Dickkopf1 (DKK1) as a Potential Biomarker in Polycystic Ovary Syndrome and Insulin Resistance: A Cross-Sectional Study

Abstract

Abstract Background: Dickkopf1 (DKK1) isa protein with established links to metabolic diseases. However, its association with polycystic ovary syndrome (PCOS) and insulin resistance (IR) remains ambiguous. Methods: We conducted a cross-sectional study involving 300 participants, including 100 healthy women, 100 women with PCOS, and 100 individuals with IR. We used the STRING database to identify proteins that interact with DKK1 and performed KEGG and GO analyses to determine the biological processes and signaling pathways that are enriched in DKK1-related proteins. Serum DKK1 levels and Adipoq were measured by ELISA kits. The expression of DKK1 in liver tissue wasdetected by western blotting. Results: Relative to the control group, both the IR and PCOS cohorts exhibited markedly elevated serum DKK1 levels and noticeably reduced Adipoq levels. Correlation analyses revealeda positive relationship between serum DKK1 levels and 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), and homeostasis model assessment of insulin resistance (HOMA-IR) and a negative relationship between Adipoq levels and M-value. Multiple regression analysis indicated that BMI, FAT%, TG, and Adipoq were independent factors affecting DKK1. An analysis of multiple stepwise regressions revealed that DKK1 was a risk factor for IR and PCOS. In the euglycemic-hyperinsulinemic clamp (EHC) test, serum DKK1 levels exhibited a significant increase in the PCOS patients and a pronounced decrease in the IR patients at 30 minutes and returned to baseline at 60 minutes. Conclusions: Our research revealedthat an increase in DKK1 levels in the blood was significantly associated with PCOS and IR, thereby highlighting the potential involvement of DKK1 in the pathogenesis of PCOS and IR. This insight paves the way for further investigations into the role of DKK1 in PCOS and IR.