Diabetic Complications of the Central Nervous System

DIABETES mellitus is a metabolic disorder associated with structural and functional alterations of various organ systems. The tissue injury is attributed primarily to chronic hyperglycemia. Although the peripheral neuropathy along with the small and large blood vessel disease can explain most of the diabetes-related organ failure, we have been increasingly more aware over the last two decades that the deleterious effects of chronic hyperglycemia extend beyond neuropathy and angiopathy. Examples of such diabetic complications include cataractous opacification of the lens (1–3), altered immune system (4–7), cardiomyopathy in the absence of appreciable intramural bloodvessel disease (8–10), alterations in specific transport functions of the intestine (11–16), and central nervous system (CNS) dysfunction. Thus glucotoxicity is not tissue specific, albeit the severity of organ system dysfunction in diabetes is highly variable. In contrast to the high prevalence rate of renal failure in diabetic patients, except for retinal disease, the chronic diabetic complications of the CNS are subtle and often unrecognized. Whereas the CNS effects of acute alterations in blood glucose level are well known, the effect of chronic hyperglycemia on brain metabolism and cognitive function is not widely appreciated.