Hypoglycaemia in Clinical Diabetes

CEREBRAL ADAPTATION 179hypoglycaemia. It is becoming evident that changes in symptomatic responses and corticalfunction in hypoglycaemia are driven by complex mechanisms associated with, but notexclusively controlled directly by, the changes in the glucose metabolic rate of neurones.Some cognitive functions are better preserved than others during hypoglycaemia in subjectswho have previous experience of hypoglycaemia than in hypoglycaemia-naive subjects whohave normal counterregulation (Fanelli et al., 1993; Boyle et al., 1995). This does not entirelyfit the clinical picture of patients becoming significantly confused during hypoglycaemiawhile remaining asymptomatic.One measure of cognitive function, the choice reaction time, does not appear to adapt, andwhen hypoglycaemia is induced slowly, it deteriorates at similar levels of blood glucose inmost subjects, irrespective of their previous glycaemic experience and their state of hypoglycaemiaawareness (Maran et al., 1995). Other measures of cognitive function also deteriorateat similar levels of blood glucose in diabetic subjects who have had very disparate experiencesof preceding glycaemia (Widom and Simonson, 1990; Amiel et al., 1991; Hvidberget al., 1996). The ability of the brain to adapt its metabolic and functional capacity accordingto previous glycaemic experience varies across different regions of the brain. Regions of thebrain that detect hypoglycaemia, and some parts of the cerebral cortex, may be able to adaptmore effectively to antecedent hypoglycaemia than other areas, to sustain glucose metabolismduring subsequent exposure. As blood glucose falls this would effectively destroy the normalprotective hierarchy of corrective and symptomatic responses that precede cognitive impairment,replacing it with the dangerous situation whereby cognitive impairment is the initialresponse to hypoglycaemia, with autonomic responses not occurring until the blood glucosedeclines to a much lower level. In this situation the patient becomes too confused and unableto recognise the warning symptoms and so take appropriate corrective action (Figure 8.3).Figure 8.3 The change in hierarchy of responses to hypoglycaemia (a) before and (b) after intensifiedinsulin therapy in type 1 diabetes mellitus