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: 10684392
• 负责人: GREGORY J BEILMAN
• 金额: $ 10万
• 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/10684392
• 关键词: Address; Adult; Age; Anatomy; Ancillary Study; Antibodies; Area Under Curve; Autoantibodies; Autologous Transplantation; Beta Cell; Biological Markers; Blood Glucose; Body mass index; C-Peptide; Caring; Cell Death; Child; Clinic; Clinical; Clinical Research; Cohort Studies; Collaborations; Complement; Complex; Control Groups; Cross-Sectional Studies; DNA; Data; Defect; Development; Diabetes Mellitus; Disease; Drainage procedure; Endocrine; Endocrinologist; Enrollment; Environment; Functional disorder; Funding; Future; Gastroenterologist; Glucose; Glucose tolerance test; Goals; Hormonal; Hormone secretion; Hyperglycemia; Hypoglycemia; Infrastructure; Insulin; Insulin-Dependent Diabetes Mellitus; Intestines; Lateral; Lead; Malignant neoplasm of pancreas; Manuscripts; Medical; Minnesota; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Ohio; Operative Surgical Procedures; Pain; Pancreas; Pancreatectomy; Pancreatic Diseases; Pancreatic Polypeptide; Pancreaticoduodenectomy; Pancreaticojejunostomy; Pancreatitis; Participant; Patient Care; Patients; Physicians; Polypeptide Hormones; Prevention strategy; Procedures; Protocols documentation; Regulation; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Series; Site; Smoking History; Structure; Subgroup; Surgeon; Surgical Management; Testing; Time; Tissues; Total Pancreatectomy; Universities; acute pancreatitis; anticancer research; chronic pancreatitis; clinical care; clinical center; comparison group; design; diabetes risk; genetic risk factor; glucagon-like peptide 1; health related quality of life; high risk; illness length; incretin hormone; innovation; insulin secretion; insulin sensitivity; interest; intravenous glucose tolerance test; islet; metabolic phenotype; multidisciplinary; non-diabetic; novel; pain relief; participant enrollment; patient subsets; prevent; primary endpoint; protocol development; recruit; research study; response; sex; type I and type II diabetes; 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) 研究联盟正在推进以下疾病的护理： 患有外分泌疾病的患者，通过一系列的研究特别关注这三种疾病的重叠 多中心协作临床研究。明尼苏达大学 (UMN) 提供以下两种课程 为 CPDCP 做出实质性和创新性贡献的临床专业知识和学术环境。 UMN 为胰腺炎和胰腺癌提供最先进的临床护理，并接收患者 转诊复杂性急性胰腺炎和慢性胰腺炎 (CP) 的内镜和手术治疗 来自美国各地的 Bellin 和 Beilman 博士（Co-PI）将增加慢性胰腺炎相关糖尿病方面的专业知识 mellitus (CP-DM) 和胰腺外科目前为联盟成员。贝林和贝尔曼在一起 已与 CPDCP 内的多个主要研究人员建立了持续的合作关系，强调 该团队无缝融入现有 CPDCP 临床中心的能力。通过参与作为 UMN 已经为当前联盟结构内俄亥俄州立大学和 INSPPIRE 的子站点做出了贡献 辅助研究的开发、手稿以及 CPDPC 开发的 INSPPIRE 参与者的注册 和检测协议。总之，UMN 已经记录了其为 CPDCP 目标做出贡献的能力，并将 作为公认的临床中心增加价值。 作为 CPDPC 内的临床中心，我们将把患有胰腺炎的成人和儿童纳入现有的临床中心 CPDPC 研究包括 PROCEED、INSPPIRE 和 DETECT (AIM 1)。我们也将参与工作 组、方案和标准操作程序的制定以及新的辅助研究的提议。我们 建议在当前 CPDCP 工作的基础上，通过研究以下内容来定义 CP-DM 机制： 胰腺手术后葡萄糖失调和 CP-DM 的病理生理学和机制。胰 手术，包括手术引流、Whipple 手术或全胰腺切除术联合胰岛自体移植 从根本上改变胰肠解剖结构，并可能具有不同的内分泌机制 出现高血糖或低血糖；由于约 20% 的 CP 患者最终可能需要接受手术，因此 了解这一亚组患者的疾病非常重要，以便正确筛查、治疗并最终 预防CP-DM。对于 AIM 2，我们将招募接受过手术的 CP 患者（每个手术组 n=75）并且 内窥镜 CP 和健康对照组测试胰岛素、胰多肽 (PP) 和肠促胰岛素激素 混合膳食耐受性和频繁样本静脉注射葡萄糖耐量的分泌和胰岛素敏感性 进行测试以区分这些群体的血糖异常机制。对于 AIM 3，非糖尿病患者将重新接受治疗 12-18 个月后进行研究，以确定血糖调节进行性缺陷的危险因素。此外， 我们将评估新型探索性生物标志物（CP-DM 中不进行常规研究），包括 β 细胞标志物 死亡、遗传风险因素和β细胞自身抗体。