Dickkopf1 as a Potential Biomarker in Polycystic Ovary Syndrome and Insulin Resistance: A Cross-Sectional Study

Dickkopf1 (DKK1) is a protein with established links to metabolic diseases. However, its association with polycystic ovary syndrome (PCOS) and insulin resistance (IR) remains ambiguous.

We conducted a cross-sectional study involving 300 participants, including 100 healthy women, 100 women with PCOS, and 100 individuals with IR. Protein interactions with DKK1 were identified using the STRING database, followed by KEGG and GO analyses to explore enriched biological processes. Serum DKK1 and Adipoq levels were measured using ELISA kits. The hepatic DKK1 was detected by western blotting.

Both IR and PCOS groups showed significantly higher serum DKK1 levels and lower Adipoq levels compared to controls. Serum DKK1 levels positively correlated with body mass index (BMI), waist-hip ratio (WHR), body fat percentage (FAT%), systolic blood pressure (SBP), triglycerides (TG), fasting plasma glucose (FPG), fasting insulin (FIns), glycosylated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR). Adipoq levels negatively correlated with glucose disposal rate (M-value). Multiple regression analysis showed that BMI and Adipoq were independent factors affecting DKK1. Multiple stepwise regressions indicated that DKK1 is a risk factor for IR and PCOS. In the euglycemic-hyperinsulinemic clamp (EHC) test, serum DKK1 levels increased in the PCOS patients and decreased in the IR patients at 30 min and returned to baseline at 60 min.

Elevated DKK1 levels are strongly associated with PCOS and IR, suggesting a potential role in their development. This insight paves the way for further investigations into the role of DKK1 in PCOS and IR.