Center for Identification and Study of Individuals with Atypical Diabetes Mellitus

非典型糖尿病个体识别和研究中心

• 批准号: 10660917
• 负责人: Louis H. Philipson
• 金额: $ 250万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-10 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10660917
• 关键词: Affect; American; Area; Autoimmune; Biological; Biological Specimen Banks; Biology; Chicago; Clinical; Clinical Data; Clinical assessments; Collection; Communities; Consent; Data; Data Aggregation; Databases; Defect; Diabetes Mellitus; Disease; Enrollment; Equipment and supply inventories; Etiology; Family; Family member; Fostering; Future; General Population; Genes; Genetic; Genetic Heterogeneity; Genetic Variation; Genetic study; Genomics; Genotype; Grant; Heterogeneity; Individual; Institution; Investigation; Knowledge; Laboratories; Molecular Genetics; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Participant; Pathway interactions; Patient Recruitments; Penetrance; Phenotype; Physiological; Prevention; Principal Investigator; Process; Recording of previous events; Records; Research; Research Personnel; Resources; Retrieval; Risk; Sampling; Testing; Translational Research; Variant; Vision; Work; age related; biobank; cohort; data access; data integration; design; diabetes pathogenesis; exome sequencing; genetic analysis; genetic pedigree; genetic variant; insight; member; novel; novel strategies; programs; recruit; research study; response; treatment strategy; variant of interest; working group

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.

项目摘要 – 概述 抽象的 在这里，我们描述了我们对国家非典型个体识别和研究中心的愿景 糖尿病对 RFA-DK-17-006 的回应。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，是糖尿病的机构焦点 在全国范围内呼吁患有非典型糖尿病的受试者旨在： a) 促进对不明原因罕见/非典型糖尿病患者的研究； b) 识别和分析表型和基因型缺陷，这些缺陷可以提供对更常见的、 一般人群中 2 型糖尿病 (T2DM) 的异质形式；和 c) 开发社区资源，通过数据库推进该领域的研究，以促进 通过生物样本库和活体收集和传播表型和遗传数据 供糖尿病研究界访问的生物库。 我们的中心假设是，识别和研究罕见/非典型形式的新病例 糖尿病将使人们对 T2DM 的病因学和遗传异质性有更深入的了解。 该中心以过去三十年参与团体的记录为基础，将 支持主要研究工作： 我。以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为基础 糖尿病生物学开发和实施流程（基于谱系分析和战略 全外显子组测序）用于识别和研究患有罕见和罕见疾病的个人/家庭 未表征的糖尿病； 二.创建一个全国性的合作者网络，以帮助确定并初步对个体进行表型分析 已确定血统； 三.调整我们现有的基于 REDCap 的单基因糖尿病数据库来创建和管理研究 罕见/非典型糖尿病数据库、活体生物库和生物样本库以及公共 供糖尿病研究界在未来研究中使用的门户；和 四.通过提供生物库的访问权限，促进未来对遗传变异影响的研究 材料和活体生物库。 这些个体及其家人的详细表型、基因分型和基因测序将有助于 描述一般人群中 T2DM 谱系中存在的罕见非典型亚型，并揭示 涉及糖尿病发病机制的新机制途径。途径及其相关知识 组成分子应指出治疗和/或预防 T2DM 的新策略。

项目成果

Data Mining Framework for Discovering and Clustering Phenotypes of Atypical Diabetes.

用于发现和聚类非典型糖尿病表型的数据挖掘框架。

• DOI: 10.1210/clinem/dgac632
• 发表时间: 2023
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Parikh,HemangM;Remedios,CassandraL;Hampe,ChristianeS;Balasubramanyam,Ashok;Fisher-Hoch,SusanP;Choi,YeJi;Patel,Sanjeet;McCormick,JosephB;Redondo,MariaJ;Krischer,JeffreyP
• 通讯作者: Krischer,JeffreyP

SGLT-2 Inhibitors: Discrepancy Between MACE Reduction and Incident MI and Stroke.

SGLT-2 抑制剂：MACE 减少与 MI 和中风事件之间的差异。

• DOI: 10.1210/clinem/dgad216
• 发表时间: 2023
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Broome,DavidT

Investigator and participant expectations for returning non-genetic results: insights from the Rare and Atypical Diabetes Network (RADIANT) study.

• DOI: 10.1017/cts.2023.684
• 发表时间: 2023
• 期刊: JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE
• 影响因子: 2.6
• 作者: Noohi, Forough;Sundaresan, Manu S.;Naylor, Rochelle N.;Ross, Lainie Friedman
• 通讯作者: Ross, Lainie Friedman