Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles
Abstract 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...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85519-9 |
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| author | Qianyun Jin Siwen Liu Yunmeng Zhang Yuting Ji Jie Wu Hongyuan Duan Xiaomin Liu Jingjing Li Yacong Zhang Zhangyan Lyu Fangfang Song Fengju Song Hua Li Yubei Huang |
| author_facet | Qianyun Jin Siwen Liu Yunmeng Zhang Yuting Ji Jie Wu Hongyuan Duan Xiaomin Liu Jingjing Li Yacong Zhang Zhangyan Lyu Fangfang Song Fengju Song Hua Li Yubei Huang |
| author_sort | Qianyun Jin |
| collection | DOAJ |
| description | Abstract 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/kg2), 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. |
| format | Article |
| id | doaj-art-9eda707a6ad146b19cd511eb7363b065 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-9eda707a6ad146b19cd511eb7363b0652025-01-12T12:17:54ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-025-85519-9Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestylesQianyun Jin0Siwen Liu1Yunmeng Zhang2Yuting Ji3Jie Wu4Hongyuan Duan5Xiaomin Liu6Jingjing Li7Yacong Zhang8Zhangyan Lyu9Fangfang Song10Fengju Song11Hua Li12Yubei Huang13Department 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 UniversityDepartment 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 HospitalDepartment 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 UniversityAbstract 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/kg2), 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.https://doi.org/10.1038/s41598-025-85519-9Severe obesityInflammationInsulin resistanceAll-cause mortalityAll-site cancersHealthy lifestyle |
| spellingShingle | Qianyun Jin Siwen Liu Yunmeng Zhang Yuting Ji Jie Wu Hongyuan Duan Xiaomin Liu Jingjing Li Yacong Zhang Zhangyan Lyu Fangfang Song Fengju Song Hua Li Yubei Huang Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles Scientific Reports Severe obesity Inflammation Insulin resistance All-cause mortality All-site cancers Healthy lifestyle |
| title | Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles |
| title_full | Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles |
| title_fullStr | Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles |
| title_full_unstemmed | Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles |
| title_short | Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles |
| title_sort | severe obesity high inflammation insulin resistance with risks of all cause mortality and all site cancers and potential modification by healthy lifestyles |
| topic | Severe obesity Inflammation Insulin resistance All-cause mortality All-site cancers Healthy lifestyle |
| url | https://doi.org/10.1038/s41598-025-85519-9 |
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