Yu Chengdong, Zhang Shuyuan, He Huijing, Wu Feitong, Lei Shaoyuan, Zong Xin'nan, Li Yuxiu, Zhang Huabing, Zhang Shuyang
Department of Growth and Development, Capital Institute of Pediatrics, Beijing, China.
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Int J Surg. 2025 Aug 1;111(8):5215-5227. doi: 10.1097/JS9.0000000000002552. Epub 2025 Jun 4.
The aim of this study was to investigate the longitudinal associations between the body size trajectory and the cardio-renal-metabolic (CRM) conditions in adulthood, and evaluate the joint association between body size trajectory and polygenic risk scores (PRS) of CRM conditions.
This prospective cohort study included 441 470 UK Biobank participants aged 40 to 70 years, recruited between March 2006 and July 2010. CRM conditions were defined as the occurrence of any of cardiovascular disease (CVD), chronic kidney disease (CKD), and type 2 diabetes (T2D). Cox regression models and Fine-Gray sub-distribution hazard models were used to estimate associations and competing risks of mortality. Mediation analysis and group-based trajectory modeling were performed to assess mediation effects and body size change trajectories. Additionally, interaction analyses were conducted to examine the combined effects of between the body size trajectories and PRS on CRM conditions.
The incidence density of CRM conditions was 128.9 per 1000 person-years. Adulthood overweight/obesity mediated the association between childhood plumper body size and CRM conditions (mediation proportion = 55.82%, P < 0.0001). Five trajectories of body size from birth to adulthood were identified, and the other four trajectories differing from the "normal-average-normal" trajectory were associated with increased risks of CRM conditions, with hazard ratio (HR) and 95% confidence interval (CI) ranging from 1.20 (1.15, 1.26) to 1.32 (1.28, 1.37). Intermediate and high genetic risk groups demonstrated elevated risks of CVD, CKD, and T2D, and the additive interactions were found between body size trajectories and PRS on CKD and T2D.
Maintaining a normal body size across the life cycle, even with intermediate or high genetic risk, may help mitigate the impact of genetic risk. Early monitoring and interventions aimed at sustaining a normal body size throughout life could provide life-course benefits in preventing CRM conditions, particularly for individuals with elevated genetic risk.
本研究旨在调查成年期身体大小轨迹与心肾代谢（CRM）状况之间的纵向关联，并评估身体大小轨迹与CRM状况的多基因风险评分（PRS）之间的联合关联。
这项前瞻性队列研究纳入了2006年3月至2010年7月招募的441470名年龄在40至70岁之间的英国生物银行参与者。CRM状况定义为发生任何心血管疾病（CVD）、慢性肾病（CKD）和2型糖尿病（T2D）。使用Cox回归模型和Fine-Gray子分布风险模型来估计关联和死亡的竞争风险。进行中介分析和基于群体的轨迹建模以评估中介效应和身体大小变化轨迹。此外，进行交互分析以检查身体大小轨迹和PRS对CRM状况的联合效应。
CRM状况的发病密度为每1000人年128.9例。成年期超重/肥胖介导了儿童期较胖身体大小与CRM状况之间的关联（中介比例=55.82%，P<0.0001）。确定了从出生到成年的五条身体大小轨迹，与“正常-平均-正常”轨迹不同的其他四条轨迹与CRM状况风险增加相关，风险比（HR）和95%置信区间（CI）为1.20（1.15，1.26）至1.32（1.28，1.37）。中高遗传风险组表现出CVD、CKD和T2D风险升高，并且在身体大小轨迹和PRS对CKD和T2D的影响上发现了相加交互作用。
即使具有中等或高遗传风险，在整个生命周期中保持正常身体大小可能有助于减轻遗传风险的影响。旨在终生维持正常身体大小的早期监测和干预措施可能在预防CRM状况方面提供终生益处，特别是对于遗传风险升高的个体。
