Mechanisms underlying adverse health consequences of shift work

轮班工作对健康造成不良后果的机制

• 批准号: 7741471
• 负责人: FRANK A SCHEER
• 金额: $ 31.5万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7741471
• 关键词: Acute; Address; Adipocytes; American; Animals; Basal metabolic rate; Behavior; Behavioral; Biological; Biological Markers; Blood Pressure; Blood Vessels; CCL2 gene; Cardiovascular Diseases; Cardiovascular system; Catecholamines; Chronic; Circadian Rhythms; Commuting; Crossover Design; Data; Desire for food; Detection; Development; Diabetes Mellitus; Eating; Endocrine; Energy Intake; Energy Metabolism; Epidemiologic Studies; Epidemiology; Equilibrium; Exposure to; Fasting; Future; Glucose; Health; Heart; Hormonal; Hormones; Hour; Human; Hunger; Individual; Inflammation; Inflammatory; Insulin; Insulin Resistance; Interleukin-6; Intervention Studies; Laboratories; Lead; Leptin; Life; Life Style; Light; Link; Measurement; Measures; Metabolic; Modeling; Monitor; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Pacemakers; Peripheral; Phase; Physiological; Physiological Adaptation; Physiology; Plasma; Population; Predisposition; Pressoreceptors; Protocols documentation; Public Health; Randomized; Relative (related person); Reporting; Research; Risk; Risk Factors; Risk Marker; Satiation; Schedule; Simulate; Sleep; Sleep Wake Cycle; Solid; System; Temperature; Testing; Time; Tumor Necrosis Factor-alpha; Work; actigraphy; adiponectin; awake; cardiovascular risk factor; circadian pacemaker; clinically relevant; design; diabetes risk; energy balance; feeding; ghrelin; glucose metabolism; human TNF protein; increased appetite; inflammatory marker; insulin sensitivity; intravenous glucose tolerance test; light effects; light intensity; pressure; prevent; public health relevance; research study; resistin; response; shift work; suprachiasmatic nucleus

DESCRIPTION (provided by applicant): Epidemiological studies have shown that shift work is associated with an increased risk for the development of diabetes, obesity, and cardiovascular disease. Recent animal studies and acute human studies suggest that this association may be due to the misalignment between the fasting/feeding and sleep/wake cycles relative to the cycle of the endogenous circadian timing system. That is, activity and food intake during the 'biological night' or sleep loss during the 'biological day' may result in metabolic, autonomic and endocrine changes that pre-dispose to diabetes, obesity, and cardiovascular disease. For instance, we recently found that acute experimental misalignment between the sleep/wake and fasting/feeding cycle-typical of shift work-can lead to significantly decreased plasma leptin, increased plasma glucose and increased mean arterial pressure. We also found reduced sleep efficiency during circadian misalignment to an extent that has been shown to significantly decrease circulating leptin, increase appetite and increase sympatho-vagal balance in other acute studies. Building on these new findings, and overcoming a number of limitations in the prior work, we aim to determine the progressive physiological changes across a work week of realistic simulated shift work focusing on those metabolic, endocrine, inflammatory, and cardiovascular variables that are biomarkers of susceptibility to the development of diabetes, obesity, and cardiovascular disease. Also, since the effect of shift work is most clinically relevant in actual shift workers, we will determine whether the potential maladaptive physiological effects are observed also in chronic shift workers or that this population has adapted. We will use a 14 day/night laboratory protocol involving a within-subject, randomized, cross-over design including a simulated night shift and day shift schedule using a formal battery of scheduled behaviors and light exposures in healthy day workers and shift workers. The principal dependent variables are derived from circulating adipocyte hormones (leptin, adiponectin, resistin, ghrelin), measures of insulin resistance (mixed meal response and intravenous glucose tolerance test), inflammatory markers (CRP, IL-6, TNF-alpha, MCP-1), peripheral vascular endothelial function, and autonomic control (catecholamines, sympatho-vagal balance, baroreceptor sensitivity and systemic blood pressure). Changes in these variables will be monitored across numerous days and nights of shift work, compared between day and night shift schedules, and compared between non-shift workers and chronic shift workers. Following on from the convincing epidemiological studies and recent acute physiology studies, the proposed intense physiological study utilizing realistic shift work-schedules over a number of days are now needed to determine the specific underlying metabolic, endocrine, inflammatory, autonomic and cardiovascular mechanisms that explain the adverse health consequences of chronic shift work. We anticipate that this work will lay the groundwork for the development of targeted and timed therapies to counteract the public health burden of shift work. PUBLIC HEALTH RELEVANCE: Shift work is associated with an increased risk for diabetes, obesity, and cardiovascular disease. This research will determine whether simulated night work increases metabolic, hormonal, neuronal, heart and blood vessel risk factors in shift workers and non-shift workers. This research will provide a possible mechanistic explanation for the increased risk for diabetes, obesity, and cardiovascular disease in shift workers.

