In diabetes, high glucose levels in the plasma and other metabolic abnormalities such as hyperinsulinemia can damage the BBB and then cause hyperglycemia in CSF (Nigrovic et al., 2012; Bogush et al., 2017; Arnold et al., 2018), which can subsequently contribute to impaired insulin signaling, mitochondria dysfunction, oxidative stress, and inflammation in the brain (Szendroedi et al., 2011). This evidence concerns the gene INS and diabetes mellitus.