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

项目摘要 尽管公众意识有所提高，但在我们的国家，自愿减少睡眠仍然普遍存在。 社会目前，超过三分之一的美国成年人报告大多数晚上睡眠时间为6小时或更少。这是 问题是，短睡眠时间会导致心血管（CV）风险高，从而导致CV增加 疾病和死亡率。增加睡眠时间可以减轻代谢障碍，但替代策略， 减少习惯性短睡眠者的心脏代谢风险。这一点在增加 睡眠持续时间不成功。不幸的是，短睡眠者的新陈代谢机制 还没有完全被理解。这阻碍了CV预防替代策略的开发。近几 多年来，昼夜节律系统在维持健康代谢中的重要性被认识到。昼夜 该系统协调基本生理和行为功能的24小时周期性，因此代表了一种 体内平衡的基本组成部分相反地，内源性血管的扁平化和/或错位 禁食/进食行为的昼夜节律（褪黑激素分泌）可能会导致代谢功能障碍，例如 高血压（BP）和胰岛素抵抗（IR）。在短睡眠者中，夜间暴露在人造光下， 延长进食时间可减少和延迟褪黑激素分泌。然而，没有任何研究检查了 饮食持续时间的昼夜节律和代谢影响。我们假设大吃大喝 持续时间通过改变褪黑激素分泌而导致习惯性短睡眠者的高血压和IR。 因此，时间限制饮食（TRE）将通过增加和调整褪黑激素来降低血压和IR 禁食/进食的分泌。事实上，几项TRE临床试验显示参与者的CV风险降低 肥胖症，糖尿病前期，代谢综合征有趣的是，最近的一项研究表明， 昼夜节律失调的后果可能是由于空腹/进食与内源性 昼夜节律支持我们假设的是这些先前的研究和初步数据， TRE降低短睡眠者的BP和IR。我们将通过进行一个随机的，平行的 在确认习惯性短睡眠（≤ 6.5小时/夜）和进食窗口> 14小时/天的参与者中进行的手臂研究， 患者设置。参与者（n=100，年龄18- 45岁; BMI 25- 35 kg/m2）将在研究期间接受为期4周的干预。 他们将被随机分配到习惯性进食时间（> 14小时/天，对照）或缩短进食时间 (TRE，8h/天）。动态24小时血压（目标1）、葡萄糖代谢（混合餐耐量试验，目标2），以及 将在基线、干预中期和干预结束时评估褪黑激素昼夜节律（目标3）， 见解.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 葡萄糖、体力活动、睡眠时间和光照。我们的研究提供了机械的见解， 短睡眠者的昼夜节律失调和TRE的相应有益作用。临床翻译 该研究的影响在于确定TRE作为抵消短睡眠者CV风险的替代策略。

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.