabolic dysfunction relative to those who remain normoglycemic. We will undertake detailed metabolic phenotyping to evaluate islet cell responses (i.e. β and alpha cell function) in parallel with arginine-augmented hyperglycemic clamp methodology to measure functional β cell mass, and endoscopic assessment to define the relationship between impaired exocrine and endocrine function in AAb+ T3cDM. We will utilize 25 individuals with AAb+ and IGT or T3cDM and compare findings to results in 25 normoglycemic individuals with negative autoantibodies from SA#1.

项目摘要 /摘要胰腺生成糖尿病或3C型糖尿病（T3CDM）是已知的急性胰腺炎并发症（AP）。最近的数据表明，T3CDM发生比以前认识的更常见，并且展示了一系列缺陷，包括重叠1型和2型糖尿病的特征。目前，在多大程度上免疫激活，β细胞功能障碍和AP和遗传，代谢和这些表型的成像相关性尚未表征。为了解决这些知识差距，我们已经组建了一个具有胰腺炎和外分泌病理生理学专业知识的多学科团队，糖尿病，印第安纳大学医学院的β细胞生物学，糖尿病遗传学和胰腺成像。 IU 临床中心将与急性胰腺炎联盟中1型糖尿病的其他成员合作，以测试 T3CDM包括代谢和潜在免疫学的异质组合的假设由不同的潜在病理生理决定的表型。我们提出以下特定目标（SA）实现此RFA的目标。 SA＃1：对成年人进行鲁棒性的观察性研究使用AP来解决自身抗体阳性糖尿病的自然史和事件中的知识差距（AAB+），葡萄糖耐量受损（IGT）/禁食葡萄糖（IFG），以及发生后发生的糖尿病 AP。注册参与者将以纵向特征，重点是识别遗传，免疫学， AAB+，IGT/IFG或T3CDM的代谢和临床风险因素。我们将使用最先进的胰腺β细胞功能的免疫表型和测量，以定义生理基础 AP后T3CDM中的代谢失调。同时，将开发一个生物座席翻译，机械和生物标志物研究和辅助研究。 SA＃2：成像形态急性胰腺炎后糖尿病患者的胰腺（迫在眉睫）研究旨在利用新的定量磁共振成像技术是一种非侵入性生物标志物，以识别有风险的患者 t3CDM后的开发。这项纵向研究将评估胰腺副型形态学和 AAB+，Eugycemic，IGT和DM个体AP后的病理生理变化。成像表型会与SA＃1中建立的代谢，遗传和免疫表型相关。 SA＃3：表演使用最新技术来定义的嵌套案例控制研究 AAB+个体的子组中的内分泌和外分泌功能，具有AP相关代谢功能障碍相对于那些保持正常血糖的人。我们将进行详细的代谢表型，以评估胰岛与精氨酸增强的高血糖夹并行的细胞反应（即β和α细胞功能）测量功能性β细胞量的方法和内镜评估以定义 AAB+ T3CDM中的外分泌和内分泌功能受损。我们将使用AAB+和IGT或IGT或 T3CDM并将发现与25个正常血糖个体进行比较，SA＃1具有负自身抗体。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The continuum of complications in survivors of necrotizing pancreatitis.

DOI：
10.1016/j.surg.2020.07.004
发表时间：
2020-12
期刊：
Surgery
影响因子：
3.8
作者：
Maatman TK;Roch AM;Ceppa EP;Easler JJ;Gromski MA;House MG;Nakeeb A;Schmidt CM;Sherman S;Zyromski NJ
通讯作者：
Zyromski NJ

DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life.

DOI：
10.1007/s00125-021-05513-4
发表时间：
2021-10
期刊：
Diabetologia
影响因子：
8.2
作者：
Thomas NJ;Dennis JM;Sharp SA;Kaur A;Misra S;Walkey HC;Johnston DG;Oliver NS;Hagopian WA;Weedon MN;Patel KA;Oram RA
通讯作者：
Oram RA

Biliary Stricture After Necrotizing Pancreatitis: An Underappreciated Challenge.

坏死性胰腺炎后胆道狭窄：一个未被充分认识的挑战。