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

2型糖尿病风险、恢复性瑜伽与循环微核糖核酸的关系 项目总结 2型糖尿病是公共卫生和精准医学的优先事项。2型糖尿病的病因是 复杂的遗传和行为/环境因素都会导致风险。当前的风险应对方法 预测和风险降低是有限的，因为它们没有考虑到风险因素之间的相互作用。 MicroRNAs调节基因的表达，以响应行为和环境暴露。流通中 在血液中很容易检测到的microRNAs，正在成为疾病病因学和 显示对环境和行为的响应变化。我们之前已经证明了循环 MicroRNAs与2型糖尿病的风险和对胰岛素增敏药物的反应有关 探员。我们之前的研究和其他研究都是横截面的，因此提供的信息有限 关于microRNAs可能提供的关于2型发展的潜在机制的见解 糖尿病。这项研究的第一个目的是评估循环中的microRNA和空腹血液的轨迹 随着时间的推移，葡萄糖。我们将在最近的研究中检测来自参与者的银行血浆样本中的microRNA 完成由美国国立卫生研究院资助的为期48周的恢复性瑜伽与为新陈代谢而伸展的随机练习 综合症(PRYSMS)试验，测试恢复性瑜伽对个人空腹血糖的影响 患2型糖尿病的风险(n=171)。恢复性瑜伽组(n=88)的参与者在 12个月后空腹血糖与主动伸展对照组进行比较。现有的表型 在PRYSMS试验的五个时间点收集的数据和生物样本提供了一个特殊的 评估microRNA纵向变化与空腹血液之间关系的机会 在接受了干预的个体样本中，血糖的特征非常好 降低他们的空腹血糖。这项研究的第二个目标是确定microRNA是否 预测12个月后空腹血糖的变化。循环中的microRNA将使用流动测量 基于细胞学的直接检测和定量聚合酶验证重要靶点 连锁反应。这项研究将首次评估循环中的microRNAs与 随着时间的推移，空腹血糖。这一知识将有助于我们更好地理解 2型糖尿病的发病机制。这些见解可以用来改进风险检测、风险 基于个体生物学的风险降低干预措施的分层和优化。

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.