Circadian disruption and cardiometabolic risk during the transition from adolescence to young adulthood

/ABSTRACT The transition from adolescence to young adulthood is a period marked by multiple physical and behavioral changes that could impact long-term cardiometabolic disease risk. Changes in circadian rhythm are a normal part of the pubertal transition but at the extreme may result in circadian disruption, which is the non-optimal biological timing of sleep, eating, physical activity, or irregularity in their timing. Emerging evidence suggests that circadian disruption is linked to poor cardiometabolic health, potentially through alteration of circadian gene regulation. Further, the literature and preliminary evidence suggests that relationships of circadian disruption and cardiometabolic health are nuanced and may depend on important effect modifiers including sex, chronotype, and sleep disordered breathing (SDB). Specifically, females and individuals with late chronotypes (a genetically- driven preference for late sleep/wake behaviors) may be more likely to experience poor cardiometabolic health in response to circadian disruption. Additionally, SDB is a known risk factor for adverse cardiometabolic health, and our preliminary cross-sectional evidence suggests it is an effect modifier of the relationship between circadian disruption and high blood pressure. Building upon this strong foundation of prior knowledge and preliminary evidence, the present grant is designed to test the central hypothesis that persistent circadian disruption, including misaligned sleep, eating, and activity timing, will be related to development of cardiometabolic risk from adolescence to young adulthood through epigenetic alterations of circadian genes and will be modified by sex, chronotype, and SDB. To do this, we will leverage existing objectively-assessed sleep/wake patterns and cardiometabolic health biomarkers collected in >500 participants twice during peri- puberty (ages 14.5 and 16.5). In Aim 1, we will conduct a follow-up visit during young adulthood (age 26, YA1) to test the hypothesis that persistent circadian disruption from adolescence to young adulthood will be related to development of metabolic syndrome (MetS). In Aim 2, we will explore epigenetic regulation of important circadian and metabolic genes as a plausible mechanism linking circadian disruption with risk of developing MetS. Both of these aims will consider possible effect modification by chronotype and sex. Finally, in Aim 3, we will conduct home sleep apnea tests in the YA1 visit as an objective measure of SDB and subsequently evaluate whether SDB is an effect modifier of circadian disruption and cardiometabolic health relationships during young adulthood. Overall, the completion of these aims will yield novel insights into the underexplored longitudinal links between circadian disruption and cardiometabolic health and will bring circadian health-related behaviors to the forefront as important preventative measures against adverse cardiometabolic health during adolescence and young adulthood. Project Number: 1R01HL169893-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Erica Jansen | Institution: UNIVERSITY OF MICHIGAN AT ANN ARBOR, ANN ARBOR, MI | Award Amount: $691,124 | Activity Code: R01 | Study Section: Lifestyle and Health Behaviors Study Section[LHB] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HL16989301A1