Cognitive impairment in diabetes and poor glucose utilization in the intracellular neural milieu.

The main characteristic of diabetes is hyperglycemia. Depending on whether diabetes is type-1 or type-2, it is characterized by deficiencies in insulin secretion, insulin receptor sensitivity, hexokinase activity, and glucose transport. Current drug treatments are able to lower circulating glucose but do not address the problem of glucose utilization in the intracellular milieu, the consequence of which is tissue damage. In the long-term, such changes can produce structural damage in many cortical and subcortical brain areas that are related to cognitive function. Many epidemiological reports consider anxiety and depression as clinical entities that accompany diabetes. However, anxiety and depression in diabetes appear to occur in parallel and do not follow a causal relationship. From a behavioral perspective, anxiety may be considered adaptive, whereas depression can be considered reactive in response to changes in lifestyle and ailments that are caused by the disease. Therefore, the main alteration in diabetes seems to be cognitive function. We hypothesized that in type-2 diabetes, hypoglycemic medications do not restore the function of glucose in the intracellular compartment, which may have deleterious effects on neural tissue with behavioral consequences. In such a case, it is important to develop pharmacological interventions that directly restore plasma insulin levels, insulin receptor function, and hexokinase activity, thereby avoiding damage to neural tissue that is associated with cognitive deficits in diabetic patients, particularly patients with type-2 diabetes. The better management of such alterations in diabetes should be directed toward improving glucose utilization by neural tissue.