INS and obesity due to melanocortin 4 receptor deficiency: Chronic peripheral and inflammation induced by DM and obesity can cause BBB breakdown and permeability to infiltrating macrophages, leading to exacerbation of the immune response in the brain, disruption of glial and neuronal cell integrity, impaired hormonal function, increased insulin insensitivity and impaired cognition (van Dyken & Lacoste, 2018).