POST-HYPOGLYCEMIC HYPERKETONEMIA DOES NOT CONTRIBUTE TO BRAIN METABOLISM DURING INSULIN-INDUCED HYPOGLYCEMIA IN HUMANS

It is controversial as to whether ketone bodies are utilized by the hu man brain as a fuel alternative to glucose during hypoglycaemia. To cl arify the issue, we studied 10 normal volunteers during an experimenta l hypoglycaemia closely mimicking the clinical hypoglycaemia of patien ts with Type 1 (insulin-dependent) diabetes mellitus or insulinoma. Hy poglycaemia was induced by a continuous infusion of insulin (0.40 mU . kg-1 . min-1 for 8 h, plasma insulin almost-equal-to 180 pmol/l) whic h decreased the plasma glucose concentration to approximately 3.1 mmol /l during the last 3 h of the studies. Subjects were studied on two oc casions, i. e. spontaneous, counterregulatory-induced post-hypoglycaem ic increase in 3-beta-hydroxybutyrate (from almost-equal-to 0.2 to alm ost-equal-to 1.1 mmol/l at 8 h), or prevention of post-hypoglycaemic h yperketonaemia (plasma beta-hydroxybutyrate almost-equal-to 0.1 mmol/l throughout the study) after administration of acipimox, a potent inhi bitor of lipolysis. In the latter study, glucose was infused to match the hypoglycaemia observed in the former study. The glycaemic threshol ds and overall responses of counterregulatory hormones, symptoms (both autonomic and neuroglycopenic), and deterioration of cognitive functi on (psychomotor tests) were superimposable in the control study in whi ch ketones increased spontaneously after onset of hypoglycaemic counte rregulation, as compared to the study in which ketones were suppressed (p = NS). The fact that responses of counterregulatory hormones, symp toms and deterioration in cognitive function were not exaggerated when post-hypoglycaemic hyperketonaemia was prevented, indicate that durin g hypoglycaemia, the counterregulatory-induced endogenous hyperketonae mia does not provide the human brain with an alternative substrate to glucose. Thus, it is concluded that during hypoglycaemia, endogenous h yperketonaemia does not contribute to brain metabolism and function.