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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：
10650324
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/10650324
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 Recommendation Reporting Risk Sampling Sleep Sleep Deprivation Standardization Temperature Testing Toxicant exposure Triglycerides diabetes risk epidemiology study experimental study glucose metabolism glucose tolerance impaired glucose tolerance improved 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.

摘要三分之二的美国人经常报告睡眠不足。慢性睡眠不足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。习惯性睡眠少于建议的每晚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，睡眠时间短与睡眠时间增加之间存在联系， 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，从1天到14天的变化降低了原本健康的成年人的葡萄糖耐量。现在认识到睡眠限制会降低胰岛素敏感性。已经探索了多种其他致病途径，包括脑葡萄糖利用减少，交感神经活动增加，夜间皮质醇升高，然而，在自由放养的人类和先前的实验研究中，伴随着较长时间暴露在夜间人造光（ALAN），一种内分泌干扰物，昼夜节律最近人们认识到昼夜节律紊乱本身会损害葡萄糖新陈代谢.我们推测，ALAN持续时间延长引起的内分泌和昼夜节律紊乱可能导致由慢性睡眠限制引起的不良代谢作用。为了验证这个假设，我们将在受控实验室条件下系统评价健康成人的葡萄糖代谢（光，温度，饮食和活动模式），使用交叉设计，包括7天基线，7天睡眠，限制（每晚5小时）与（光：暗19：5）或不（光：暗14：10）ALAN，9天洗脱期，和另一个 7-有或没有ALAN的白天睡眠限制。葡萄糖代谢（使用静脉葡萄糖耐量试验和标准化混合进餐反应）和昼夜节律（使用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。了解是否扩展持续时间ALAN是一种主要的上游暴露，有助于睡眠限制引起的损害，葡萄糖代谢和随之而来的糖尿病风险的增加是重要的，睡眠不足通过阐明一种潜在的可改变的机制，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的不良代谢影响的对策。