Relationship between systemic immune inflammation index and mortality among US adults with different diabetic status: Evidence from NHANES 1999-2018

Objective: To investigate the association between systemic immune inflammation index (SII) and all-cause or cardiovascular diseases (CVDs) mortality in US adults with different diabetic status based on the National Health and Nutrition Examination Survey (NHANES) database. Study design and setting: Adults with follow-up data in the NHANES 1999–2018 cycles were included in this study. The SII was calculated based on blood cells counts (including neutrophils, lymphocytes, and platelets) measured in the laboratory data. According to the quartiles of SII, population were divided into four groups (Q1-Q4). Mortality data was determined by linking NHANES survey participants to the National Death Index records, which collect mortality data and determine their vital status. Cox regression models were also performed to explore the hazard ratio (HR) and the corresponding 95 % confidence interval (95 % CI) of SII related with all-cause and CVDs mortality. In addition, restricted cubic spline was used to explore the nonlinear relationship between SII and mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of our results. Results: In this study, there were 45,454 participants were enrolled (50.43 % females), with a mean age of 47.35 ± 0.19 years. Among of which, 7971 were diabetes patients and 3281 were pre-diabetes. With the mean 9.89 ± 0.08 follow-up years, there were 6935 (15.26 %) deaths occurred. Of which, 1795 deaths were caused by CVDs. The age-adjusted death rates were higher in participants with high SII levels compared to those with low SII levels. Cox regression analysis, after adjusting for covariates, revealed that SII levels were associated with an increased risk of all-cause mortality (HR, 1.02; 95 % CI, 1.02–1.03, P < 0.0001) and CVDs mortality (HR, 1.05; 95 % CI, 1.02–1.08, P = 0.002) in the fully adjusted Model. Moreover, there was a slight increase in HR values with the progression of diabetes status. Restricted cubic spline analysis demonstrated a “U-shaped” relationship between SII and all-cause mortality in diabetic, pre-diabetic and non-diabetic populations (all the P for nonlinear < 0.001). In addition, the relationship between SII and CVDs mortality was also nonlinear in both the pre-diabetic and non-diabetic populations (both P < 0.001). However, there was a linear relationship between SII and cardiovascular mortality in individuals with diabetes (P = 0.528). Conclusion: The SII is closely associated with the risk of all-cause and cardiovascular mortality. These associations vary among individuals with different diabetic states. Therefore, monitoring systemic inflammation and SII values is crucial in mitigating the risk of mortality.