The aim of our prospective study of middle-aged NGT healthy subjects, many with a family history of diabetes (FHD), was to investigate the predictive power of the liver and adipose tissue specific biomarkers of insulin sensitivity, IGFBP-1, IGFBP-2 and adiponectin, as well as of IGF-I and IGF-II, to forecast development of prediabetes and T2D. This evidence concerns the gene INS and prediabetes syndrome.