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

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder frequently associated with insulin resistance (IR) and increased cardiovascular risk. Soluble CD40 ligand (sCD40L) and soluble E-selectin (sE-selectin) are circulating biomarkers reflecting immune activation and endothelial dysfunction, respectively. However, their differential associations with IR in PCOS, particularly in the context of central obesity, remain incompletely understood. This cross-sectional study included 80 women with PCOS stratified according to waist-to-height ratio (WHtR > 0.50 vs. ≤0.50). Clinical, metabolic, hormonal, inflammatory, and endothelial parameters were evaluated. Correlation and multivariable regression analyses were performed to identify independent determinants of circulating sCD40L and sE-selectin. Women with central obesity exhibited significantly higher fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, systolic blood pressure (SBP), and sE-selectin concentrations, together with lower HDL cholesterol. No significant differences were observed in tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), or sCD40L. In adjusted regression models, fasting glucose independently predicted sCD40L (β = -0.27, 95% confidence interval (CI): -0.50 to -0.04, p = 0.020), whereas fasting insulin emerged as the strongest determinant of sE-selectin (β = 0.41, 95% CI: 0.17 to 0.65, p < 0.001). These findings suggest distinct associations of immune and endothelial biomarkers with IR in PCOS. Assessment of sCD40L and sE-selectin may provide complementary information for early cardiometabolic risk stratification in affected women.