Cognitive function and peripheral glucose regulation both decrease with age. There is a consistent and growing literature reporting memory and other cognitive problems among individuals with diabetes mellitus as well as those with pre-diabetes. There are two papers in the literature documenting, relative to matched controls, hippocampal volume reductions among both diabetics and insulin resistant individuals. The mechanism(s) for the cognitive and brain problems associated with impairments in peripheral glucose regulation remain unknown. In this paper, I present a selective review of the literature that builds a case for a theoretical model that could be used to investigate how abnormalities in peripheral glucose regulation may give rise to brain impairments in general, and affect hippocampal integrity in particular.