Center for Identification and Study of Individuals with Atypical Diabetes Mellitus (U54)

非典型糖尿病个体识别和研究中心 (U54)

• 批准号: 9597055
• 负责人: ASHOK BALASUBRAMANYAM
• 金额: $ 250万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9597055
• 关键词: Adult; Affect; Ancillary Study; Autoantibodies; Autoimmune Diabetes; Autoimmune Process; Biological Markers; C-Peptide; Categories; Characteristics; Classification; Clinic; Clinical; Clinical Protocols; Cluster Analysis; Collaborations; Collection; Colorado; Communication; Complex; Complex Mixtures; Complication; Core Facility; DNA; DNA Sequencing Facility; Data; Data Analyses; Data Storage and Retrieval; Databases; Development; Diabetes Mellitus; Diagnosis; Disease; Enrollment; Environmental Risk Factor; Epigenetic Process; Etiology; Evaluation; Family Study; Florida; Foundations; Functional disorder; Future; Genetic; Genome; Genotype; Goals; Heterogeneity; Immunology; Indiana; Individual; Insulin; Insulin-Dependent Diabetes Mellitus; International; Investigation; Longitudinal Studies; Medical Genetics; Medicine; Metabolic; Mining; Mission; Mitochondria; Molecular; Molecular Diagnosis; Multicenter Trials; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Participant; Pathogenesis; Pathologic; Patient Recruitments; Patients; Phenotype; Physiology; Population; Proinsulin; Registries; Research; Research Personnel; Resources; Sampling; Scientist; Secure; Serum; Single Nucleotide Polymorphism; Subgroup; Surface; Symptoms; Syndrome; System; Therapeutic; Universities; Variant; Washington; Work; Youth; adiponectin; base; biobank; cohort; college; data sharing; database of Genotypes and Phenotypes; design; diabetes mellitus genetics; exome; follow-up; genetic analysis; genetic information; genetic registry; genetic variant; improved; insight; islet; learning strategy; metabolomics; mitochondrial genome; novel; novel diagnostics; novel therapeutics; outreach; patient registry; phenotypic data; polypeptide C; prospective; recruit; repository; treatment response; unsupervised learning; web site

Diabetes is traditionally classified in two broad categories: autoimmune Type 1 and obesity-related Type 2. Numerous phenotypically and etiologically distinct forms exist and are emerging, collectively termed “atypical diabetes” (AD), that do not fit into either category. We hypothesize that AD comprises a spectrum that includes numerous forms, both known (e.g, MODY/monogenic, Latent Autoimmune Diabetes of Adults, Ketosis-Prone Diabetes) and unknown. We propose to establish the Center for Atypical Diabetes Research and Evaluation (CADRE). The goals of CADRE are to (1) identify and define comprehensively the forms of AD; and (2) establish an extensive database and repository of biosamples from AD patients. Defining the forms of AD is challenging because the etiology of AD can range from a single gene variant to a highly complex mixture of genetics, epigenetics and environmental factors. To identify patients with AD, and then to define the forms, we will use a two-pronged approach. Approach (a) will use clustering analysis of genotypic and phenotypic data from diverse groups of patients with diabetes. We have recruited 15 domestic and international population cohorts with data on more than 33,000 patients with diabetes. Further, we have recruited six diabetes study clinics (Baylor College of Medicine [BCM], University of Washington [UW], Indiana University [IU], Emory University, University of Colorado, and SUNY Downstate) who will prospectively recruit patients. The Juvenile Diabetes Research Foundation will facilitate recruitment from patient groups. The Administrative Core at BCM will work with cohorts and clinics to obtain data. The University of South Florida (USF) will filter data for AD and separate patients into phenotypically homogenous clusters that can be diagnosed based on genetic and clinical features unique to the cluster. Approach (b) will identify monogenic, oligogenic and mitochondrial forms of AD from patients enrolled in genetics registries (BCM) and a family study with genetic data (Botnia). The BCM registries include patients referred to the Undiagnosed Disease Network. All patients will undergo whole-exome and mitochondrial genome sequencing (Cores at BCM), single-nucleotide polymorphism variant analysis (Oxford), metabolomic analysis (Duke) and phenotypic analysis of C-peptide, adiponectin, proinsulin, islet autoantibodies, and serum insulin DNA levels (Cores at UW and IU). To establish the database and biorepository, we will invite patients with AD to participate in sample donation and longitudinal follow-up via the cohorts and clinics. Data and samples will be transferred to the Database and Biorepository Core at USF, with input and tracking implemented using the successful framework developed by USF for large multicenter trials. Data will be made available through the NIDDK and a CADRE website and samples will be made available through ancillary study application. Ongoing patient recruitment to expand the database and biorepository will occur through the study clinics and clinician referral through the CADRE website. Overall, CADRE will be built on a foundation of existing, successful core facilities and computational systems to create a lasting resource that will substantially advance AD research.

传统上，糖尿病分为两类：自身免疫1型和肥胖相关类型2。 存在许多表格和病因上不同的形式，并且正在出现，共同称为“非典型” 糖尿病”（AD），不适合这两个类别。我们假设广告包括一个包括 许多形式都已知（例如，成人的Mody/Mody/单基因，潜在的自身免疫性糖尿病 糖尿病）和未知。我们建议建立非典型糖尿病研究和评估中心 （干部）。干部的目标是（1）识别和全面定义AD的形式； （2）建立 广泛的数据库和AD患者的生物样品存储库。定义广告的形式受到挑战 因为AD的病因范围从单个基因变异到高度复杂的遗传学混合物，所以 表观遗传学和环境因素。要识别AD患者，然后定义表格，我们将使用 两管齐下的方法。方法（a）将使用潜水员的基因型和表型数据的聚类分析 糖尿病患者组。我们已经招募了15个国内和国际人口同伙 超过33,000例糖尿病患者。此外，我们还招募了六个糖尿病研究诊所（贝勒学院） 医学[BCM]，华盛顿大学[UW]，印第安纳大学[IU]，埃默里大学，大学 科罗拉多州和纽约州立大学），他们可能会招募患者。少年糖尿病研究 基金会将支持患者群体的招聘。 BCM的行政核心将与队列合作 和诊所以获取数据。南佛罗里达大学（USF）将过滤AD的数据，并将患者分开 可以根据遗传和临床特征诊断出表的同质簇 簇。方法（b）将确定入学的患者的AD的单基因，寡聚和线粒体形式 遗传学注册表（BCM）和一项具有遗传数据（Botnia）的家庭研究。 BCM注册表包括患者 提到未诊断的疾病网络。所有患者都将接受全外视和线粒体基因组 测序（BCM的核），单核苷酸多态性变体分析（牛津），代谢组分析 （公爵）和C肽，脂联素，蛋白酶，胰岛自身抗体和血清胰岛素的表型分析 DNA水平（UW和IU的核心）。为了建立数据库和生物验证，我们将邀请AD患者 通过队列和诊所参与样品捐赠和纵向随访。数据和样本将是 转移到USF的数据库和生物位核心，并使用该输入和跟踪 USF成功为大型多中心试验而开发的框架。数据将通过 NIDDK和一个干部网站和样本将通过辅助研究应用程序提供。正在进行 患者招募以扩大数据库和生物座位的招聘将通过研究诊所和临床进行 通过干部网站推荐。总体而言，干部将建立在现有成功核心的基础上 设施和计算系统创建持久的资源，该资源将大大推动广告研究。