Divergent Immune and Endothelial Responses to Insulin Resistance in Women with Polycystic Ovary Syndrome

Abstract Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine–metabolic disorder commonly associated with insulin resistance and early cardiovascular dysfunction. Soluble CD40 ligand (sCD40L) and soluble E-selectin (sE-selectin) are circulating markers reflecting immune activation and endothelial stress, respectively. This cross-sectional study investigated 80 women with PCOS, stratified by central obesity (waist-to-height ratio, WHtR > 0.50 vs ≤ 0.50). While age and systemic inflammatory markers (TNF-α, IL-6) did not differ significantly between groups, centrally obese women exhibited higher fasting insulin, HOMA-IR, triglycerides, non-HDL cholesterol, systolic blood pressure, and sE-selectin, together with reduced HDL cholesterol. In multivariable models adjusted for age, body mass index (BMI) and waist circumference, fasting glucose independently predicted sCD40L (β = 0.27, p = 0.02), whereas fasting insulin was the strongest determinant of sE-selectin (β = 0.41, p < 0.001). These findings reveal divergent immune and endothelial responses to insulin resistance in PCOS, underscoring the potential utility of sCD40L and sE-selectin as complementary biomarkers for early cardiometabolic risk stratification and personalised management in affected women.