Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles

Sep 23, 2026

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Severe obesity often coexists with inflammation and insulin resistance (IR), raising concern for higher risks of death and cancer, though the relationship remains debated and the extent to which healthy lifestyles can lessen harm is unclear. Using 163,008 UK Biobank participants, severe obesity (BMI ≥ 35), inflammation (CRP > 10 mg/L and systemic markers > 9th decile), and IR surrogates were tested for independent and joint links with all-cause mortality and all-site cancers. Over 11.0 years, deaths and cancer cases were identified, and the combined triad showed interaction-driven risk elevation. Favorable lifestyles attenuated these risks, supporting lifestyle adherence for risk mitigation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Background

Rationale and study aims

Methods and analysis

Cohort and follow-up

Independent and joint associations

Lifestyle modification analyses

Results

Mortality and cancer risks

Interaction effects

Conclusions

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Severe obesity, high inflammation, insulin resistance with risks of all-cause mortality and all-site cancers, and potential modification by healthy lifestyles Qianyun Jin1,3, Siwen Liu1,3, Yunmeng Zhang1, Yuting Ji1, Jie Wu1, Hongyuan Duan1, Xiaomin Liu1, Jingjing Li1, Yacong Zhang1, Zhangyan Lyu1, Fangfang Song1, Fengju Song1, Hua Li2􀀍 & Yubei Huang1􀀍 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’sunclear 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 followup 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 allcause mortality and all-site cancers. Nonetheless, adherence to healthy lifestyles is recommended to mitigate these increased risks. Keywords Severe obesity, Inflammation, Insulin resistance, All-cause mortality, All-site cancers, Healthy lifestyle Cancer is one of the leading causes of death worldwide. According to the global cancer statistics reported in 20201, cancer is the primary or secondary leading cause of death in 112 countries. It not only represents a significant burden of disease but also plays a crucial role in limiting human life expectancy. A substantial reduction in cancer mortality through effective and high-quality preventive strategies is essential to advancing the Sustainable Development Goals related to non-communicable diseases2. 1Department 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. 2Department 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. 3Qianyun Jin and Siwen Liu contributed equally to this work. 􀀍 email: [lihualixing@126.com](lihualixing@126.com); [yubei_huang@163.com](yubei_huang@163.com) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) Excess body weight, indicated by an increased body-mass index (BMI), is a major public health concern, with obesity prevalence rising globally in recent dec

FAQs

What study question addresses the relationship between severe obesity and health outcomes?

The study evaluates whether severe obesity, inflammation, and insulin resistance independently and jointly relate to all-cause mortality and all-site cancers, and whether healthy lifestyles can modify these associations.

How were severe obesity, inflammation, and insulin resistance defined in the analysis?

Severe obesity was defined by BMI ≥ 35 kg/m². Inflammation used CRP > 10 mg/L plus systemic inflammation markers above the 9th decile, while insulin resistance was assessed using IR surrogate measures.

What did the joint analyses show about combined severe obesity, inflammation, and insulin resistance?

Joint analyses demonstrated significantly elevated risks for both all-cause mortality and all-site cancers, with interaction effects and the highest hazard ratios reported for the combined triad.

How did healthy lifestyles influence the risks reported in the study?

Compared with unfavorable lifestyles, favorable lifestyles attenuated the increased risks of all-cause mortality and reduced risks of all-site cancers, indicating lifestyle adherence may mitigate the heightened outcomes.

Sep 23, 2026

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