Administrative Supplement (NoD)

 描述（由申请人提供）：美国国立卫生研究院已拨款建立一个学术医疗中心联盟，利用这个联盟来发现胰腺炎、胰腺癌和糖尿病之间的新的潜在机制。佛罗里达大学完全准备好为这个联盟做出贡献。几十年来，UFHealth 学术医疗中心一直是这些疾病的区域资源，导致大量临床病例。广泛的专业知识和转化研究基础设施已经到位。在此应用中，我们展示了在吸引患者参与研究方面的持续生产力、与我们的 CTSI 生物样本库合作相关生物样本的高采购率，以及对这些疾病的独立研究努力，这些都激发了我们为联盟做出贡献的热情。该应用程序还为代表胰腺炎、糖尿病和胰腺癌患者的 3 个入口的临床小组之间加强合作提供了机会；胃肠科 (C. Forsmark, PD/PI)、内分泌科 (K. Cusi, PD/PI) 和普通外科 (S. Hughes, PD/PI)。这些调查人员在行政上领导各自的部门，也代表了 感兴趣的疾病方面的专业知识（C. Forsmark，胰腺炎；K. Cusi，糖尿病；S. Hughes，胰腺癌）。具体目标 1：描述慢性胰腺炎和糖尿病共存患者的代谢特征，并确定基础代谢特征的作用以及治疗效果对临床结果的影响。具体目标 2： 确定与胰腺炎相关的基因的已知基因组变异与疾病结果之间的纵向关系。具体目标 3：确定慢性胰腺炎和胰腺癌的局部炎症环境与疾病特异性结果和糖尿病的发展有何关系。总之，这项拟议的工作跨越了知识缺陷的关键领域：代谢特征/糖尿病亚型对长期结果的作用、3c型糖尿病的代谢组学、导致慢性胰腺炎和可能胰腺癌的遗传机制，以及胰腺内全身和局部的炎症状态，作为观察到的胰腺炎、胰腺癌和糖尿病之间关系的潜在机制来源，诊断/预后生物标志物和新的治疗靶点。

 DESCRIPTION (provided by applicant): The NIH has allocated funds for the establishment of a consortium of academic medical centers to use this collective to discover new underlying mechanisms that link pancreatitis, pancreatic cancer, and diabetes. The University of Florida is perfectly poised to contribute to this consortium. The UFHealth academic medical center has been a regional resource for these diseases for decades, resulting in high clinical volumes. Extensive expertise and translational research infrastructure are already in place. In this application, we demonstrate sustained productivity in the accrual of patients into research studies, high rates of procurement of relevant biospecimens in collaboration with our CTSI biorepository, and independent research efforts into these diseases that anchor our passion to contribute to the consortium. This application also represents an opportunity for increased collaboration between the clinical groups that represent the 3 portals of entry of patients with pancreatitis, diabetes, and pancreatic cancer; the Divisions of Gastroenterology (C. Forsmark, PD/PI), Endocrinology (K. Cusi, PD/PI), and General Surgery (S. Hughes, PD/PI). These investigators, who administratively lead their respective divisions, also represent an alignment of expertise in the diseases of interest (C. Forsmark, pancreatitis; K. Cusi, diabetes, and S. Hughes, pancreatic cancer). Specific Aim 1: To characterize the metabolic profile of patients with coexistent chronic pancreatitis and diabetes mellitus, and establish the role of the underlying metabolic profile, and the effect of treatment, to clinical outcomes. Specific Aim 2: To identify the longitudinal relationship(s) between known genomic variants of genes associated with pancreatitis and disease outcome. Specific Aim 3: To determine how the local inflammatory milieu in chronic pancreatitis and pancreatic cancer is related to disease specific outcomes and the development of diabetes. In summary, this proposed work spans critical areas of knowledge deficit: the role of metabolic profiles/diabetes subtypes to long-term outcomes, metabolomics of Type3c diabetes, genetic mechanisms leading to chronic pancreatitis and possibly pancreatic cancer, and the inflammatory state - both systemic and localized within the pancreas as a potential source of mechanistic contribution to the observed relationships between pancreatitis, pancreatic cancer, and diabetes, diagnostic/prognostic biomarkers and novel therapeutic targets.