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

Xianhui Ran,1,* Zhiyuan Fan,1,* Na Wang,1,* Tianyi Zhao,1 Hui Li,1 Xiao Liu,2 Enying Gong,3 Shuanghua Xie,4 Beiyao Gao,5 Lan An,6 Gang Chen,1 Xiao Ma,1,7 Chen Wang3,7 1Health Checkup Center, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Pharmacy, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 5Department of Rehabilitation Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 6Scientific Research Department, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 7State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao Ma, Email maxiaocjfh@163.comAim: 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: Among 123,791 participants (mean [SD] age, 41.3 [11.9] years; 50.8% male), 38,945 (31.5%) had metabolic multimorbidity. Prevalence was higher in men than in women (46.1% vs. 16.4%; P < 0.001). Age-related patterns differed by sex (P 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.Keywords: metabolic diseases, metabolic multimorbidity, cause-specific mortality, retrospective cohort