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: 8294372
• 负责人: Eve Van Cauter
• 金额: $ 75.57万
• 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/8294372
• 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％的美国工作人群从事轮班工作。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，但是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损失和昼夜节律错位有关。尽管睡眠减少最近被确定为肥胖，糖尿病和高血压的一种假定的新型危险因素，但内源性节奏内部同步的临床意义是昼夜节律生物学的基本且尚未得出的问题。我们的小组最近完成了一项实验室研究，该研究表明，短期暴露于昼夜节律未对准的睡眠损失与心脏代谢的变化有关，这些改变是在对齐和扩展睡眠时不会逆转的。相比之下，在睡眠延伸后，在没有昼夜节律未对准的情况下发生睡眠损失后观察到的改变。这些实验室发现提供了首次证据，以支持独立于睡眠损失的昼夜节律中断的不利影响。本应用的总体目标是检验以下假设：在长期暴露于昼夜节律失误和睡眠损失的转变工人中，心脏代谢风险比日常工作人员更高，并且昼夜节律失调和睡眠损失都会导致心脏代谢升高的风险。我们将测量心脏代谢风险的标志物，这些标志受到睡眠持续时间减少和/或质量的迅速和深刻影响，并对由中央昼夜节律起搏器控制的节奏与外周种组织中时钟基因表达的节奏进行详细评估。我们建议研究在芝加哥大学医学中心工作的两组工人（即一日工，轮班工人），并维持工作时间表至少一年。在对昼夜节律未对准和通常的睡眠持续时间的暴露进行扩展监测之后，受试者将对1次反复进行1次的详细实验室评估。昼夜节律的内部降解，包括在白细胞中昼夜节律基因表达的节奏； 2。心脏代谢风险的标记：通过静脉葡萄糖耐量测试（IVGTT）评估的葡萄糖耐量和胰岛素抵抗，高灵敏度C反应蛋白（HSCRP），24小时的心率变异性； 3。白细胞中的端粒长度和端粒酶活性，它们是与心脏代谢危险因素有关的生物衰老的标志，并受到生活方式的影响。预计这项工作将证明昼夜节律未对准的临床意义对于数百万参与轮班工作的人，并提出新的策略来提高转变工作的容忍度。 公共卫生相关性：近20％的美国劳动人口从事转变工作，这种状况与患心血管疾病和糖尿病的风险增加有关。该项目的总体目标是定义昼夜节律失去率在升高的转移工作风险中的各自的作用。