Although the interplay between inflammation and diabetes is increasingly recognized, it is unclear whether the systemic immunity-inflammation index (SII), as a biomarker of systemic inflammatory response, is associated with type 2 diabetes (T2D) and insulin resistance (IR). This cross-sectional study was performed in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, and finally enrolled 17,017 participants. To explore the relationship between SII and T2D and IR, a series of statistical analyses were conducted including weighted multivariate linear regression, logistic regression, and subgroup analysis. The fully adjusted multivariate linear regression revealed a positive correlation between SII and fasting plasma glucose (β = 0.13, 95% CI: 0.01, 0.24), fasting serum insulin (β = 12.90, 95% CI: 6.77, 19.04), and homeostasis model assessment of insulin resistance (β = 0.68, 95% CI: 0.25, 1.10). A per-SD increase in SII was found to be associated with a 4% increase in the odds of T2D, and a 5% increase in the odds of IR. The trend was significant across all SII quartile groups. Subgroup analysis revealed a stronger positive association existed between SII and T2D and IR in female, younger, and obese populations. SII was positively associated with the risk of T2D and IR, indicating that reducing SII levels may help prevent these conditions in the general population.

Association of systemic immunity-inflammation index with type 2 diabetes and insulin resistance in NHANES 2005–2018