Saturday, May 4, 2024
5/4/2024
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.
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