Diabetes And Dementia

Several well-designed epidemiological studies support the notion that T2DM likely increases the risk for dementia. Investigators in Honolulu Asia Aging Study reported that T2DM increased the incidence of Alzheimer's disease and vascular dementia among Japanese-Americans (20). Consistent with these findings, investigators for the Mayo and Rotterdam groups reported that the presence of T2DM increased the risk for Alzheimer's disease, independent of vascular dementia (21, 22) and Luchsinger et al. reported that hyperinsulinemia, a condition associated with early T2DM and impaired glucose tolerance, increased the risk for both memory impairment and Alzheimer's disease (15). Autopsy studies have not confirmed this relationship between Alzheimer's disease and T2DM (23). Therefore, diabetes may increase the risk for serious memory loss, presenting very much like Alzheimer's disease with a different pathophysi-ology than typical Alzheimer's disease. Convergent evidence supports the notion that insulin plays a role in both the beneficial effects of acute hyper-glycemia and the detrimental effects of chronic hyperglycemia on cognition. As we previously noted, an acute rise in plasma glucose is rapidly followed by a rise in plasma insulin. Therefore, the beneficial effects attributed to increased plasma glucose levels may, in part, reflect effects of increased plasma insulin levels. (We will present evidence supporting this possibility in the following section.) However, detrimental effects may follow chronic glucose and insulin elevations. In T2DM, hyperglycemia is produced by two deficits: insulin resistance and insufficient compensatory insulin secretion by pancreatic ^ cells. Insulin resistance, or reduced insulin sensitivity, is characterized by a reduction in the ability of insulin to promote glucose disposal. Consequently, more insulin is needed to promote glucose utilization. This heightened compensatory response results in elevated plasma levels of glucose and insulin in patients with impaired glucose tolerance and early T2DM.

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