Association between physical activity-related metabolic signature and cardiometabolic diseases and multimorbidity: A cohort study from UK biobank

Jiacheng Wang; Yi Zheng; Yanfeng Jiang; Chen Suo; Tiejun Zhang; Xingdong Chen; Kelin Xu

doi:10.1016/j.ypmed.2024.108211

Association between physical activity-related metabolic signature and cardiometabolic diseases and multimorbidity: A cohort study from UK biobank

Prev Med. 2024 Dec 19:191:108211. doi: 10.1016/j.ypmed.2024.108211. Online ahead of print.

Authors

Jiacheng Wang¹, Yi Zheng², Yanfeng Jiang³, Chen Suo⁴, Tiejun Zhang⁵, Xingdong Chen⁶, Kelin Xu⁷

Affiliations

¹ School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China.
² State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.
³ State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
⁴ School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
⁵ School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China; Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, China.
⁶ State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai, China; Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China; Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, China. Electronic address: xingdongchen@fudan.edu.cn.
⁷ School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China. Electronic address: xukelin@fudan.edu.cn.

PMID: 39708996
DOI: 10.1016/j.ypmed.2024.108211

Abstract

Objective: Physical activity has protective effects on cardiometabolic diseases (CMDs), but the role of metabolism related to physical activity in this process is unclear.

Methods: In the prospective cohort study from UK Biobank between 2006 and 2022, participants free of CMDs at baseline were included (n = 73,990). We identified physical activity-related metabolites and constructed metabolic signature using linear regression and elastic net regression. Association between physical activity, metabolic signature, and CMDs (type 2 diabetes [T2D], coronary heart disease [CHD], and stroke) were explored using Cox and mediation analyses. Interactions between the metabolic signature and genetic susceptibility (categorized into "low" and "high" based on the median of polygenic risk scores) were assessed by additive hazard models and relative excess risk due to interaction (RERI). Multi-state models evaluated the association between metabolic signature and disease progression.

Results: We found 58 metabolites were related to physical activity, of which 17 were used to construct metabolic signature. The metabolic signature was associated with reduced risk of T2D (HR = 0.13[0.10-0.16]), CHD (HR = 0.40[0.34-0.47]), and stroke (HR = 0.67[0.53-0.86]), and mediated 40.56 % of the association between physical activity and T2D. The metabolic signature exhibited additive interactions with genetic risk for T2D (RERI = 1.57[1.09-2.05]) and CHD (RERI = 0.27[0.05-0.49]). Finally, the metabolic signature was associated with a reduced risk of transition from CMD to CMM (HR = 0.58[0.42-0.81]).

Conclusion: Physical activity-related metabolic signature is linked to reduced risks of CMDs and CMM. We once again emphasize the importance of physical activity for CMDs prevention from a metabolic perspective, especially for individuals at high genetic risk.

Keywords: Cardiometabolic disease; Genetic susceptibility; Interaction; Metabolome; Multimorbidity.