Diabetes and Obesity Biomarkers in Association with Hyperandrogenism Reveal Key Networks in the Pathogenesis of Polycystic Ovary Syndrome: Study on a Cohort from the Southern Part of Kerala State

Polycystic Ovary Syndrome (PCOS) is a multisystemic disorder that is strongly associated with comorbid factors such as insulin resistance and obesity. PCOS women with high androgen levels are known to potently regulate insulin metabolism and increase the risk of type 2 Diabetes. Several diabetic biomarkers have been implicated, but how these biomarkers correlate with each other and the mechanistic pathways involved are poorly understood. Therefore, this study aims to comprehend the correlation and various pathways through which these key regulators interact with each other to regulate the PCOS-diabetes-obesity network. We conducted a retrospective cohort study, including 76 controls and 67 PCOS subjects. Plasma levels of 10 different diabetic and obesity biomarkers were measured by multiplex beads assay. Further, statistical correlation analysis and GOnet network prediction were done to understand the specific pathways altered in PCOS conditions. The levels of five biomarkers (ghrelin, C-peptide, insulin, and adipokines (leptin, and visfatin) were significantly changed in PCOS subjects. Regression and correlation analysis showed a significant correlation between ghrelin, C-peptide, insulin, leptin, visfatin, and high testosterone. Finally, GOnet network analysis revealed various processes and pathways including altered glucose metabolism, inflammatory response, cytokines production, regulation of stress, defective nitric oxide regulation, and impaired circadian rhythm. Our findings indicate intertwined metabolic-physiological-inflammatory complications in the pathogenesis of PCOS, highlighting the comorbidities between PCOS pathogenesis, diabetes, obesity, and inflammation.