Although one study demonstrated that at-risk subjects who progressed to T1D had higher levels of unmethylated insulin-coding cell-free DNA (INScfDNA) compared with healthy controls [20], there is no knowledge of whether an increased amount of unmethylated circulating INScfDNA could serve as a predictor of T2D, as there are no longitudinal studies of cohorts with an increased risk of T2D. This evidence concerns the gene INS and type 2 diabetes mellitus.