Misalignment Between Circadian Preference and Accelerometer-Derived Sleep-Wake Cycle With Increased Risk of Cardiometabolic Diseases

Background: The relationship of circadian misalignment, sleep-wake cycle, and cardiometabolic diseases (CMDs) remains unclear. Objectives: This prospective study investigated the associations between circadian misalignment and CMDs, including type 2 diabetes (T2D), coronary heart disease (CHD), and stroke, and explored potential mechanisms. Methods: Data from 60,965 participants without pre-existing CMDs from the UK Biobank study and followed for an average of 7.9 years were analyzed. Circadian misalignment was determined by comparing self-reported chronotype and accelerometer-derived sleep timing. Incident CMDs were documented via multiple medical registries and self-reported information. Cox proportional hazards models were applied to estimate HRs and 95% CIs for these associations. Results: A U-shaped relationship between circadian misalignment and both T2D and CHD was observed. Compared to individuals with aligned midsleep and circadian preferences (the third quintile, Q3), those with advanced and delayed circadian misalignment had higher risks of T2D (HR: 1.22 [95% CI: 1.03-1.45] for Q1 and 1.39 [95% CI: 1.18-1.62] for Q5). Delayed circadian misalignment also associated with higher CHD risk (HR: 1.15 [95% CI: 1.01-1.31] for Q4 and 1.16 [95% CI: 1.02-1.33] for Q5). The association between delayed circadian misalignment and CMDs was greater in women (T2D, P_interaction = 0.03) and younger adults (CHD, P_interaction = 0.02). Early (HR: 1.19 [95% CI: 1.06-1.34]), rather than late, chronotype was associated with an increased T2D risk. Conclusions: Both advanced and delayed circadian misalignment were associated with an increased CMD risk, highlighting the potential health benefits of aligning sleep-wake cycles with individual circadian preferences.