Influence of Nocturnal Light Exposure on the Impairment of Glucose Tolerance Induced by Chronic Sleep Restriction

摘要 三分之二的美国人报告说，他们经常睡眠不足。慢性睡眠不足是 与一系列负面健康后果有关，包括肥胖、心血管疾病、 糖尿病和代谢综合征。习惯于每晚睡眠时间少于建议的7小时 与全因死亡率增加和代谢综合征相关死亡风险增加有关， 前瞻性的流行病学研究发现，睡眠时间短与睡眠增加之间存在关联。 患2型糖尿病的风险。实验室研究表明，睡眠限制在每晚4-6小时，持续时间 从1天到14天的变化降低了其他健康成年人的葡萄糖耐量。现在人们认识到， 限制睡眠会降低胰岛素敏感度。已经探索了多种额外的致病途径， 包括大脑葡萄糖利用率降低，交感神经活动增加，晚上皮质醇升高 水平等。然而，在自由放养的人类和之前的实验研究中，睡眠限制是 伴随着夜间长时间暴露在人造光中(艾伦)，一种内分泌干扰物，可能会扰乱 昼夜节律性。最近人们认识到，昼夜节律紊乱本身会损害血糖。 新陈代谢。我们假设艾伦持续时间过长引起的内分泌和昼夜节律紊乱可能 导致慢性睡眠限制引起的不良代谢影响。为了检验这一假设，我们将 在受控实验室条件下系统评估健康成年人的葡萄糖代谢(光， 温度、饮食和活动模式)使用由7天基线、7天睡眠组成的交叉设计 限制(每晚5小时)，有(光明：黑暗19：5)或没有(光明：黑暗14：10)艾伦，9天洗涤，以及另一种 有没有艾伦的7天睡眠限制。葡萄糖代谢(使用静脉葡萄糖耐量试验 和标准化的混合进餐反应)和昼夜节律(使用24小时血浆褪黑素和 皮质醇)将在每个睡眠限制段之前和之后进行评估。了解是否已扩展 持续时间艾伦是一种主要的上游暴露，导致睡眠受限诱导的脑功能损害 考虑到糖尿病的广泛流行，葡萄糖代谢和随之而来的糖尿病风险增加是重要的 睡眠不足。通过澄清睡眠限制负面影响的潜在可修改机制 全身能量动态平衡，我们的发现将为开发新的治疗方法奠定基础 以及减轻慢性睡眠限制对代谢的不利影响的对策。

ABSTRACT Two-thirds of Americans report regularly obtaining an insufficient amount of sleep. Chronic sleep deficiency is associated with a multitude of negative health consequences, including obesity, cardiovascular disease, diabetes, and metabolic syndrome. Habitually sleeping less than the recommended seven hours per night has been linked to increased all-cause mortality and increased risk of mortality associated with metabolic syndrome, and prospective epidemiological studies have found an association between short sleep duration and increased risk of type 2 diabetes. Laboratory studies have shown that sleep restriction to 4-6 hours per night for durations varying from one to 14 days reduces glucose tolerance in otherwise healthy adults. It is now recognized that sleep restriction decreases insulin sensitivity. Multiple additional causative pathways have been explored, including reduced brain glucose utilization, increased sympathetic nervous activity, elevated evening cortisol levels, etc. However, sleep restriction in both free-ranging humans and prior experimental studies is accompanied by longer exposure to Artificial Light At Night (ALAN), an endocrine disruptor which can disrupt circadian rhythmicity. It has recently been recognized that circadian disruption itself can impair glucose metabolism. We hypothesize that endocrine and circadian disruption caused by extended duration ALAN may contribute to the adverse metabolic effects induced by chronic sleep restriction. To test this hypothesis, we will systematically evaluate glucose metabolism in healthy adults in controlled laboratory conditions (light, temperature, diet and activity patterns) using a crossover design consisting of a 7-day baseline, 7-day sleep restriction (to 5h per night) with (Light:Dark 19:5) or without (Light:Dark 14:10) ALAN, 9-day washout, and another 7-day sleep restriction with or without ALAN. Glucose metabolism (using an intravenous glucose tolerance test and a Standardized Mixed Meal Response) and circadian rhythms (using 24-h profiles of plasma melatonin and cortisol) will be assessed before and after each sleep restriction segment. Understanding whether extended duration ALAN is a primary upstream exposure that contributes to the sleep-restriction-induced impairment of glucose metabolism and consequent increase in diabetes risk is important given the widespread prevalence of sleep deficiency. By clarifying a potential modifiable mechanism by which sleep restriction adversely affects whole-body energy homeostasis, our findings will lay the groundwork for the development of novel treatments and countermeasures to mitigate the adverse metabolic effects of chronic sleep restriction.