Key components of β cell failure in T2DM involves: (1) loss of cell identity, specifically a reduction of transcription factors associated with mature cell function (NEUROD1, FOXO1, MAFA, PDX-1, NKX2.2, NKX6.1), as well as (2) de-differentiation, defined by regression to a progenitor or stem cell-like state [555,556,557]. This evidence concerns the gene NKX2-2 and type 2 diabetes mellitus.