INS and polycystic ovary syndrome: It has been demonstrated that profound IR in PCOS due to peripheral target tissue resistance, decreased hepatic clearance, beta-cell dysfunction and increased pancreatic sensitivity [74, 75] is exacerbated through innate IR during pregnancy mainly by the secretion of some insulin-desensitizing placental adipokines and hormones including tumor necrosis factor (TNF)-α, growth hormone, cortisol and human placental lactogen [63, 76].