Center for Identification and Study of Individuals with Atypical Diabetes Mellitus

项目概要-概述 摘要 在这里，我们描述了我们的愿景，为国家中心的个人识别和研究非典型肺炎 糖尿病对RFA-DK-17 - 006的响应。该中心的目的是召集主要的糖尿病中心 具有糖尿病临床评估、遗传学和生理学研究方面的专业知识， 在全国范围内征集非典型糖尿病受试者，旨在： a）促进对不明原因的罕见/非典型糖尿病患者的研究; B）鉴定和分析表型和基因型缺陷，其可以提供对更常见的， 一般人群中的异质性2型糖尿病（T2DM）;以及 （c）开发社区资源，通过数据库促进这一领域的研究， 收集和传播表型和遗传数据，包括生物保藏样品和活体 糖尿病研究社区可以访问的生物库。 我们的中心假设是，罕见/非典型形式的新病例的识别和研究， 糖尿病将使我们更深入地了解T2DM的病因和遗传异质性。 该中心在过去三十年来参与团体的记录基础上，将 支持主要研究工作，以便： I.基于我们现有的单基因糖尿病资源、遗传学专业知识和对糖尿病的深入了解， 糖尿病生物学，以制定和实施流程（基于谱系分析和战略 全外显子组测序）用于鉴定和研究具有罕见和 糖尿病的非特征性形式; 二.建立一个全国性的合作者网络，以帮助确定和初步表现个体， 确定谱系; 三.调整我们现有的基于REDCap的单基因糖尿病数据库，以创建和管理研究 罕见/非典型糖尿病数据库，活体生物库和生物标本储存库，以及公共 供糖尿病研究界在未来研究中使用的门户网站;以及 四.通过提供生物库，促进未来对遗传变异影响的调查 材料和活体生物库。 这些个体及其家族的详细表型、基因分型和基因测序将有助于 描述一般人群中T2 DM谱系中存在的罕见非典型亚型的特征，并揭示 参与糖尿病发病机制的新机制途径。知识的途径和他们的 因此，研究T2DM的组成分子应该指出治疗和/或预防T2DM的新策略。

PROJECT SUMMARY – OVERVIEW ABSTRACT Here we describe our vision for the National Center for the Identification and Study of Individuals with Atypical Diabetes Mellitus in response to RFA-DK-17-006. The Center’s purpose is to convene key diabetes centers with expertise in the clinical assessment, genetics, and physiological study of diabetes as institutional foci of a nation-wide call for subjects with atypical forms of diabetes designed to: a) Foster the study of individuals with rare/atypical forms of diabetes mellitus of unknown cause; b) Identify and analyze phenotypic and genotypic defects that may provide insights into more common, heterogeneous forms of type 2 diabetes mellitus (T2DM) in the general population; and c) Develop a community resource to advance research in this area through a database to facilitate the collection and dissemination of phenotypic and genetic data with biorepository samples and a living biobank for access by the diabetes research community. Our central hypothesis is that the identification and study of new cases of rare/atypical forms of diabetes will yield greater insights into the etiology and genetic heterogeneity of T2DM. The Center, building on the track records of the participating groups over the last three decades, will support primary research endeavors to: i. Build on our existing monogenic diabetes resources, genetics expertise, and deep knowledge of the biology of diabetes to develop and implement processes (based on pedigree analysis and strategic whole exome sequencing) for identifying and studying individuals/families with rare and uncharacterized forms of diabetes; ii. Create a national network of collaborators to help ascertain and initially phenotype the individuals in pedigrees identified; iii. Adapt our existing REDCap-based monogenic diabetes database to create and manage a study database for rare/atypical forms of diabetes, a living biobank and biospecimen repository, and a public portal for use by the diabetes research community in future studies; and iv. Facilitate future investigation of the impact of genetic variation by providing access to biobanked materials and the living biobank. Detailed phenotyping, genotyping, and gene sequencing of these individuals and their families will help to characterize rare atypical subtypes present in the spectrum of T2DM in the general population, and reveal novel mechanistic pathways involved in the pathogenesis of diabetes. Knowledge of the pathways and their constituent molecules should point to novel strategies for the treatment and/or prevention of T2DM.