Misalignment between circadian preference and accelerometer-derived actual sleep-wake cycle is associated with increased risk of cardiometabolic diseases: a prospective cohort study in UK Biobank

Background: Evidence has linked several circadian disruption indicators to adverse health outcomes, however, associations of misalignment between circadian preference and actual sleep-wake cycle with cardiometabolic diseases (CMDs) remains unclear. We aimed to prospectively investigate the associations of the circadian misalignment with CMDs including type 2 diabetes (T2D), chronic heart diseases (CHD), and stroke, and to uncover potential mechanisms linking circadian misalignment and CMDs. Methods: A total of 60,965 participants from the UK Biobank study without baseline CMDs and followed-up for an average of 7.9 years were included in the current analysis. Circadian misalignment was defined as discrepancies between self-reported chronotype and accelerometer-derived midpoint of sleep. Incident CMDs were derived from multiple medical source of data. Cox proportional hazards regression models were used to compute the hazard ratio (HR) and confidence intervals (CIs) on the association between circadian misalignment and incident CMDs. Results: U-shaped associations were found of the circadian misalignment with incident T2D and CHD after adjusting the potential confounders. Compared to individuals with aligned midsleep and circadian preferences, those with advanced and delayed circadian misalignment had higher risks of T2D [HRs (95%CI)s 1.22 (1.03, 1.45) and 1.39 (1.18, 1.62)]. However, only delayed circadian misalignment was significantly associated with an increased risk of CHD [HR (95%CI) 1.16 (1.02, 1.33)]. Liver function, lipid and glucose metabolism, and inflammatory markers partially explained the observed circadian misalignment and CMDs association (mediation proportion 12.3-44.6% for T2D, 8.8-20.5% for CHD). Additionally, early chronotype [HR (95%CI): 1.19 (1.06, 1.34)] rather than late chronotype was associated with an increased risk of incident T2D. Conclusion: Both advanced and delayed circadian misalignment were associated with increased risks of CMDs, suggesting potential benefits of aligning actual sleep-wake cycles with individual circadian preferences.