SYNERGISTIC METABOLIC DYSFUNCTION: INVESTIGATING THE INTERPLAY BETWEEN PCOD, INSULIN RESISTANCE, AND NON-ALCOHOLIC FATTY LIVER DISEASE(NAFLD)

Jerina CA., Ashini David, *Dr. Alwin Simon

ABSTRACT

Polycystic ovary syndrome (PCOS), insulin resistance (IR), and non-alcoholic fatty liver disease (NAFLD) are highly prevalent metabolic disorders that frequently coexist through interconnected pathophysiological mechanisms. Their bidirectional relationship is driven by shared processes, including hyperinsulinemia, chronic low-grade inflammation, oxidative stress, adipokine dysregulation, mitochondrial dysfunction, and genetic and epigenetic alterations, resulting in a self-perpetuating cycle that accelerates disease progression. This review summarizes current evidence on the molecular and clinical interplay among PCOS, IR, and NAFLD, highlighting overlapping clinical manifestations, diagnostic challenges, and emerging biomarkers. It further examines the influence of environmental and lifestyle factors, including dietary habits, sedentary behaviour, endocrine-disrupting chemicals, and gut microbiota dysbiosis, on metabolic dysfunction. Current management strategies involving lifestyle modification, insulin-sensitizing agents, glucagon-like peptide-1 receptor agonists, and multidisciplinary care are discussed alongside emerging therapeutic approaches targeting epigenetic regulation and the gut microbiome. Despite significant advances, the absence of unified diagnostic criteria and limited longitudinal evidence continue to hinder integrated management. A comprehensive understanding of the synergistic relationship among PCOS, IR, and NAFLD may facilitate earlier diagnosis, improve risk stratification, and support the development of personalized therapeutic strategies. Future research should prioritize integrated clinical models, molecular biomarkers, and artificial intelligence-based precision medicine to improve long-term metabolic and reproductive outcomes.

Keywords: Adipokines, Precision Medicine, Chronic inflammation, Polycystic Ovary Syndrome, Non-Alcoholic Fatty Liver Disease(NAFLD).