LAUSR

Although insufficient sleep is a known risk factor for metabolic syndrome (MetS), the circadian timing of sleep is also involved in cardiac and metabolic regulation. As a result, circadian misalignment of the sleep-wake cycle, which is highly prevalent in adolescents, may independently impact the burden of MetS in youth. We analyzed data from 277 population-based randomly-selected adolescents from the Penn State Child Cohort (median 16 years; 47% female; 21% racial/ethnic minority) who had at least 5 nights of at-home actigraphy (ACT), an in-lab 9-h polysomnography (PSG) and an in-lab dual-energy X-ray absorptiometry (DEXA) scan. Two ACT-measured metrics of circadian misalignment were examined as effect modifiers: sleep midpoint (SM), the intra-individual mean midpoint of the sleep period, and sleep regularity (SR), the intra-individual standard deviation of sleep midpoint. DEXA-measured visceral adipose tissue (VAT) was the primary predictor. A continuous MetS score (i.e., sum of the age and sex adjusted z-scores of waist circumference, blood pressure, HOMA-IR, triglycerides, and HDL cholesterol) was the primary outcome. Linear regression models tested SM and SR as effect modifiers of the association of VAT with MetS, while accounting for sex, race/ethnicity, age, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index. A significant interaction was found between VAT and SR on MetS (p-interaction=0.05), while not between VAT and SM (p-interaction=0.15). Among adolescents with high sleep irregularity (≥ 45 minutes; n=164), each standard deviation increase in VAT was associated with 2.4 (0.2) standard deviations increase in MetS (p< 0.01), while this association was weaker among adolescents with low sleep irregularity [< 45 minutes; n=113; β=1.7 (0.3), p< 0.01]. An irregular circadian timing of sleep may further increase the impact of visceral adiposity on MetS burden in adolescents. Sleep irregularity, independent of sleep apnea and insufficient sleep, may contribute to the development of cardiometabolic sequelae associated with central obesity. National Institutes of Health (R01HL136587, UL1TR000127) and American Heart Association (23PRE1011962)