Given that circulating free (35) as well as total (36) IGF-I appears to influence insulin sensitivity, we hypothesized that the strong associations observed with GDM, high blood pressures, and insulin sensitivity are underpinned by PAPP-A regulating IGF bioavailability in pregnancy, which in turn regulates insulin sensitivity and ultimately contributes to protection against, or the development of, certain adverse conditions of pregnancy. This evidence concerns the gene IGF1 and gestational diabetes.