Association between systemic immune inflammation index and mortality risks in type 2 diabetes based on NHANES

Systemic immune-inflammation index (SII) integrates platelet, neutrophil, and lymphocyte counts (LYMPHs) and may reflect systemic inflammation and immune imbalance. Evidence on its prognostic value in type 2 diabetes mellitus (T2DM) remains limited. We investigated the association between SII and risks of all-cause and cardiovascular mortality in adults with T2DM. Data were derived from the National Health and Nutrition Examination Survey 1999 to 2018, including 6035 participants aged ≥ 20 years with T2DM. SII was calculated as platelet count × neutrophil count/ LYMPH and analyzed as both a continuous and a categorical variable (quartiles). Kaplan-Meier survival analysis, multivariable Cox proportional hazards models, and restricted cubic spline (RCS) analyses were performed to assess the association between SII levels and risks of all-cause and cardiovascular mortality. Subgroup analyses were performed to assess the robustness and consistency of the associations across different clinical strata. During a median follow-up of 82 months, 1808 (30.0%) of participants died from any cause and 780 (12.9%) from cardiovascular causes. All-cause cumulative mortality increased from 24.7% (Q1) to 37.6% (Q4); cardiovascular cumulative mortality from 10.9 to 16.4%. In fully adjusted models, each one-unit increase in SII was significantly associated with higher risks of all-cause mortality (HR = 1.15, 95% CI: 1.09-1.19, P < .001) and cardiovascular mortality (HR = 1.16, 95% CI: 1.09-1.22, P < .001). Compared with Q1, participants in Q4 had a 48% higher risk of all-cause death (HR = 1.48, 95% CI: 1.30-1.70, P < .001) and a 41% higher risk of cardiovascular death (HR = 1.41, 95% CI: 1.15-1.72, P = .001). RCS analysis suggested a nonlinear association, with mortality risks increasing steeply beyond an SII threshold of ~489. Exploratory subgroup findings showed no significant interactions. Elevated SII was significantly associated with higher risks of all-cause and cardiovascular mortality in patients with T2DM. These findings highlight the potential value of SII as a cost-effective and readily available biomarker for long-term risk stratification. However, given the observational nature of the study, causality cannot be inferred, and further prospective validation is warranted.