The role of irregular sleep schedules as a ubiquitous marker of chronic circadian disruption in cardiometabolic disease development

不规则的睡眠时间表作为心脏代谢疾病发展中慢性昼夜节律紊乱的普遍标志物的作用

• 批准号: 10664954
• 负责人: Tianyi Huang
• 金额: $ 74.83万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10664954
• 关键词: Accelerometer; Accounting; Age; Arginine; Attenuated; Awareness; Biological; Biological Process; Blood; Blood Pressure; Cardiometabolic Disease; Cardiovascular Diseases; Cardiovascular Physiology; Chronic; Circadian Dysregulation; Circadian Rhythms; Collection; Data; Data Collection; Development; Diabetes Mellitus; Disparity; Dose; Eating; Epidemiology; Ethnic Origin; Ethnic Population; European; Exhibits; Exposure to; Fostering; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genomics; Health; Health Promotion; Human; Hypertension; Incidence; Individual; Intervention; Link; Measures; Mediating; Metabolic; Metabolic syndrome; Multi-Ethnic Study of Atherosclerosis; Nobel Prize; Nurses; Nurses' Health Study; Obesity; Occupational; Omega-3 Fatty Acids; Outcome; Ownership; Participant; Pathogenicity; Pathway interactions; Pattern; Phenotype; Plasma; Population; Prevalence; Prevention; Public Health; Race; Recommendation; Reduce health disparities; Reproducibility; Research; Research Design; Risk; Risk Factors; Role; Rotation; Sample Size; Sampling; Schedule; Sleep; Sleep Disorders; Sleep disturbances; Sleeplessness; Source; Subgroup; Symptoms; Techniques; Translating; Tyrosine; Variant; Woman; Work; actigraphy; biobank; cardiometabolism; child bearing; circadian; cohort; digital; disorder prevention; disorder risk; epidemiology study; ethnic minority; experience; fitbit; handheld mobile device; heart rate variability; improved; innovation; linoleates; low socioeconomic status; metabolic profile; metabolomics; modifiable risk; novel; obesity risk; population based; prospective; racial minority; racial population; response; sex; shift work; sociodemographic factors; sociodemographics; trait; translational progress

Abstract Although circadian rhythms are established as a fundamental mechanism in various biologic processes, including metabolic and cardiovascular functioning, less is known regarding how disruption of circadian rhythms may contribute to development of cardiometabolic disease in broader human populations. Prior epidemiologic studies have predominantly focused on specific populations who experience extreme circadian disruption, such as rotating night shift workers. In this application, we will consider irregular sleep schedules as a ubiquitous marker of chronic circadian disruption and evaluate its role in cardiometabolic disease development. First, we will leverage the wealth of data from the UK Biobank (UKB), which has measured habitual sleep using accelerometer among 92,644 participants. We will characterize the dose-response relationships of irregular sleep schedules with risk of hypertension, diabetes and cardiovascular disease and identify potential threshold to define what level of sleep variability may be cardiometabolically unhealthy. We will also evaluate whether the observed associations differed by sociodemographic factors (e.g., age, sex, race/ethnicity) or other sleep traits (e.g., average sleep duration and insomnia symptoms). Further, given that sleep regularity represents a highly modifiable risk factor, we will evaluate whether regular sleep schedules may counteract genetic predisposition to cardiometabolic disease. Second, in the Nurses’ Health Study 3 (NHS3), we propose to measure habitual sleep using Fitbit and plasma metabolomics among 1,000 nurses, encompassing a wide range of variations in sleep schedules (including a random subset with night shift work). We hypothesize that irregular sleep schedules are associated with altered metabolites exhibiting circadian rhythms, such as omega-3 fatty acids, linoleate, arginine and tyrosine. We further hypothesize that this metabolic profile mediates the associations between irregular sleep and cardiometabolic traits including obesity, blood pressure and heart rate variability. In addition, we will collect new data on several emerging risk factors for irregular sleep that have not been examined in previous work, including mobile device use, late eating, breakfast skipping, pet ownership and childbearing/rearing in women. To increase rigor, reproducibility and generalizability, we will confirm our primary findings from UKB and NHS3 in the diverse Multi-Ethnic Study of Atherosclerosis (n=2,156), which have existing data on objectively measured habitual sleep, genomics, metabolomics and conventional epidemiologic risk factors. Overall, this project will provide larger-scale, more diverse and more in-depth evidence for the cardiometabolic impact of irregular sleep schedules in US and European populations, elucidate underlying biologic mechanisms, and ultimately foster development of potential public health recommendations and interventions to reduce irregular sleep and improve cardiometabolic health.

抽象的 尽管昼夜节律被确立为各种生物过程的基本机制， 包括代谢和心血管功能，但对于昼夜节律如何被破坏知之甚少 节律可能会导致更广泛人群中心脏代谢疾病的发生。 流行病学研究主要集中于经历极端昼夜节律的特定人群 干扰，例如轮班夜班工人 在本应用中，我们将不规则的睡眠时间表视为。 慢性昼夜节律紊乱的普遍标志物，并评估其在心脏代谢疾病中的作用 首先，我们将利用英国生物银行（UKB）测量的丰富数据。 我们将使用加速度计对 92,644 名参与者的习惯性睡眠进行表征。 不规律的睡眠时间与高血压、糖尿病和心血管疾病的风险之间的关系 确定潜在的阈值来定义什么水平的睡眠变异性可能对心脏代谢不健康。 还将评估观察到的关联是否因社会人口因素（例如年龄、性别、 种族/民族）或其他睡眠特征（例如，平均睡眠时间和失眠症状）。 睡眠规律是一个高度可改变的风险因素，我们将评估是否规律的睡眠时间表 其次，在护士健康研究 3 中。 (NHS3)，我们建议使用 Fitbit 和血浆代谢组学测量 1,000 名护士的习惯性睡眠， 涵盖睡眠时间表的各种变化（包括夜班工作的随机子集）。 我们发现，不规律的睡眠时间与表现出昼夜节律的代谢物有关 我们进一步研究了omega-3脂肪酸、亚油酸、精氨酸和酪氨酸。 代谢特征介导不规则睡眠与心脏代谢特征之间的关联，包括 此外，我们还将收集有关几种新兴风险的新数据。 之前的工作中没有研究过的睡眠不规律的因素，包括移动设备的使用、迟到 饮食、不吃早餐、饲养宠物和女性生育/抚养 提高严谨性和可重复性。 和普遍性，我们将在多元化的多种族研究中确认 UKB 和 NHS3 的主要发现 动脉粥样硬化 (n=2,156)，其中有客观测量的习惯性睡眠、基因组学、 总体而言，该项目将提供更大规模、更多的代谢组学和常规流行病学危险因素。 关于美国和美国不规则睡眠时间表对心脏代谢影响的多样化和更深入的证据 欧洲人口，阐明潜在的生物机制，并最终促进发展 潜在的公共卫生建议和干预措施，以减少不规律的睡眠并改善 心脏代谢健康。