Wang Jiacheng, Zheng Yi, Jiang Yanfeng, Suo Chen, Zhang Tiejun, Chen Xingdong, Xu Kelin
School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China.
State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.
Prev Med. 2025 Feb;191:108211. doi: 10.1016/j.ypmed.2024.108211. Epub 2024 Dec 19.
Physical activity has protective effects on cardiometabolic diseases (CMDs), but the role of metabolism related to physical activity in this process is unclear.
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.
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]).
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.
体育活动对心脏代谢疾病（CMDs）具有保护作用，但体育活动相关的代谢在这一过程中的作用尚不清楚。
在2006年至2022年英国生物银行开展的前瞻性队列研究中，纳入基线时无CMDs的参与者（n = 73,990）。我们识别出与体育活动相关的代谢物，并使用线性回归和弹性网络回归构建代谢特征。采用Cox分析和中介分析探讨体育活动、代谢特征与CMDs（2型糖尿病 [T2D]、冠心病 [CHD] 和中风）之间的关联。通过相加风险模型和交互作用所致相对超额风险（RERI）评估代谢特征与遗传易感性（根据多基因风险评分中位数分为“低”和“高”）之间的相互作用。多状态模型评估代谢特征与疾病进展之间的关联。
我们发现58种代谢物与体育活动相关，其中17种用于构建代谢特征。该代谢特征与降低T2D（风险比 [HR] = 0.13[0.10 - 0.16]）、CHD（HR = 0.40[0.34 - 0.47]）和中风（HR = 0.67[0.53 - 0.86]）的风险相关，并介导了体育活动与T2D之间40.56%的关联。该代谢特征在T2D（RERI = 1.57[1.09 - 2.05]）和CHD（RERI = 0.27[0.05 - 0.49]）的遗传风险方面表现出相加交互作用。最后，该代谢特征与降低从CMD转变为CMM的风险相关（HR = 0.58[0.42 - 0.81]）。
体育活动相关的代谢特征与降低CMDs和CMM的风险相关。我们再次从代谢角度强调体育活动对预防CMDs的重要性，尤其是对于遗传风险高的个体。
