University of Minnesota Clinical Center for the Study of Pancreatic Disease

明尼苏达大学胰腺疾病研究临床中心

• 批准号: 10892391
• 负责人: GREGORY J BEILMAN
• 金额: $ 13.52万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-03 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10892391
• 关键词: Adult; Anatomy; Ancillary Study; Autoantibodies; Autologous Transplantation; Beta Cell; Biological Markers; Blood Glucose; Cell Death; Child; Clinical; Clinical Research; Collaborations; Complex; Control Groups; Defect; Development; Diabetes Mellitus; Disease; Drainage procedure; Endocrine; Enrollment; Environment; Functional disorder; Glucose; Goals; Hormone secretion; Hyperglycemia; Hypoglycemia; Insulin; Intestines; Lead; Malignant neoplasm of pancreas; Manuscripts; Medical; Minnesota; Ohio; Operative Surgical Procedures; Pain; Pancreas; Pancreatectomy; Pancreatic Diseases; Pancreatic Hormones; Pancreaticoduodenectomy; Pancreatitis; Patient Care; Patients; Polypeptide Hormones; Procedures; Protocols documentation; Regulation; Research Personnel; Risk; Risk Factors; Sampling; Series; Structure; Surgical Management; Testing; Total Pancreatectomy; Universities; acute pancreatitis; anticancer research; chronic pancreatitis; clinical care; clinical center; diabetes risk; genetic risk factor; incretin hormone; innovation; insulin sensitivity; intravenous glucose tolerance test; islet; non-diabetic; novel; pain relief; participant enrollment; patient subsets; prevent; protocol development; research study; working group

PROJECT ABSTRACT The Chronic Pancreatitis Diabetes Pancreatic Cancer (CPDPC) research consortium is advancing care for patients with exocrine disease, particularly focused on the overlap of these three conditions through a series of multicenter collaborative clinically-focused research studies. The University of Minnesota (UMN) offers both the clinical expertise and the academic environment to contribute substantially and innovatively to the CPDCP. The UMN provides state of the art clinical care for pancreatitis and pancreatic cancer, and receives patient referrals for endoscopic and surgical management of complex acute pancreatitis and chronic pancreatitis (CP) from across the U.S. Dr. Bellin and Beilman (Co-PIs) will add expertise on chronic pancreatitis-related diabetes mellitus (CP-DM) and pancreatic surgery to the current consortium membership. Together Bellin and Beilman have established ongoing collaborations with multiple lead investigators within the CPDCP, highlighting the ability of this team to integrate seamlessly into the existing CPDCP Clinical Centers. Through engagement as a sub-site for Ohio State and INSPPIRE within the current consortium structure, UMN has already contributed to ancillary studies development, manuscripts, and enrollment of participants in the CPDPC developed INSPPIRE and DETECT protocols. In summary, UMN has documented its ability to contribute to the CPDCP goals and will add value as a recognized Clinical Center. As a Clinical Center within the CPDPC, we will enroll adults and children with pancreatitis into the existing CPDPC studies including PROCEED, INSPPIRE, and DETECT (AIM 1). We will also participate in working groups, development of protocols and standard operating procedures, and proposal of new ancillary studies. We propose to build upon the current CPDCP efforts to define mechanisms of CP-DM by studying the pathophysiology and mechanisms of glucose dysregulation and CP-DM after pancreatic surgery. Pancreatic surgery including surgical drainage, Whipple procedure, or total pancreatectomy with islet autotransplant fundamentally alters the pancreatic-intestinal anatomy and may have different endocrine mechanisms by which hyperglycemia or hypoglycemia develop; since ~20% of patients with CP may have eventually surgery, it is important to understand disease in this subgroup of patients, in order to properly screen for, treat, and ultimately prevent CP-DM. For AIM 2 we will enroll patients with CP who have had surgery (n=75 per surgical group) and an endoscopic CP and healthy control groups to test insulin, pancreatic polypeptide (PP), and incretin hormone secretion and insulin sensitivity by mixed meal tolerance and frequent sample intravenous glucose tolerance testing to differentiate mechanisms of dysglycemia in these groups. For AIM 3, non-diabetic patients will be re- studied 12-18 months later to determine risk factors for progressive defects in glycemic regulation. In addition, we will assess novel exploratory biomarkers (not routinely studied in CP-DM) including markers of beta cell death, genetic risk factors, and beta cell autoantibodies.

