| Title: | Metabolic syndrome and risk of sepsis and sepsis-related mortality: evidence from two large prospective cohort studies |
| Journal: | Military Medical Research |
| Published: | 27 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42088056/ |
| DOI: | https://doi.org/10.1016/j.mmr.2026.100031 |
Publication 20210
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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.</p>
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.</p>
Results: During a median follow-up of 13.7 years, 11,040 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 (HR=1.55, 95% CI 1.49-1.61) and 28-day mortality following sepsis (HR=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 P<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 (HR=1.91, 95% CI 1.81-2.00) and 28-day mortality following sepsis (HR=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 (HR=1.18, 95% CI 1.09-1.28 and HR=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 (HR=1.46, 95% CI 1.32-1.61) and 28-day mortality following sepsis (HR=1.88, 95% CI 1.50-2.35), followed by individuals with progressive MetS (HR=1.17, 95% CI 1.05-1.31 and HR=1.36, 95% CI 1.04-1.77, respectively), whereas those who recovered from MetS did not show a significantly increased risk (HR=1.09, 95% CI 0.96-1.25 and HR=1.19, 95% CI 0.87-1.61, respectively). Sensitivity analyses confirmed the robustness of the findings.</p>
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.</p>
13 Keywords
- Adult
- Aged
- Cohort Studies
- Female
- Humans
- Male
- Metabolic Syndrome
- Middle Aged
- Proportional Hazards Models
- Prospective Studies
- Risk Factors
- Sepsis
- United Kingdom
13 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 98583 | Associations of environmental and metabolic risk factors, and the interactions with genetic susceptibility loci with Risk of COVID-19, Chronic Disease and Mortality |
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