When these changes abnormally activate the pathways of glucose metabolism, such as protein kinase C pathway and polyol pathway, it is possible to cause the dysregulation of cytokine control by the persistent hyperglycemia.[40] This could progress into DN through the activation of NF‐κB that can exacerbate the inflammatory mediators, such as TNF‐α, IL‐1β, and IL‐6 thorough persistent activation of the oxidative stress pathway regardless of the blood glucose control.[56] The exacerbations of these mediators may also be involved in microvascular damage. This evidence concerns the gene NFKB1 and Hyperglycemia.