APOE and Insulin resistance: Sirt 1’s links to insulin resistance (Figure 3) are associated with high plasma sodium levels [87,88,89] and low VIP levels, which contribute to coronary events [90] and vascular effects in the central nervous system that determine peripheral amyloid beta metabolism and transport of amyloid beta across the blood–brain barrier [91,92] and are important to the role of VIP in the regulation of apo E-mediated amyloid beta clearance pathways in the brain and the liver [21,23,93].