描述（由申请人提供）：流行病学研究表明，转移工作与糖尿病，肥胖和心血管疾病的发展风险增加有关。最近的动物研究和急性人类研究表明，这种关联可能是由于禁食/喂养与睡眠/尾流循环相对于内源性昼夜节律系统的周期而造成的。也就是说，在“生物之夜”期间的活动和食物摄入量或在“生物日”期间的睡眠损失可能会导致代谢，自主和内分泌变化，这些变化预先诊断为糖尿病，肥胖和心血管疾病。例如，我们最近发现睡眠/唤醒与禁食/喂养周期型在移位工作式启动型急性实验不对对准会导致血浆瘦素显着降低，血浆葡萄糖增加和平均动脉压增加。我们还发现，在其他急性研究中，昼夜节律未对准期间的睡眠效率降低了，该程度可显着降低循环瘦素，增加食欲并增加交感神经的平衡。在这些新发现的基础上，并克服了先前工作中的许多局限性，我们旨在确定在逼真的模拟轮班工作周中的渐进生理变化，重点是这些代谢，内分泌，炎症和心血管变量，这些变量是对糖尿病，糖尿病，肥胖症，肥胖症和心脏病性病的易感性生物标志物的生物标志物。同样，由于转移工作的影响在实际的班次工人中最相关，因此我们将确定在慢性转移工人中是否也观察到潜在的适应不良生理影响，或者该人群已经适应。我们将使用14天/夜间实验室协议，其中涉及受试者内，随机，交叉设计，包括模拟的夜班和一日游计划，并使用正式的计划行为和健康的日常工作人员和转变工人中的正式行为和轻型暴露。主要因变量是从循环脂肪细胞激素（瘦素，脂联素，抵抗素，生长素蛋白），胰岛素抵抗度（混合膳食反应和静脉葡萄糖耐受性测试），炎症标记，CRP，IL-6，TNF-ALPHA，PERIPRAIL EXTORTIL FASTICTAL，PASTIPRIAL EXTORTIAN，TNF-ALPHA和（儿茶酚胺，交感神经平衡，压力感受器敏感性和全身血压）。这些变量的变化将在白天和夜班时间表之间的多个白天和夜晚进行监控，并在非转移工人和慢性转移工人之间进行比较。从令人信服的流行病学研究和最新的急性生理学研究中，现在需要在许多天中使用现实的转变工作安排来确定特定的代谢，内分泌，自主性，自主性和心排血管机制来解释不良健康后果的不良健康后果。我们预计，这项工作将为开发有针对性和定时疗法的开发奠定基础，以抵消公共卫生的工作负担。公共卫生相关性：轮班工作与糖尿病，肥胖症和心血管疾病的风险增加有关。这项研究将确定模拟的夜间工作是否增加了转变工人和非迁移工人中的代谢，荷尔蒙，神经元，心脏和血管风险因素。这项研究将为轮班工人中糖尿病，肥胖和心血管疾病的风险增加提供可能的机械解释。