Background The triglyceride-glucose (TyG) index, a validated surrogate marker of insulin resistance, has been widely investigated for its associations with cardiovascular outcomes in both diabetic and non-diabetic populations. However, its potential role in sepsis development remains largely unexplored. Moreover, whether the relationship between the TyG index and sepsis risk differs according to diabetes status has not been systematically examined. Methods and results In this prospective cohort study, we analyzed 428,207 participants from the UK Biobank who had baseline TyG index measurements and no prior history of cardiovascular disease. Associations between the TyG index and sepsis incidence and sepsis-related mortality were assessed using Cox proportional hazards models, with stratification by diabetes status to evaluate potential effect modification. Over a median follow-up of 13.04 years, 12,410 sepsis events and 6,291 sepsis-related deaths were documented. Among individuals with diabetes, the relationship between the TyG index and both sepsis incidence and mortality was linear, whereas a U-shaped association was observed in non-diabetic participants. After adjustment for potential confounders, each 1-unit increase in the TyG index was associated with an 18% higher risk of sepsis (hazard ratio HR: 1.18; 95% confidence interval CI: 1.10–1.27) and a 16% higher risk of sepsis-related mortality (HR: 1.16; 95% CI: 1.05–1.27) in the diabetic subgroup. In contrast, no significant associations were observed among non-diabetic participants for either sepsis incidence (HR: 1.02; 95% CI: 0.98–1.06) or sepsis-related mortality (HR: 0.99; 95% CI: 0.94–1.05). Importantly, inclusion of the TyG index improved the predictive performance of risk models for both outcomes in individuals with diabetes. Conclusion These findings demonstrate a diabetes-status-dependent association between the TyG index and sepsis outcomes. Elevated TyG levels were linearly and independently associated with increased risks of sepsis and sepsis-related mortality in diabetic individuals, whereas no significant associations were observed in non-diabetic participants. This suggests that the TyG index may serve as a clinically useful biomarker for sepsis risk stratification in patients with diabetes, warranting further validation in external cohorts.
You et al. (Thu,) studied this question.