INS and type 2 diabetes mellitus: Initial studies evaluating DNA methylation in candidate genes for T2D (e.g., IRS, GLP1-R, encoding the receptor for GLP-1, PPARGC1A, encoding the peroxisome proliferator-activated receptor γ coactivator-1 alpha, a transcriptional co-activator involved in cellular energy metabolism [205]) found that the DNA methylation level in pancreatic islets of T2D subjects was lower than that of non-diabetic control, with a consequent reduced expression of these pivotal genes, which can explain the impaired insulin secretion, high glucose, and Hb1Ac levels [189].