Jin Qianyun, Liu Siwen, Zhang Yunmeng, Ji Yuting, Wu Jie, Duan Hongyuan, Liu Xiaomin, Li Jingjing, Zhang Yacong, Lyu Zhangyan, Song Fangfang, Song Fengju, Li Hua, Huang Yubei
Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Key Laboratory of Prevention and Control of Human Major Diseases, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, China.
Department of Endoscopy, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Sci Rep. 2025 Jan 9;15(1):1472. doi: 10.1038/s41598-025-85519-9.
Severe obesity is often associated with inflammation and insulin resistance (IR), which expected to increase the risks of mortality and cancers. However, this relationship remains controversial, and it's unclear whether healthy lifestyles can mitigate these risks. The independent and joint associations of severe obesity (body mass index ≥ 35 m/kg), inflammation (C-reactive protein > 10 mg/L and systemic inflammation markers > 9th decile), and IR surrogates with the risks of all-cause mortality and all-site cancers, were evaluated in 163,008 participants from the UK Biobank cohort. Further analyses were conducted to investigate how these associations were modified by lifestyle. During a median follow-up of 11.0 years, we identified 8844 deaths and 20,944 cancer cases. Severe obesity, inflammation and IR were each independently associated with increased risks of all-cause mortality [HRs(95%CIs) 1.24(1.17-1.30), 1.63(1.55-1.72) and 1.11(1.05-1.17)] and all-site cancers [1.06(1.02-1.10), 1.14(1.10-1.19) and 1.02(0.99-1.06)]. Joint analyses revealed significantly elevated risks of all-cause mortality and all-site cancers due to interaction between severe obesity, inflammation and IR, with the highest HRs(95%CIs) of 1.88(1.67-2.11) and 1.20(1.08-1.34), respectively. Further analyses showed stronger interaction between severe obesity, inflammation, IR and lifestyles, with similar associations observed in both males and females. Additionally, compared with unfavorable lifestyles, favorable lifestyles attenuated the risks of both all-cause mortality [the highest HRs(95%CIs) 2.35(1.75-3.15) vs. 3.72(2.86-4.84) for favorable vs. unfavorable lifestyles] and all-site cancers [1.16(0.89-1.53) vs. 1.63(1.26-2.10)]. Severe obesity interacts with inflammation and IR to exacerbate the risks of all-cause mortality and all-site cancers. Nonetheless, adherence to healthy lifestyles is recommended to mitigate these increased risks.
重度肥胖通常与炎症和胰岛素抵抗（IR）相关，这可能会增加死亡和患癌风险。然而，这种关系仍存在争议，目前尚不清楚健康的生活方式是否能够降低这些风险。在英国生物银行队列的163,008名参与者中，评估了重度肥胖（体重指数≥35m/kg）、炎症（C反应蛋白>10mg/L和全身炎症标志物>第九十分位数）以及IR替代指标与全因死亡率和所有部位癌症风险的独立及联合关联。进一步分析旨在研究这些关联如何受到生活方式的影响。在中位随访11.0年期间，我们确定了8844例死亡和20944例癌症病例。重度肥胖、炎症和IR各自独立地与全因死亡率[风险比（95%置信区间）1.24（1.17 - 1.30）、1.63（1.55 - 1.72）和1.11（1.05 - 1.17）]和所有部位癌症[1.06（1.02 - 1.10）、1.14（1.10 - 1.19）和1.02（0.99 - 1.06）]风险的增加相关。联合分析显示，由于重度肥胖、炎症和IR之间的相互作用，全因死亡率和所有部位癌症的风险显著升高，最高风险比（95%置信区间）分别为1.88（1.67 - 2.11）和1.20（1.08 - 1.34）。进一步分析表明，重度肥胖、炎症、IR与生活方式之间的相互作用更强，在男性和女性中观察到类似的关联。此外，与不良生活方式相比，健康的生活方式降低了全因死亡率[健康生活方式与不良生活方式的最高风险比（95%置信区间）为2.35（1.75 - 3.15）对3.72（2.86 - 4.84）]和所有部位癌症[1.16（0.89 - 1.53）对1.63（1.26 -
