Concentrations of E2 exceeding 12 nM E2 are observed in a number of syndromes associated with INS resistance including third-trimester pregnancy, GDM, and OHSS, so that in these syndromes, more than half of the available INS will likely be bound to E2 at any given time, decreasing INS binding to its receptor (Figure 8). Here, INS is linked to gestational diabetes.