Age-specific association between remnant cholesterol and insulin resistance in women with polyendocrine metabolic ovarian syndrome

Abstract

Insulin resistance (IR) is a major metabolic feature in women with polyendocrine metabolic ovarian syndrome (PMOS). Remnant cholesterol (RC), which reflects the cholesterol burden of triglyceride-rich remnant lipoproteins (TRLs), may capture lipid disturbances related to insulin-resistant dyslipidemia. Whether RC is linked to IR in women with PMOS remains unclear. This study enrolled 617 women with PMOS. Participants were grouped according to natural-log-transformed remnant cholesterol (lnRC) quartiles. Adjusted odds ratios (ORs) for IR were estimated using multivariable logistic regression models, and restricted cubic splines (RCS) were fitted to characterize the potential dose-response patterns. Multiplicative and additive interaction analyses were performed to evaluate the interaction between age and lnRC. Discrimination of IR by lnRC was assessed using receiver operating characteristic (ROC) curve, and age-specific estimates were compared using DeLong’s test. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to assess whether lnRC added information beyond the base model. Higher lnRC levels were significantly associated with increased odds of IR (Q4 vs. Q1: odds ratio [OR] = 3.11, 95% confidence interval [CI]: 1.57–6.14, P  = 0.001). This relationship was stronger in women aged < 30 years than in those aged ≥ 30 years (OR: 2.01 vs. 1.13, P for interaction = 0.046). A multiplicative interaction between age and lnRC was also observed for IR (OR = 0.438, 95% CI: 0.197-0.977, P  = 0.044). Exploratory age-stratified ROC analysis showed that the area under the curve (AUC) of lnRC for IR discrimination was higher among women aged <30 years than among those aged ≥30 years (0.654 vs. 0.523, DeLong P = 0.024). Adding lnRC to the base model improved risk reclassification and discrimination (NRI = 0.381, 95% CI: 0.165–0.597, P  = 0.001; IDI = 0.025, 95% CI: 0.007–0.0439, P  = 0.005). This study indicates that the lnRC–IR association was stronger in women aged <30 years, and a multiplicative interaction between lnRC and age group was observed. These findings suggest that RC may provide complementary information for metabolic assessment in younger women with PMOS and support its further evaluation as a readily calculable lipid marker.