We have combined a comprehensive review of the literature on historical aspects of the glucose-centric approach to the diagnosis of PCOS with an up-to-date discussion of insulin physiology, the adaptive significance of IR, and the role of IR and hyperinsulinemia in PCOS, with a state-of-the-art AI generated insulin-centric model for the assessment and management of PCOS (IC-PAMM). This evidence concerns the gene INS and hyperinsulinism.