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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

基本信息

批准号：
10631985
负责人：
Philip Richard Gehrman
金额：
$ 69.34万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
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/10631985
关键词：
Acclimatization Acute 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 biomarker panel circadian clinical application clinical diagnosis clinical subtypes cohort common symptom comorbidity design diagnostic strategy 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

项目摘要

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，与严重的痛苦和减损。失眠的评估依赖于患者的自我报告，而患者的自我报告往往受到许多因素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复杂化。此外，的子类型失眠可能基于睡眠时间短的存在或不存在。一种生物的鉴定可以促进评估和分型的失眠症的“特征”将显著改善症状管理层。代谢生物标记物在满足这一需求方面有很大的希望。患有失眠症的个人与睡得好的人相比，表现出新陈代谢的高度觉醒。在实验室里严重扰乱睡眠对新陈代谢的影响，但这些发现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，有一个明显的新陈代谢特征来自睡眠良好者的失眠患者。因此，这项研究的目的是调查慢性失眠和睡眠不足对代谢的影响。为了验证这一假设，我们将在- 四组(每组25人)100名受试者睡眠和代谢的深度表型：1) 有失眠和客观睡眠不足(<lt；6小时)的患者；2)没有失眠的患者目标短睡者(&gt；6小时)；3)习惯性短睡者(&lt；6小时)，无失眠迹象；以及4) 睡得好的人。家庭通宵多导睡眠图和动作图将被用来排除共病睡眠呼吸紊乱，并确认存在失眠。所有受试者都将参加为期四天的住院治疗人类物候学中心的协议。食物摄入量将以每小时等卡路里的零食形式提供，以控制饮食引起的新陈代谢变化。头两天将用来让受试者适应环境和餐饮。在第三天的早上，他们将放置一根留置血液的导管每晚每隔两小时采样一次，持续48小时，进行夜间多导睡眠监测。在这段时间里照明辐射水平将一直保持暗淡(&lt；250勒克斯)，以最大限度地减少光照对昼夜节律的影响。将使用核磁共振和质谱学对血清样本进行代谢组学分析。血样样本还将用于褪黑激素和皮质醇的检测，作为昼夜节律的标准标记。这个支持这一建议的全球假说是慢性失眠、睡眠不足及其组合与全身性代谢失调的不同特征有关。