SHBG and type 2 diabetes mellitus: There is evidence showing a more direct role for SHBG through an intracellular signaling cascade mediated by a membrane-bound SHBG receptor.15,16 Delineation of the biological effect of SHBG signaling has lagged behind our understanding of the biochemical analysis of its cAMP signaling pathway; however, epidemiological studies on subjects of European ancestry have reported an inverse association between low circulating SHBG and type 2 diabetes.17,18 This means that those with higher serum levels of SHBG are protected from developing type 2 diabetes.