Metabolic Multimorbidity and Risk of All-Cause and Cause-Specific Mortality: A Retrospective Cohort Study of 123,791 Chinese Adults

Aim: Metabolic diseases are increasingly prevalent worldwide and often coexist. However, the patterns of metabolic multimorbidity and their long-term associations with mortality remain poorly understood. This study aimed to characterize these patterns and evaluate their associations with all-cause and cause-specific mortality. Methods: This retrospective cohort study included 123,791 adults aged 25-74 years who underwent health examinations at a large medical center in northern China between 2015 and 2022. Five metabolic diseases were assessed: diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease, and obesity. Metabolic multimorbidity was defined as the coexistence of two or more of these conditions. Cox proportional hazards models were used to estimate associations with all-cause, cardiovascular, and cancer mortality. Results: for interaction <0.001), with men showing a higher burden at younger ages and women showing a marked rise after midlife. During a median follow-up of 6.1 years (IQR, 4.2-7.6), 724 deaths (0.6%) occurred. Increasing numbers of coexisting diseases were associated with progressively higher risks of all-cause mortality (adjusted hazard ratios [aHRs], 1.38 [95% CI, 1.09-1.76] for one disease to 2.92 [1.82-4.68] for five diseases vs none; P for trend <0.001), cardiovascular mortality (aHRs, 1.78 [1.06-2.99] to 5.13 [2.25-11.7]; P for trend <0.001), and cancer mortality (aHRs, 1.36 [0.91-2.03] to 3.84 [1.90-7.78]; P for trend <0.001). Conclusion: Metabolic multimorbidity was highly prevalent and exhibited distinct age- and sex-related patterns, with a graded association with mortality risk. These findings may reflect shared pathophysiological mechanisms and support integrated, sex-specific strategies to mitigate the growing metabolic burden.