Dissociation of inflammatory and endothelial axes from insulin resistance in classic polycystic ovary syndrome: A BMI-matched case-control study from Iraq

Abstract

Objective: To test whether the inflammatory marker lipocalin‑2 and the endothelial marker vasorin carry information independent of insulin resistance severity in classic polycystic ovary syndrome (PCOS) phenotypes A/B.

Methods: This BMI‑matched case–control study recruited 60 women with classic PCOS (Rotterdam phenotypes A/B) and 60 non‑PCOS controls (18–40 years) from Iraqi hospitals. Fasting glucose, triglycerides, total testosterone, sex hormone‑binding globulin, lipocalin‑2 (ELISA) and vasorin (ELISA) were measured. Insulin resistance was estimated using the triglyceride–glucose (TyG) index. Analyses included Spearman correlations, multiple linear and logistic regression, and within‑PCOS TyG tertile stratification.

Results: PCOS cases had higher TyG index, lipocalin‑2 (731.1±196.8 vs 489.2±144.1 ng/L, p<0.0001) and lower vasorin (median 92.81 vs 115.20 pg/mL, p=0.003) despite similar BMI (p=0.064). Lipocalin‑2 correlated strongly with TyG (rₛ=0.787, p<0.0001) and remained an independent predictor of PCOS status (OR 1.014, 95%CI 1.009–1.020). Vasorin correlated modestly with TyG (rₛ=0.391, p=0.002) and did not independently predict TyG (p=0.176), but retained an inverse association with PCOS after adjustment for lipocalin‑2 (OR 0.944, 95%CI 0.915–0.968). Within PCOS, vasorin showed a non‑monotonic U‑shaped trajectory across TyG tertiles (p=0.004), whereas lipocalin‑2 increased monotonically.

Conclusions: Lipocalin‑2 is tightly coupled to insulin resistance yet independently associated with PCOS. Vasorin is dissociated from insulin resistance severity, supporting the view that endothelial alterations in PCOS are partly independent of metabolic dysfunction. Routine laboratory TyG and lipocalin‑2 offer pragmatic triage, but all cut‑offs require external validation.