Evaluating Longitudinal Relationships Between Circulating MicroRNAs and Risk for Type 2 Diabetes and Responses to Behavioral Interventions

评估循环 MicroRNA 与 2 型糖尿病风险和行为干预反应之间的纵向关系

• 批准号: 9975150
• 负责人: Elena Flowers
• 金额: $ 20.19万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975150
• 关键词: Address; Adult; Behavior; Behavior Therapy; Behavioral; Biological; Biological Assay; Biological Markers; Biology; Blood; Blood Glucose; Blood specimen; Chronic Disease; Complex; Control Groups; Data; Detection; Development; Diabetes Mellitus; Disease; Environment; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Etiology; Fasting; Flow Cytometry; Funding; Future; Gene Expression; Genetic; Incidence; Individual; Insulin Resistance; Intervention; Knowledge; Longitudinal Studies; Measures; Mediating; Metabolic syndrome; MicroRNAs; Mission; Non-Insulin-Dependent Diabetes Mellitus; Participant; Patients; Pharmacology; Physical activity; Plasma; Polymerase Chain Reaction; Precision Health; Predictive Factor; Prevalence; Prevention; Public Health; Randomized; Risk; Risk Factors; Risk Reduction; Risk stratification; Sampling; Serum; Specimen; Stretching; Subgroup; Testing; Time; United States National Institutes of Health; Validation; Visit; Yoga; base; behavioral pharmacology; biomarker identification; circulating microRNA; clinically significant; cost; design; diabetes prevention program; extracellular; group intervention; high risk; improved; individual variation; insight; insulin sensitizing drugs; inter-individual variation; novel; novel strategies; patient response; phenotypic data; precision medicine; predictive modeling; public health priorities; randomized trial; response; treatment response

Relationships Between Risk for Type 2 Diabetes, Restorative Yoga, and Circulating MicroRNAs Project summary Type 2 diabetes is priority for both public health and precision medicine. The etiology of type 2 diabetes is complex and both genetic and behavioral/environmental factors contribute to risk. Current approaches to risk prediction and risk reduction are limited because they fail to account for the interactions between risk factors. MicroRNAs regulate expression of genes in response to behavioral and environmental exposures. Circulating microRNAs, which are readily detectable in blood, are emerging as useful indicators of disease etiology and show changes in response to the environment and behaviors. We previously showed that circulating microRNAs are associated with risk for type 2 diabetes and response to an insulin sensitizing pharmacologic agent. Our own prior studies and others have been cross-sectional and therefore provided limited information about the insights that microRNAs may provide about the mechanisms underlying development of type 2 diabetes. The first aim of this study is to evaluate the trajectories of circulating microRNAs and fasting blood glucose over time. We will measure microRNAs in banked plasma samples from participants in the the recently completed 48-week NIH-funded randomized Practicing Restorative Yoga vs. Stretching for the Metabolic Syndrome (PRYSMS) trial that tested the effect of restorative yoga on fasting blood glucose in individuals at risk for type 2 diabetes (n=171). Participants in the restorative yoga group (n=88) had a significant decrease in fasting blood glucose after 12 months compared to an active stretching control group. The existing phenotypic data and biologic specimens collected at five time points in the PRYSMS trial provide an exceptional opportunity to evaluate the relationships between longitudinal changes in both microRNAs and fasting blood glucose in an extremely well characterized sample of individuals who underwent an intervention that decreased their fasting blood glucose. The second aim of this study is to determine whether microRNAs predict changes in fasting blood glucose after 12-months. Circulating microRNAs will be measured using a flow cytometry-based direct detection assay followed by validation of significant targets by quantitative polymerase chain reaction. This study will be the first to evaluate the relationships between circulating microRNAs and fasting blood glucose over time. This knowledge will improve our understanding of inter-individual variability in mechanisms underlying type 2 diabetes. These insights can be used to improve risk detection, risk stratification, and optimization of risk reduction interventions based on individual biology.

2型糖尿病风险、恢复性瑜伽和循环microRNAs之间的关系 项目摘要 2型糖尿病是公共卫生和精准医疗的优先事项。2型糖尿病的病因是 复杂的遗传和行为/环境因素都有助于风险。目前应对风险的办法 预测和减少风险是有限的，因为它们没有考虑到风险因素之间的相互作用。 microRNA调节基因表达以响应行为和环境暴露。循环 在血液中容易检测到的microRNA正在成为疾病病因学的有用指标， 表现出对环境和行为的反应变化。我们之前的研究表明， microRNA与2型糖尿病风险和胰岛素增敏药理学反应相关 剂我们之前的研究和其他研究都是横断面的，因此提供的信息有限。 关于microRNA可能提供的关于2型糖尿病发展机制的见解， 糖尿病本研究的第一个目的是评估循环microRNA和空腹血液的轨迹 随着时间的推移。我们将在最近的研究中测量来自参与者的库存血浆样本中的microRNA。 完成了为期48周的NIH资助的随机练习恢复性瑜伽与拉伸的代谢 综合征（PRYSMS）试验，测试了恢复性瑜伽对个体空腹血糖的影响， 2型糖尿病的风险（n=171）。恢复性瑜伽组（n=88）的参与者在 12个月后的空腹血糖与主动拉伸对照组进行比较。现有的表型 在PRYSMS试验的五个时间点收集的数据和生物标本提供了一个特殊的 评估微小RNA和空腹血液纵向变化之间关系的机会 葡萄糖在一个非常好的表征样本的个人谁经历了干预， 降低他们的空腹血糖。本研究的第二个目的是确定microRNA是否 预测12个月后空腹血糖的变化。将使用流式细胞仪测量循环microRNA。 基于细胞计数的直接检测试验，随后通过定量聚合酶验证重要靶标 链反应这项研究将是第一个评估循环microRNA和 空腹血糖随时间的变化。这些知识将提高我们对个体间差异的理解， 2型糖尿病的发病机制这些见解可用于改善风险检测、风险管理和风险管理。 基于个体生物学的分层和优化风险降低干预措施。