Metabolic syndrome and risk of sepsis and sepsis-related mortality: evidence from two large prospective cohort studies

Shao-Yu Liu; Shao-Kang Xu; Jing-Li Gao; Xiao-Ke Kong; Jian Shi; Ya Miao; Yi-Ting Tang; Bin Zhao; Fang Fang; Ai-Tian Wang; Shou-Ling Wu; Jia-Qi Huang; Ben Lu

doi:10.1016/j.mmr.2026.100031

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Metabolic syndrome and risk of sepsis and sepsis-related mortality: evidence from two large prospective cohort studies

RESEARCH | Updated：2026-05-11

- Metabolic syndrome and risk of sepsis and sepsis-related mortality: evidence from two large prospective cohort studies
- Military Medical Research (2026)
- Affiliations：
  
  Department of Critical Care Medicine and Hematology, the Second Xiangya Hospital, Central South University, Changsha 410011, China
  Department of Critical Care Medicine and Hematology, the Third Xiangya Hospital, Central South University, Changsha 410011, China
  Department of Intensive Medicine, Kailuan General Hospital, Tangshan 063000, Hebei, China
  National Clinical Research Center for Endocrine and Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, the Second Xiangya Hospital of Central South University, Changsha 410011, China
  CSU-Sinocare Research Center for Nutrition and Metabolic Health, Xiangya School of Public Health, Central South University; Furong Laboratory, Changsha 410011, China
  Hunan Provincial Clinical Research Center for Sepsis, the Third Xiangya Hospital, Central South University, Changsha 410011, China
  Department of Physiology, Xiangya School of Basic Medical Science, Central South University, Changsha 410011, China
  Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha 410011, China
  Institute of Environmental Medicine, Karolinska Institutet, Stockholm 171 77, Sweden
  Department of Cardiology, Kailuan General Hospital, Tangshan 063000, Hebei, China
- Author bio：
  
  Jia-Qi Huang, JIAQI.HUANG@CSU.EDU.CN
  *Ben Lu, XYBENLU@CSU.EDU.CN;
- Funds：
- DOI：10.1016/j.mmr.2026.100031
  CLC：
- Received：23 October 2025，
  
  Accepted：03 April 2026，
  
  Published：2026-04
- Accepted：
Scan QR Code
Liu SY, Xu SK, Gao JL, Kong XK, Shi J, Miao Y, et al. Metabolic syndrome and risk of sepsis and sepsis-related mortality: evidence from two large prospective cohort studies. Mil Med Res. 2026;13(1):100031.
DOI：

Liu SY, Xu SK, Gao JL, Kong XK, Shi J, Miao Y, et al. Metabolic syndrome and risk of sepsis and sepsis-related mortality: evidence from two large prospective cohort studies. Mil Med Res. 2026;13(1):100031. DOI： 10.1016/j.mmr.2026.100031.

摘要

Abstract

Background:

Metabolic syndrome (MetS) is characterized by chronic low-grade inflammation and immune dysregulation

which may increase susceptibility to sepsis. However

epidemiologic evidence remains limited. This study aimed to evaluate the association of MetS with the risk of sepsis and sepsis-related mortality.

Methods:

This study included 359

633 participants from the UK Biobank and 152

317 participants from the Kailuan Study. MetS was defined as the presence of ≥3 metabolic abnormalities. Multivariable Cox proportional hazards models were used to estimate hazard ratios (

HRs

) and 95% confidence intervals (CIs) for the associations of MetS with risk of sepsis and 28-day mortality following sepsis. Stratified analyses were conducted to assess potential effect modification. In the UK Biobank

we further evaluated the dose-response relationship between the number of MetS components and sepsis outcomes

explored potential mediation by inflammatory and immune biomarkers

and investigated the joint effect of MetS and lifestyle; in the Kailuan Study

we further investigated the impact of MetS evolution on sepsis risk. Sensitivity analyses were performed to evaluate the robustness of the results.

Results:

During a median follow-up of 13.7 years

040 sepsis cases were identified in the UK Biobank

whereas 5672 cases were documented in the Kailuan Study during a median follow-up of 16.4 years. After multivariable adjustment

MetS was associated with higher risks of sepsis (

=1.55

95% CI 1.49–1.61) and 28-day mortality following sepsis (

=1.51

95% CI 1.37–1.65) in the UK Biobank; corresponding

HRs

were 1.32 (95% CI 1.25–1.40) and 1.49 (95% CI 1.32–1.69) in the Kailuan Study

respectively (all

0.001). These associations were generally consistent across stratified analyses. Moreover

the risk of sepsis outcomes increased with the number of MetS components and was partly mediated by inflammation. Compared with individuals free of MetS

individuals with MetS and an unfavorable lifestyle had substantially higher risks of sepsis (

=1.9

95% CI 1.81–2.00) and 28-day mortality following sepsis (

=1.84

95% CI 1.64–2.07)

whereas those with MetS but a favorable lifestyle showed only a modestly increased risk of sepsis and no excess risk of 28-day mortality (

=1.18

95% CI 1.09–1.28 and

=1.05

95% CI 0.88–1.27

respectively). In analyses of MetS evolution

using individuals with persistently normal metabolic status as the reference

those with a persistent MetS demonstrated the highest risks of sepsis (

=1.46

95% CI 1.32–1.61) and 28-day mortality following sepsis (

=1.88

95% CI 1.50–2.35)

followed by individuals with progressive MetS (

=1.17

95% CI 1.05–1.31 and

=1.36

95% CI 1.04–1.77

respectively)

whereas those who recovered from MetS did not show a significantly increased risk (

=1.09

95% CI 0.96–1.25 and

=1.19

95% CI 0.87–1.61

respectively). Sensitivity analyses confirmed the robustness of the findings.

Conclusions:

This study demonstrated that MetS was associated with an increased risk of sepsis and sepsis-related mortality. These associations were partially mediated through inflammatory responses. The findings highlight the importance of maintaining metabolic health as well as promoting healthy lifestyles as strategies to reduce its burden.

关键词

Keywords

references

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