项目摘要 慢性胰腺炎糖尿病胰腺癌（CPDPC）研究联盟正在推进护理 外分泌疾病的患者，尤其是通过一系列的三个疾病重叠 多中心协作以临床为中心的研究。明尼苏达大学（UMN）提供 临床专业知识和学术环境为CPDCP做出了基本和创新的贡献。 UMN为胰腺炎和胰腺癌提供最先进的临床护理，并接受患者 用于复杂急性胰腺炎和慢性胰腺炎（CP）的内窥镜和手术管理的转诊 来自美国的贝林博士和贝尔曼博士（Co-Pis）将增加有关慢性胰腺炎相关糖尿病的专业知识 当前财团会员资格的Mellitus（CP-DM）和胰腺手术。贝林和贝尔曼在一起 已经与CPDCP中的多个主要研究人员建立了持续的合作，强调了 该团队能够无缝集成到现有的CPDCP临床中心。通过参与 俄亥俄州州的子站点和当前财团结构内的Insppire，UMN已经有助于 CPDPC参与者的辅助研究开发，手稿和入学率开发了Insppire 并检测协议。总而言之，UMN记录了其为CPDCP目标做出贡献的能力，并将 增加价值作为公认的临床中心。 作为CPDPC中的临床中心，我们将招募成人和患有胰腺炎的儿童进入现有 CPDPC的研究包括进行，INSPPIRE和检测（AIM 1）。我们还将参加工作 小组，协议和标准操作程序的制定以及新辅助研究的建议。我们 建议通过研究CPDCP来定义CP-DM的机制的努力。 胰腺手术后葡萄糖失调和CP-DM的病理生理和机制。胰 手术，包括手术排水，鞭打手术或胰岛自动移植的全胰腺切除术 从根本上讲，从根本上改变胰腺肠解剖学，可能具有不同的内分泌机制 高血糖或低血糖发展；由于约有20％的CP患者可能最终进行了手术，因此 重要的是要在这一患者亚组中了解疾病，以便正确筛选，治疗并最终 防止CP-DM。对于AIM 2，我们将招募进行手术的CP患者（每个手术组n = 75）和 内窥镜CP和健康对照组，以测试胰岛素，胰多肽（PP）和肠降血糖素激素 分泌和胰岛素的敏感性和频繁样品静脉葡萄糖耐受性 测试以区分这些组血糖的机制。对于AIM 3，非糖尿病患者将被重新 研究12-18个月后，研究了血糖调节中进行性缺陷的危险因素。此外， 我们将评估新型的探索性生物标志物（未在CP-DM中进行常规研究），包括β细胞的标记 死亡，遗传危险因素和β细胞自身抗体。

项目成果

Diabetes following acute pancreatitis.

• DOI: 10.1016/s2468-1253(21)00019-4
• 发表时间: 2021-08
• 期刊: The lancet. Gastroenterology & hepatology
• 作者: Hart PA;Bradley D;Conwell DL;Dungan K;Krishna SG;Wyne K;Bellin MD;Yadav D;Andersen DK;Serrano J;Papachristou GI
• 通讯作者: Papachristou GI

Type 1 diabetes mellitus in patients with recurrent acute and chronic pancreatitis: A case series.

• DOI: 10.1016/j.pan.2020.12.006
• 发表时间: 2021-01
• 期刊: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
• 作者: Kharoud HK;Mettler T;Freeman ML;Trikudanathan G;Beilman GJ;Chinnakotla S;Downs E;Schwarzenberg SJ;Bellin MD
• 通讯作者: Bellin MD

A Reduced Pancreatic Polypeptide Response is Associated With New-onset Pancreatogenic Diabetes Versus Type 2 Diabetes.

与 2 型糖尿病相比，胰多肽反应降低与新发胰源性糖尿病相关。

• DOI: 10.1210/clinem/dgac670
• 发表时间: 2023
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Hart,PhilA;Kudva,YogishC;Yadav,Dhiraj;Andersen,DanaK;Li,Yisheng;Toledo,FredericoGS;Wang,Fuchenchu;Bellin,MelenaD;Bradley,David;Brand,RandallE;Cusi,Kenneth;Fisher,William;Mather,Kieren;Park,WalterG;Saeed,Zeb;Considine,
• 通讯作者: Considine,

Internet Cognitive-Behavioral Therapy for Painful Chronic Pancreatitis: A Pilot Feasibility Randomized Controlled Trial.

• DOI: 10.14309/ctg.0000000000000373
• 发表时间: 2021-06-18
• 期刊: Clinical and translational gastroenterology
• 影响因子: 3.6
• 作者: Palermo TM;Law EF;Topazian MD;Slack K;Dear BF;Ko YJ;Vege SS;Fogel E;Trikudanathan G;Andersen DK;Conwell DL;Yadav D;Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC)
• 通讯作者: Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC)

Urine Proteomics Reveals Sex-Specific Response to Total Pancreatectomy With Islet Autotransplantation.

• DOI: 10.1097/mpa.0000000000002063
• 发表时间: 2022-05-01
• 期刊: PANCREAS
• 影响因子: 2.9
• 作者: Bennike, Tue Bjerg;Templeton, Kate;Fujimura, Kimino;Bellin, Melena D.;Ahmed, Saima;Schlaffner, Christoph N.;Arora, Rohit;Cruz-Monserrate, Zobeida;Arnaout, Ramy;Beilman, Gregory J.;Grover, Amit S.;Conwell, Darwin L.;Steen, Hanno
• 通讯作者: Steen, Hanno