Metabolic Reprogramming in Insomnia as a Function of Objective Sleep Duration

失眠中的代谢重编程作为目标睡眠持续时间的函数

• 批准号: 10224342
• 负责人: Philip Richard Gehrman
• 金额: $ 69.84万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-27 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10224342
• 关键词: Acute; Address; Biological; Biological Assay; Biological Markers; Blood; Blood specimen; Branched-Chain Amino Acids; Chronic; Chronic Insomnia; Circadian Rhythms; Clinical; Data; Distress; Eating; Electroencephalography; Environment; Environmental Risk Factor; Exhibits; Fructose; Future; Glucose; Home; Hour; Human; Hydrocortisone; Impairment; Individual; Indwelling Catheter; Inpatients; Laboratories; Laboratory Study; Lead; Lighting; Lipids; Mass Spectrum Analysis; Measurement; Measures; Melatonin; Mental Health; Metabolic; Metabolism; Modeling; NMR Spectroscopy; Nuclear Magnetic Resonance; Outcome; Oxidative Stress; Patient Self-Report; Patients; Periodicity; Phenotype; Plasma; Polysomnography; Population; Protocols documentation; Public Health; Quality of life; Reporting; Research; Sampling; Science; Serum; Severities; Severity of illness; Sleep; Sleep Apnea Syndromes; Sleep Deprivation; Sleep disturbances; Sleeplessness; Symptoms; Techniques; Testing; Time; accurate diagnosis; actigraphy; adverse outcome; base; biomarker panel; circadian; clinical Diagnosis; clinical application; clinical subtypes; cohort; common symptom; comorbidity; design; experience; improved; indexing; light effects; meetings; metabolic profile; metabolic rate; metabolome; metabolomics; novel diagnostics; phenomics; physical conditioning; poor sleep; sugar; symptom management; symptomatic improvement; treatment planning; young adult

Project Summary Insomnia is among the most commonly experienced symptoms and is associated with significant distress and impairment. The assessment of insomnia is reliant on patient self-report, which is often influenced by a number of factors other than illness severity, complicating accurate diagnosis and treatment. Further, subtypes of insomnia may exist based on the presence or absence of short sleep duration. Identification of a biological ‘signature’ of insomnia that could facilitate assessment and subtyping would dramatically improve symptom management. Metabolic biomarkers have significant promise for meeting this need. Individuals with insomnia demonstrate metabolic hyperarousal compared to good sleepers. Acute disruption of sleep in the laboratory impacts the metabolome but the extent to which these findings extrapolate to chronic sleep disturbance or insufficient sleep is unknown. Our own data indicate there is a clear metabolic signature that differentiates patients with insomnia from good sleepers. The objective of this study is therefore to investigate the effects of chronic insomnia and insufficient sleep on metabolic profiles. In order to test this hypothesis we will conduct in- depth phenotyping of sleep and metabolism in 100 subjects who are in one of four groups (n=25 per group): 1) patients with insomnia and objective short sleep (<6 hours) on actigraphy; 2) patients with insomnia without objective short sleep (>6 hours); 3) habitual short sleepers (<6 hours) without evidence of insomnia; and 4) good sleepers. Home overnight polysomnography and actigraphy will be used to rule out comorbid sleep disordered breathing and confirm the presence of insomnia. All subjects will participate in a four-day inpatient protocol in the Center for Human Phenomic Science. Food intake will be provided in hourly isocaloric snacks to control for meal-induced shifts in metabolism. The first two days will be used to acclimate subjects to the environment and meals. On the morning of day 3 they will have an indwelling catheter placed for blood sampling every two hours for 48 hours with overnight polysomnography each night. During this time lighting levels will be kept constantly dim (<250 lux) to minimize the effects of light exposure on circadian rhythms. Metabolomics analysis of serum samples will be carried out using NMR and mass spectroscopy. Blood samples will also be used for melatonin and cortisol assays as standard markers of circadian rhythmicity. The global hypothesis that motivates this proposal is that chronic insomnia, insufficient sleep, and their combination are associated with distinct profiles of systemic metabolic dysregulation.

项目摘要 失眠是最常见的症状之一，与严重的困扰和 损害。失眠的评估依赖于患者的自我报告，这通常受到数量的影响 疾病严重程度以外的其他因素，使准确的诊断和治疗变得复杂。此外，子类型 基于睡眠持续时间短或不存在可能存在失眠。鉴定生物学 失眠的“签名”可以促进评估和亚型会大大改善症状 管理。代谢生物标志物可以满足这一需求。失眠的人 与良好的卧铺相比，表现出代谢性高音。实验室的急性睡眠中断 影响代谢组，但这些发现将推断为慢性睡眠障碍或 睡眠不足是未知的。我们自己的数据表明，有一个明确的代谢签名 良好睡眠者失眠的患者。因此，这项研究的目的是研究 慢性失眠和代谢特征的睡眠不足。为了检验这一假设，我们将进行内部 在四组之一中的100名受试者中的睡眠和代谢深度表型（每组n = 25）：1） 动作学的失眠和客观短睡眠（<6小时）的患者； 2）失眠的患者没有 客观短睡眠（> 6小时）； 3）惯常的短卧铺（<6小时）没有失眠的证据；和4） 好的睡眠者。一夜之间的多个术语术和行动摄影将被用来排除合并的睡眠 呼吸无序并确认失眠的存在。所有受试者将参加为期四天的住院 人类现象科学中心的协议。食物摄入量将以每小时的等效点小吃提供 控制膳食引起的新陈代谢转移。前两天将用于适应对象 环境和餐点。在第三天的早晨，他们将有一个留下的导管 每天晚上，每两个小时采样一次，持续48小时。在此期间照明 水平将不断保持昏暗（<250 lux），以最大程度地减少光曝光对昼夜节律的影响。 血清样品的代谢组学分析将使用NMR和质谱法进行。血 样品还将用于褪黑激素和皮质醇测定法作为昼夜节律的标准标记。 激发该提议的全球假设是慢性失眠，睡眠不足及其结合 与全身代谢失调的不同特征有关。