Consequently, while FGF21 levels may have protective effects against T2DM in its early phase, chronic hyperglycemia-induced FGF21 resistance is proposed to be the mechanism explained by the result of our study, where increased serum FGF21 levels initially aim to repair microvascular damage in retinopathy, serving as a counteractive mechanism against metabolic stress and vascular endothelial damage in DR (Frudd et al., 2022; Jin, Xia & Han, 2021; Rusu et al., 2017). This evidence concerns the gene FGF21 and type 2 diabetes mellitus.