In this sense, it was proposed that hyperleptinaemia during the first trimester could significantly increase the risk of developing GDM by further accentuating the state of physiological IR via the release of tumour necrosis factor-alpha and interleukin 6 (IL-6) in the placenta.59 These inhibit the insulin intracellular signalling pathway and decrease its peripheral effects.60 Furthermore, the hyperleptinaemia would increase lipid mobilization, accentuating the lipotoxicity states of peripheral tissues.61 Here, INS is linked to gestational diabetes.