Circadian Syndrome Outperforms Metabolic Syndrome in Predicting Early Death: Study Shows
China: A new analysis of two large population cohorts published in Diabetes Research and Clinical Practice suggests that disruptions in the body's internal clock may be a more powerful predictor of death than traditional metabolic risk factors.
Researchers found that individuals with circadian syndrome (CircS)—a cluster of conditions reflecting misalignment of sleep–wake rhythms and metabolic health—had a 34–42 percent higher risk of all-cause mortality, compared with a 21–30 percent increase in those with metabolic syndrome (MetS). CircS was consistently associated with greater risks of death from cardiovascular disease, heart disease, stroke, and cancer, highlighting the potential importance of circadian factors in long-term health assessment.
The investigation, led by Dr. Da Pan of the Key Laboratory of Environmental Medicine and Engineering and the Department of Nutrition and Food Hygiene at Southeast University, Nanjing, China, drew on data from two extensive cohorts: the U.S. National Health and Nutrition Examination Survey (NHANES) and the UK Biobank. Together, these cohorts comprised nearly 420,000 participants, enabling the team to compare the predictive accuracy of MetS and CircS for mortality outcomes across various populations and age groups.
The key findings of the study were as follows:
- In fully adjusted analyses from the NHANES cohort, circadian syndrome (CircS) was associated with a 34% increase in all-cause mortality and a 65% increase in heart disease mortality, compared with metabolic syndrome (MetS), which was associated with a 21% and 56% increase in these risks, respectively.
- In the UK Biobank data, CircS was associated with higher mortality across several conditions, with hazard ratios (HRs) of 1.78 for heart disease, 1.24 for cancer, 1.66 for overall cardiovascular disease, 1.93 for ischemic heart disease, and 1.42 for stroke, exceeding the HRs for MetS (1.68, 1.19, 1.56, 1.81, and 1.36, respectively).
- All-cause mortality in the UK Biobank cohort increased by 42% for CircS and 30% for MetS.
- The strongest associations between CircS and mortality were observed in middle-aged adults, while the effect diminished in individuals aged 70 years or older.
- Predictive models that included CircS provided better risk prediction than those based only on MetS, as shown by improved Akaike and Bayesian information criteria scores.
Dr. Pan and colleagues note that CircS captures a broader range of physiological and behavioral factors—such as sleep disturbances, sedentary lifestyle, and stress—that increasingly characterize modern life. They argue that including circadian-related indicators alongside conventional metabolic measures could refine risk stratification and prevention strategies for major chronic diseases.
While further research is needed to clarify the biological pathways and to test clinical applications, the findings point toward circadian health as an emerging frontier in preventive medicine. Integrating circadian assessments into routine care, the authors conclude, may enhance the ability to identify individuals at greatest risk of premature death and guide more personalized interventions.
Reference:
Pan, D., Wang, Y., Zhang, C., Lu, Y., Yin, S., Wang, P., Xia, J., Yu, J., Gao, H., Sun, G., & Xu, D. (2025). Do circadian factors improve mortality risk prediction? A dual-cohort analysis of metabolic and circadian syndromes. Diabetes Research and Clinical Practice, 112919. https://doi.org/10.1016/j.diabres.2025.112919
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