Cardiovascular risk and circadian misalignment in short sleepers- role of extended eating period.

短睡眠者的心血管风险和昼夜节律失调——延长进食时间的作用。

• 批准号: 10733844
• 负责人: Prachi Singh
• 金额: $ 74.9万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733844
• 关键词: Adult; Age; Ambulatory Blood Pressure Monitoring; Attenuated; Awareness; Behavior; Behavioral; Blood Pressure; Body mass index; Cardiovascular Diseases; Cardiovascular system; Circadian Dysregulation; Circadian Rhythms; Circadian desynchrony; Clinical; Clinical Trials; Continuous Glucose Monitor; Data; Development; Diurnal Rhythm; Eating; Ensure; Exposure to; Fasting; Feeding Patterns; Feeding behaviors; Glucose; Health; High Prevalence; Homeostasis; Hour; Hypertension; Impairment; Insulin; Insulin Resistance; Intervention; Life Style Modification; Light; Mediating; Melatonin; Metabolic; Metabolic dysfunction; Metabolic syndrome; Metabolism; Molecular; Obesity; Outpatients; Participant; Periodicity; Physical activity; Physiological; Physiological Processes; Population; Prediabetes syndrome; Prevention; Prevention strategy; Protocols documentation; Randomized; Reporting; Research; Risk; Risk Reduction; Role; Safety; Sleep; Societies; System; Testing; Time; Time-restricted feeding; United States National Institutes of Health; arm; blood glucose regulation; blood pressure elevation; blood pressure reduction; cardiometabolic risk; cardiovascular risk factor; circadian; clinical implementation; clinical translation; feeding; glucose metabolism; improved; innovation; insight; insulin sensitivity; lifestyle factors; mortality; novel; obese person; pressure; primary outcome; response; translational impact; volunteer

PROJECT SUMMARY In spite of increased public awareness, voluntary sleep curtailment remains prevalent and pervasive in our society. Currently, more than one-third of the US adult population report sleeping 6h or less most nights. This is problematic as short sleep duration contributes to high cardiovascular (CV) risk and consequent increased CV disease and mortality. Increasing sleep duration mitigates the metabolic impairment, but alternate strategies to reduce cardiometabolic risk in habitual short sleepers are lacking. This is especially important when increasing sleep duration is unsuccessful. Unfortunately, the mechanisms underlying metabolic detriments in short sleepers are not completely understood. This hinders the development of alternate strategies for CV prevention. In recent years, the importance of circadian system in maintaining a healthy metabolism is recognized. The circadian system coordinates 24h periodicity in essential physiological and behavioural function and thus represents a fundamental component of homeostasis. Conversely, flattening and/or misalignment of the endogenous circadian rhythms (melatonin secretion) with fasting/feeding behaviour can cause metabolic dysfunction such as high blood pressure (BP) and insulin resistance (IR). In short sleepers, nighttime exposure to artificial light and extended eating duration may decrease and delay melatonin secretion. However, no study has examined the circadian and metabolic effects of eating duration in this population. We hypothesize that extended eating duration contributes to high BP and IR in habitual short sleepers via altered melatonin secretion. Therefore, time restricted eating (TRE) will lower BP and IR by increasing and aligning melatonin secretion to fasting/feeding. Indeed, several TRE clinical trials have shown CV risk reduction in participants with obesity, pre-diabetes, and metabolic syndrome. Interestingly, a recent study suggested that metabolic consequences of circadian misalignment likely results from misalignment of fasting/feeding with endogenous circadian rhythm. Support for our hypothesis comes from these prior studies and preliminary data showing that TRE reduces BP and IR in short sleepers. We will test our hypothesis by conducting an randomized, parallel arm study in participants with confirmed habitual short sleep (≤6.5h/night) and eating window of >14h/day in out- patient settings. Participants (n=100, age 18-45y; BMI 25-35kg/m2) will undergo a 4-week intervention during which they will be randomly assigned to habitual eating duration (>14h/day, control) or shortened eating duration (TRE, 8h/day). Ambulatory 24h hour BP (Aim 1), glucose metabolism (mixed-meal tolerance test, Aim 2), and melatonin diurnal rhythm (Aim 3) will be assessed at baseline, mid- and end- intervention to gain temporal insights. To ensure compliance with assigned eating duration and study protocol, we will continuously monitor glucose, physical activity, sleep duration, and light exposure. Our study provides mechanistic insights into circadian dysregulation in short sleepers and corresponding beneficial effects of TRE. The clinical translational impact of the study is in the identification of TRE as an alternate strategy to offset CV risk in short sleepers.

项目总结 尽管公众意识增强了，但自愿减少睡眠仍然普遍存在，在我们的 社会。目前，超过三分之一的美国成年人口报告称，大多数晚上的睡眠时间不超过6小时。这是 睡眠时间短会增加心血管(CV)风险，从而导致CV增加，这是有问题的 疾病和死亡率。增加睡眠时间可以缓解代谢损伤，但替代策略是 减少习惯性短睡眠者的心脏代谢风险。这在增加 睡眠持续时间不成功。不幸的是，短睡者代谢损害的潜在机制 还没有完全被理解。这阻碍了预防心血管疾病的替代战略的发展。在最近 多年来，人们认识到昼夜节律系统在维持健康新陈代谢方面的重要性。昼夜节律 系统协调基本生理和行为功能的24小时周期性，因此代表着 动态平衡的基本组成部分。相反，内源的扁平化和/或错位 具有禁食/进食行为的昼夜节律(褪黑激素分泌)可导致代谢功能障碍，如 高血压(BP)和胰岛素抵抗(IR)。在短睡者中，夜间暴露于人造光和 长时间进食可能会减少和延缓褪黑激素的分泌。然而，还没有研究检查过 进食时间对该人群昼夜节律和代谢的影响。我们假设延长进食时间 持续时间通过改变褪黑激素的分泌导致习惯性短睡眠者的高血压和高胰岛素抵抗。 因此，限时进食可通过增加和调整褪黑激素来降低血压和胰岛素抵抗 从分泌到禁食/喂食。事实上，几项tre临床试验已经显示参与者的心血管风险降低。 患有肥胖症、糖尿病前期和代谢综合征。有趣的是，最近的一项研究表明，新陈代谢 昼夜节律失调的后果可能是禁食/进食与内源性失调所致 昼夜节律。我们的假设得到了这些先前的研究和初步数据的支持 TRE可降低短睡者的BP和IR。我们将通过进行随机的平行试验来检验我们的假设 对确认为习惯性短睡眠(≤6.5小时/晚)和外出进食时间窗为14小时/天的参与者进行ARM研究 患者设置。参与者(n=100，年龄18-45岁；体重指数25-35 kg/m2)将接受为期4周的干预 他们将被随机分配到习惯进食持续时间(14小时/天，对照组)或缩短进食持续时间 (Tre，8小时/天)。24小时动态血压(AIM 1)、糖代谢(混合餐耐量试验，AIM 2)； 褪黑激素的昼夜节律(目标3)将在基线、中期和末期干预时进行评估，以获得时间 洞察力。为了确保遵守指定的进食时间和研究方案，我们将持续监测 血糖、体力活动、睡眠时间和光照。我们的研究提供了对 短睡者的昼夜节律失调及tre的有益作用。临床翻译 这项研究的影响在于确定TRE是抵消短睡者心血管风险的替代策略。