Biomarkers and Altered Metabolic Pathways during Sleep Loss and Circadian Disruption

睡眠不足和昼夜节律紊乱期间的生物标志物和代谢途径的改变

• 批准号: 10668411
• 负责人: Christopher Michael Depner
• 金额: $ 16.58万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-19 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10668411
• 关键词: Acceleration; Adult; Affect; American; Anxiety; Area; Award; Benchmarking; Biochemical; Biochemical Pathway; Bioinformatics; Biological; Biological Markers; Blood; Branched-Chain Amino Acids; Cardiometabolic Disease; Chronic; Circadian Dysregulation; Circadian Rhythms; Circadian desynchrony; Clinical assessments; Communities; Data; Data Analyses; Development; Diabetes Mellitus; Diagnosis; Disease; Drug abuse; Epidemic; Fingerprint; Funding; Glucose; Goals; Health; Health Benefit; Hour; Human; Individual; Inflammation; Intervention; Laboratories; Link; Mental Depression; Metabolic Diseases; Metabolic Pathway; Obesity; Outcome; Participant; Persons; Phenotype; Physiological; Plasma; Prevalence; Prevention; Proteins; Proteome; Proteomics; Protocols documentation; Public Health; Publishing; Recommendation; Research; Research Training; Risk; Sampling; Science; Sensitivity and Specificity; Sleep; Sleep Deprivation; Sleep Disorders; System; Testing; Time; Training; Translations; United States National Institutes of Health; Wakefulness; Weight Gain; Work; adequate sleep; aged; bench to bedside; biomarker identification; biomarker validation; cardiometabolic risk; cardiometabolism; circadian; clinical biomarkers; clinical diagnosis; clinical translation; cohort; diabetes risk; fatty acid metabolism; improved; insulin sensitivity; metabolome; metabolomics; novel; personalized medicine; poor sleep; primary care provider; primary outcome; programs; response; secondary outcome; shift work; timeline; week trial

PROJECT SUMMARY/ABSTRACT Approximately 50-70 million Americans suffer from sleep and wakefulness disorders and over 35% of Americans sleep less than the recommended 7 hours per night. Additionally, ~20% of adults in the work force are shift- workers and therefore have elevated risk of circadian misalignment (i.e. sleeping during the biological day and wakefulness during the biological night). Health problems associated with insufficient sleep and circadian misalignment include inflammation, depression and anxiety, drug abuse, reduced insulin sensitivity, diabetes, and obesity. While the contribution of sleep to overall health is well recognized, many primary care providers fail to diagnose or recognize sleep and circadian disorders and estimates show undiagnosed sleep disorders are more prevalent than diagnosed sleep disorders. Currently, no clinical biomarkers of overall sleep and circadian health exist. Developing such biomarkers has the potential to: 1) improve diagnosis of sleep and circadian disorders; 2) identify biochemical mechanisms underlying increased risk of cardiometabolic disease associated with insufficient sleep and circadian misalignment; and 3) inform novel sleep and circadian based countermeasures. Long-term, biomarkers of sleep and circadian health could also support the development of personalized medicine, in part, by identifying individuals most likely to benefit from sleep and circadian based interventions. The overall goal of this K01 is to identify biomarkers of sleep loss and circadian misalignment, and assess the impact of increased sleep time on these biomarkers. I will use samples from two previously completed NIH- funded laboratory based protocols to identify putative biomarkers of insufficient sleep and circadian misalignment using plasma metabolomics and proteomics. I will also assess the plasma metabolome and insulin sensitivity in a four-week trial that increases nightly sleep duration to the recommended ≥7 hours sleep/night in habitual short-sleepers to determine if my identified biomarkers can discriminate these individuals between baseline insufficient sleep and post-increased sleep time and if increasing sleep time improves insulin sensitivity. This award will provide key training in four areas: 1) bioinformatics; 2) omics; 3) clinical translational sleep and circadian studies and interventions; and 4) professional development, and will provide essential preliminary data for an NIH R01 to help me launch an independent research program. The proposed outcomes support the 2011 NIH Sleep Disorders Research Plan to “enable sleep and circadian research training to inform science in cross-cutting domains, accelerate the pace of discovery, and the translation of enhanced therapies from bench to bedside to community”.

项目摘要/摘要 大约有500-70万美国人患有睡眠和清醒障碍，超过35％的美国人 睡得低于建议每晚7个小时的建议。此外，劳动力中约有20％的成年人是转移 - 工人，因此患有昼夜节律的风险升高（即在生物学日和 在生物之夜的清醒）。与睡眠不足和昼夜节律相关的健康问题 未对准包括注射，抑郁和动画，药物滥用，胰岛素敏感性降低，糖尿病， 和肥胖。虽然睡眠对整体健康的贡献得到广泛认可，但许多初级保健提供者失败了 诊断或识别睡眠和昼夜疾病和估计表明睡眠障碍更多 比被诊断的睡眠障碍流行。目前，没有整体睡眠和昼夜节律的临床生物标志物 存在。开发这种生物标志物的潜力：1）改善睡眠和昼夜节律疾病的诊断； 2）确定与与心脏代谢疾病风险增加的生化机制相关的风险 睡眠不足和昼夜节律的未对准； 3）为新颖的睡眠和基于昼夜节律的对策提供信息。 长期的睡眠和昼夜节律生物标志物也可以支持个性化的发展 医学部分是通过确定最有可能受益于睡眠和昼夜节律干预措施的人。 该K01的总体目标是确定睡眠损失和昼夜节律未对准的生物标志物，并评估 我将使用两个先前完成的NIH-的样品 基于实验室的资助协议，以确定睡眠不足和昼夜节律的假定生物标志物 使用血浆代谢组学和蛋白质组学的未对准。我还将评估血浆代谢组和胰岛素 在为期四周的试验中，敏感性将每晚的睡眠时间增加到推荐的≥7小时/晚上的建议≥7小时 习惯性短暂的疲劳者，以确定我所识别的生物标志物是否可以区分这些人 基线睡眠不足和入后睡眠时间，如果睡眠时间增加会提高胰岛素的敏感性。 该奖项将在四个领域提供关键培训：1）生物信息学； 2）omics; 3）临床翻译睡眠和 昼夜研究和干预措施； 4）专业发展，并将提供基本的初步 NIH R01的数据可帮助我启动独立的研究计划。提出的结果支持 2011 NIH睡眠障碍研究计划“启用睡眠和昼夜研究培训，以告知科学 横切域，加速发现空间，以及增强疗法从长凳上的翻译 社区的床边”。