Since the previous studies have found that l-arginine is also able to improve endothelial [17–20], β-cell function [21, 22], and oxidative stress [23], the aim of this study was to investigate whether l-arginine may influence the incidence of new diabetic diagnosis, improving endothelial function, β-cell function, insulin sensitivity, and oxidative stress after 9 years from the initiation of an oral 18 month treatment with l-arginine in people at high risk for T2DM development. This evidence concerns the gene INS and type 2 diabetes mellitus.