Abstract
BACKGROUND: Obesity has been shown to reduce short-term mortality in sepsis patients, but the main subgroups and its role in immune-related inflammatory status require further research. The aim of this study was to identify the primary beneficiaries of the sepsis-obesity paradox and to investigate the involvement of immune-inflammatory status. METHODS: In this study, we analyzed data from 6602 sepsis patients from the MIMIC-IV database. Body mass index (BMI) was divided into quartiles, and mortality rates were assessed for each interval. Logistic trend tests and subgroup and restricted cubic spline (RCS) analyses were performed. Blood biochemical indicators were compared across different BMI ranges and between survivors and non-survivors. The receiver operating characteristic (ROC) curve for 28-day mortality was also evaluated. RESULTS: The 28-day mortality of sepsis patients followed a U-shaped pattern with increasing BMI. Trend analysis confirmed that BMI was a significant risk factor for 28-day mortality (p < 0.05). Subgroup analysis revealed an interactive effect of BMI on 28-day mortality in elderly (≥ 65 years old), male, and non-septic shock individuals (p < 0.05). A higher BMI was associated with an increased lymphocyte proportion and decreased neutrophil proportion, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) (p < 0.05). Compared with survivors, non-survivors had lower lymphocyte proportions and higher neutrophil proportions, NLRs, and SIIs. ROC analysis revealed that the lymphocyte and neutrophil proportions, NLR, and SII had predictive value for 28-day mortality. Subgroup and RCS analyses revealed that increased BMI was associated with reduced 28-day mortality in sepsis patients, mainly in elderly, male, and septic shock individuals, with protective BMIs ranging from 27.8 ~ 41.7 kg/cm(2), 28.4 ~ 37.7 kg/cm(2), and > 28.6 kg/cm(2), respectively. CONCLUSIONS: The sepsis-obesity paradox significantly affects elderly (≥ 65 years old), male, and non-septic shock individuals, displaying a U-shaped pattern for 28-day mortality. BMI may mediate this phenomenon by influencing the body's immune-inflammatory status.