Cardiometabolic Risk of Shift Work: Sleep Loss vs. Circadian Disruption

轮班工作的心脏代谢风险：睡眠不足与昼夜节律紊乱

• 批准号: 7730682
• 负责人: Eve Van Cauter
• 金额: $ 69.33万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7730682
• 关键词: Cardiometabolic; Risk; Shift; Work; Sleep

DESCRIPTION (provided by applicant): Nearly 20% of the US working population is engaged in shift work. It is well recognized that shift work is associated with an increased risk of developing cardiovascular disease and diabetes but the mechanisms underlying this elevated cardiometabolic risk remain unclear. Shift work is generally associated with sleep loss and circadian misalignment. While sleep curtailment has been recently identified as a putative novel risk factor for obesity, diabetes and hypertension, the clinical significance of the internal synchrony of endogenous rhythms is a fundamental and as yet unanswered question of circadian biology. Our group has recently completed a laboratory study showing that short-term exposure to sleep loss with circadian misalignment is associated with cardiometabolic alterations that are not reversed when sleep is aligned and extended. By comparison, alterations observed following exposure to sleep loss without circadian misalignment are fully corrected after sleep extension. These laboratory findings provided for the first time evidence in support of adverse health consequences of circadian disruption independent of sleep loss. The overall goal of the present application is to test the hypothesis that shift workers, who are chronically exposed to circadian misalignment and sleep loss, have a higher cardiometabolic risk than day workers, and that both circadian misalignment and sleep loss contribute to the elevated cardiometabolic risk. We will measure markers of cardiometabolic risk that are rapidly and profoundly affected by reduced sleep duration and/or quality and perform a detailed assessment of the phase relationships between rhythms controlled by the central circadian pacemaker and rhythms of clock gene expression in peripheral tissue. We propose to study two groups of workers (i.e. day workers, shift workers) who are employed at the University of Chicago Medical Center and who have maintained their work schedules for at least one year. Following extended ambulatory monitoring of exposure to circadian misalignment and usual sleep duration, the subjects will undergo repeated detailed laboratory assessments of 1. internal desynchrony of circadian rhythms, including rhythms of circadian gene expression in leukocytes; 2. markers of cardiometabolic risk: glucose tolerance and insulin resistance assessed by intravenous glucose tolerance testing (ivGTT), high sensitivity C-reactive protein (hsCRP), 24-h profile of heart rate variability; 3. telomere length and telomerase activity in leukocytes, which are markers of biological aging that have been linked to cardiometabolic risk factors and are influenced by lifestyle. This work is expected to demonstrate the clinical significance of circadian misalignment for the millions of individuals involved in shift work and to suggest novel strategies to improve tolerance to shift work. Public Health Relevance: Nearly 20% of the US working population is engaged in shift work, a condition associated with an increased risk of developing cardiovascular disease and diabetes. The overall goal of this project is to define the respective roles of circadian misalignment versus sleep loss in the elevated cardiometabolic risk of shift work.

描述（由申请人提供）：近20%的美国工作人口从事倒班工作。众所周知，轮班工作与患心血管疾病和糖尿病的风险增加有关，但这种升高的心脏代谢风险的机制尚不清楚。轮班工作通常与睡眠不足和昼夜节律失调有关。虽然睡眠不足最近被认为是肥胖、糖尿病和高血压的一个新的风险因素，但内源性节律内部同步性的临床意义是昼夜节律生物学的一个基本问题，但尚未得到解答。我们的团队最近完成了一项实验室研究，表明短期睡眠不足与昼夜节律失调有关，这与心脏代谢改变有关，而当睡眠调整和延长时，这种改变不会逆转。相比之下，在没有昼夜节律失调的情况下暴露于睡眠不足后观察到的变化在睡眠延长后完全得到纠正。这些实验室研究结果首次提供了证据，支持昼夜节律紊乱对健康的不良影响与睡眠不足无关。本应用程序的总体目标是验证长期暴露于昼夜节律失调和睡眠不足的轮班工人比白班工人具有更高的心脏代谢风险的假设，并且昼夜节律失调和睡眠不足都导致心脏代谢风险升高。我们将测量受睡眠时间和/或质量减少迅速而深刻影响的心脏代谢风险标志物，并对由中央昼夜节律起搏器控制的节律与外周组织时钟基因表达节律之间的相位关系进行详细评估。我们建议研究两组工人（即日班工人和轮班工人），他们受雇于芝加哥大学医学中心，并且保持了至少一年的工作时间表。在对暴露于昼夜节律失调和正常睡眠时间的长期动态监测之后，受试者将接受重复的详细实验室评估。昼夜节律的内部不同步，包括白细胞中昼夜节律基因表达的节律；2. 心脏代谢风险指标：通过静脉葡萄糖耐量试验（ivGTT）、高敏c反应蛋白（hsCRP）、24小时心率变异性评估葡萄糖耐量和胰岛素抵抗；3. 白细胞中的端粒长度和端粒酶活性是生物衰老的标志，与心脏代谢风险因素有关，并受生活方式的影响。这项工作有望证明数百万轮班工作个体的昼夜节律失调的临床意义，并提出提高轮班工作耐受性的新策略。