Elevated Systemic Immune-Inflammation Index is Associated with Gestational Diabetes Mellitus: A Multicenter Retrospective Studies

Background: The systemic immune-inflammation index (SII), an integrative biomarker reflecting inflammatory and immune status, has been implicated in metabolic disorders. However, its association with gestational diabetes mellitus (GDM) remains unclear. This study aimed to investigate whether elevated SII is associated with an increased risk of GDM. Objective: We aimed to clarify whether systemic SII is related to the occurrence of GDM and the relationship between changes in SII and adverse pregnancy outcomes associated with GDM. Methods: This study analyzed 47,480 singleton pregnancies between 2018 and 2024, including 6599 GDM cases and 40,881 controls. SII was calculated before 24 weeks of gestation, and participants were categorized by SII quartiles. Multivariable logistic regression was used to assess associations between SII and GDM (primary outcome), insulin-requiring GDM (A2), preeclampsia, and large-for-gestational-age infants. In addition, interaction tests and smooth curve fitting methods were adopted to explore the relationship between SII and gestational diabetes mellitus (GDM) and related adverse pregnancy outcomes. Results: After adjustment, higher SII quartiles showed a dose-dependent increase in GDM risk: Q2 (aOR = 1.19, 95% CI: 1.08-1.30), Q3 (aOR = 1.26, 1.15-1.38), Q4 (aOR = 1.56, 1.43-1.71; P < 0.0001). Stronger associations were observed for GDM A2 and GDM with preeclampsia. The association with LGA was weaker and only significant in Q3. Subgroup analyses revealed consistent associations across age and BMI, though the effect was marginally stronger in multiparous women (interaction P=0.0213<0.05). No significant interactions were found for BMI or age. Conclusion: Elevated SII in early pregnancy is independently associated with an increased risk of GDM, supporting its potential utility as an early predictive marker for GDM screening.