GCK and type 2 diabetes mellitus: While TCF7L2 isoforms are not significantly altered in T2D (Prokunina-Olsson et al., 2009), both HNF-1α and GCK diabetes associated alleles result in alternative splicing variation (Cappelli et al., 2009; Lorini and D’Annunzio, 2009), and isoforms of HNF-1α are associated with differential efficiency in insulin gene regulation (Harries et al., 2006; Cappelli et al., 2009).