Diabetes and brain damage: more (or less) than meets the eye?

Excerpt

Brain damage is now a well-established complication of diabetes, but its pathophysiological basis remains controversial. Until very recently, most research on this topic was devoted to demonstrating that hypoglycaemic events are the primary cause of neurocognitive dysfunction. This was a plausible hypothesis because the central nervous system (CNS) has very limited stores of glucose and other substrates, but neurons have a very high rate of glucose utilisation; any reduction in glucose availability would probably induce neuroglycopenia, ultimately leading to significant neuronal damage. Support for this view came from research demonstrating that profound hypoglycaemia could produce neuronal necrosis [1] and induce distinctive patterns of neuropathological [2] and neurocognitive [3] impairment in humans who had experienced very low blood glucose levels over an extended period of time. Fortunately, most diabetic patients never experience profound hypoglycaemia. Although some writers have speculated that recurrent episodes of moderately severe hypoglycaemia could induce a less severe degree of neurocognitive dysfunction [4, 5], most recent studies of children [6] and adults [7, 8] have failed to find compelling evidence for that possibility. Taken together, these findings suggest that there is not a linear relationship between falling blood glucose levels and permanent brain dysfunction. Rather, necrotising neuronal damage occurs only after the threshold for cerebral energy failure is reached—most typically when blood glucose values fall below 1.5 mmol, and the electroencephalogram has reached an isoelectric (flat) state [9]. …