0199 Circadian Misalignment, Cardiac-Autonomic and Inflammatory Pathways, and Metabolic Syndrome in Adolescents

Abstract Introduction Although insufficient sleep is a known risk factor for metabolic syndrome (MetS), circadian misalignment, which is highly prevalent during adolescence, may also impact cardiac, autonomic and immune regulation. Prior studies have shown that circadian misalignment impacts the association between visceral adiposity (VAT) and MetS in youth, which is not explained by lifestyle factors such as diet or physical activity. We hypothesize that cardiac-autonomic and inflammatory pathways will significantly diminish the impact of circadian misalignment on the relationship between VAT and MetS in adolescents. Methods We analyzed 262 adolescents from the Penn State Child Cohort (median 16y; 48% female; 22% racial/ethnic minority) who had at least 5 nights of actigraphy (ACT) and were evaluated while in-school (n=171) or on-break (n=91). They also had 9-h polysomnography (PSG), a dual-energy X-ray absorptiometry (DXA) scan, 24-h Holter-monitoring heart rate variability (HRV), and a composite score of inflammatory biomarkers, including fasting C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), adiponectin, and leptin data. DXA-measured VAT was the predictor. A continuous MetS score was the outcome. ACT-measured sleep midpoint (SM), sleep irregularity (SI), and social jetlag (SJL) were tested as effect modifiers. Linear regression models were first adjusted for essential covariates (i.e., sex, race/ethnicity, age, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index), and, thereafter, for HRV and inflammatory biomarkers. Results Significant interactions were found between VAT and SM, SI or SJL while in-school on MetS adjusting for essential covariates (interaction effects: 0.58 (0.25) p=0.023, 0.38 (0.15) p=0.013, and 0.69 (0.22) p=0.002, respectively). Further adjusting for 24-HRV indices (e.g., Log-HF and RMSSD) or for inflammatory biomarkers did not significantly impact the effect modifications observed (e.g., interaction effects after adjusting for 24-h Log-HF: 0.55 (0.25) p=0.028, 0.36 (0.15) p=0.018, and 0.67 (0.21) p=0.002, respectively). Conclusion Cardiac-autonomic or inflammatory pathways do not significantly account for the role that circadian misalignment has in increasing the impact of VAT on MetS burden in adolescents. Other pathways, specific to circadian rhythms either biological or behavioral, may be involved in how circadian misalignment contributes to the development of cardiometabolic sequelae associated with central obesity. Support (if any) AHA (23PRE1011962), NIH (R01HL136587,R01MH118308,UL1TR000127)