Investigation of Isthmin-1 level in patients with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a prevalent endocrine-metabolic disorder among women of reproductive age, associated with hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Insulin resistance and lipid metabolism abnormalities are common in PCOS, increasing the risk of metabolic syndrome and type 2 diabetes mellitus (T2DM). Isthmin-1 (ISM1) is a novel adipokine that regulates glucose and lipid metabolism, but its role in PCOS remains unknown.  This study aimed to investigate whether serum ISM1 levels are altered in women with PCOS compared to healthy controls and whether ISM1 is associated with key metabolic (e.g., insulin resistance, homeostasis model assessment of insulin resistance [HOMA-IR]) and hormonal parameters (e.g., follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol [E2], testosterone, dehydroepiandrosterone sulfate [DHEA-S]). Emerging evidence highlights the role of novel adipokines in the metabolic dysregulation associated with PCOS. Among these, ISM1 has gained attention due to its insulin-mimetic effects and its role in glucose and lipid metabolism. Given the central role of insulin resistance and obesity in PCOS pathogenesis, investigating whether ISM1 is altered in women with PCOS could provide new insights into its potential role in disease mechanisms. Furthermore, exploring its association with insulin resistance markers may help determine whether ISM1 can serve as a supportive metabolic biomarker. Therefore, this study aimed to compare serum ISM1 levels between women with PCOS and healthy controls, and to examine the relationship between ISM1 levels and key metabolic and hormonal parameters.

This case-control study included 60 women aged 18-45 years: 30 women with PCOS diagnosed using the Rotterdam 2003 criteria and 30 age-matched healthy controls. Anthropometric measurements (body mass index [BMI], waist circumference), metabolic parameters (fasting/postprandial glucose, fasting insulin, HOMA-IR, hemoglobin A1c [HbA1c], lipid profile), and hormonal markers (FSH, LH, estradiol, testosterone, DHEA-S, prolactin, thyroid-stimulating hormone [TSH], free thyroxine [FT4]) were assessed. Serum ISM1 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses included independent t-tests, Mann-Whitney U tests, Spearman correlation, and ROC analysis.

Median ISM1 concentration was significantly higher in the PCOS group (1.60 ng/mL) compared to the control group (1.34 ng/mL, p = 0.03). ISM1 levels positively correlated with fasting insulin (r = 0.26, p = 0.04) and HOMA-IR (r = 0.29, p = 0.03). No significant correlation was found between ISM1 and reproductive hormones or lipid profile components. ROC analysis demonstrated that ISM1 had moderate diagnostic performance in identifying PCOS, with an area under the curve (AUC) of 0.658 (95% CI: 0.52-0.77, p = 0.026). At an optimal cut-off value of 1.85 ng/mL, the sensitivity was 43.3% and specificity was 90.0%.

Elevated serum ISM1 levels and their correlation with insulin resistance suggest that ISM1 may contribute to the metabolic pathophysiology of PCOS. Although its diagnostic performance is limited due to low sensitivity, ISM1 may serve as a supportive biomarker in identifying metabolic risk in women with PCOS. Further large-scale and mechanistic studies are needed to validate these findings and clarify the functional role of ISM1.