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

夜间光照对慢性睡眠限制所致糖耐量损害的影响

基本信息

批准号：
10297979
负责人：
Charles A Czeisler
金额：
$ 77.82万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-29 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10297979
关键词：
Acute Adult Adverse effects Affect Age American Area Under Curve Brain Cardiovascular Diseases Chronic Circadian Dysregulation Circadian Rhythms Crossover Design Darkness Development Diabetes Mellitus Diet Endocrine Disruptors Endocrine disruption Exhibits Exposure to Glucose Goals Health Homeostasis Hour Human Hydrocortisone Impairment Intervention Laboratories Laboratory Study Light Lighting Link Lipids Mass Spectrum Analysis Measures Melatonin Metabolic Metabolic syndrome Non-Insulin-Dependent Diabetes Mellitus Obesity Participant Pathway interactions Pattern Periodicity Plasma Posture Prevalence Randomized Reporting Risk Sampling Sleep Sleep Deprivation Standardization Temperature Testing Toxicant exposure Triglycerides circadian diabetes risk epidemiology study experimental study glucose metabolism glucose tolerance impaired glucose tolerance insulin sensitivity intravenous glucose tolerance test mortality mortality risk novel prospective response sex

项目摘要

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.

抽象的三分之二的美国人表示经常睡眠不足。慢性睡眠不足是与多种负面健康后果相关，包括肥胖、心血管疾病、糖尿病和代谢综合征。习惯性地每晚睡眠时间少于建议的七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，前瞻性流行病学研究发现，睡眠时间短与睡眠时间增加之间存在关联。 2 型糖尿病的风险。实验室研究表明，将睡眠时间限制为每晚 4-6 小时 1 到 14 天不等，会降低其他健康成年人的葡萄糖耐量。现在人们认识到睡眠限制会降低胰岛素敏感性。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、夜间皮质醇升高然而，自由放养的人类和之前的实验研究中的睡眠限制是伴随着更长时间地暴露在夜间人造光 (ALAN) 下，这是一种内分泌干扰物，会扰乱昼夜节律。最近人们认识到昼夜节律紊乱本身会损害血糖代谢。我们假设 ALAN 持续时间延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。为了检验这个假设，我们将在受控实验室条件（光、温度、饮食和活动模式），采用交叉设计，包括 7 天基线、7 天睡眠限制（每晚 5 小时），有（浅色：深色 19:5）或没有（浅色：深色 14:10）ALAN，9 天冲洗，以及其他有或没有 ALAN 的 7 天睡眠限制。葡萄糖代谢（使用静脉内葡萄糖耐量试验和标准化混合膳食反应）和昼夜节律（使用 24 小时血浆褪黑激素和皮质醇）将在每个睡眠限制段之前和之后进行评估。了解是否扩展 ALAN 持续时间是主要的上游暴露，导致睡眠限制引起的损伤鉴于糖尿病的广泛流行，葡萄糖代谢和随之而来的糖尿病风险增加非常重要睡眠不足。通过阐明睡眠限制产生不利影响的潜在可修改机制全身能量稳态，我们的研究结果将为开发新疗法奠定基础以及减轻长期睡眠限制对代谢的不利影响的对策。