Metabolic Reprogramming in Insomnia as a Function of Objective Sleep Duration

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。

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.