RELATIVE ROLES OF INSULIN AND HYPOGLYCEMIA ON INDUCTION OF NEUROENDOCRINE RESPONSES TO, SYMPTOMS OF, AND DETERIORATION OF COGNITIVE FUNCTION IN HYPOGLYCEMIA IN MALE AND FEMALE HUMANS

To assess the relative roles of insulin and hypoglycaemia on induction of neuroendocrine responses, symptoms and deterioration of cognitive function (12 cognitive tests) during progressive decreases in plasma g lucose, and to quantitate glycaemic thresholds, 22 normal, non-diabeti c subjects (11 males, 11 females) were studied on four occasions: prol onged fast (n = 8, saline euglycaemia study, SA-EU), stepped hypoglyca emia (plasma glucose plateaus of 4.3, 3.7, 3 and 2.3 mmol/l) or euglyc aemia during insulin infusion at 1 and 2 mU.kg(-1).min(-1) (n = 22, hi gh-insulin hypoglycaemia and euglycaemia studies, HI-INS-HYPO and HI-I NS-EU, respectively), and stepped hypoglycaemia during infusion of ins ulin at 0.35 mU.kg(-1).min(-1) (n =9, low-insulin hypoglycaemia study, LO-INS-HYPO). Insulin per se (SA-EU vs HI-INS-EU), suppressed plasma glucagon (similar to 20%) and pancreatic polypeptide (similar to 30 %) , whereas it increased plasma noradrenaline (similar to 10%, p < 0.05) . Hypoglycaemia per se (HI-INS-HYPO vs HI-INS-EU) induced responses of counterregulatory hormones (CR-HORM), symptoms and deteriorated cogni tive function. With the exception of suppression of endogenous insulin secretion, which had the lowest glycaemic threshold of 4.44 +/- 0.06 mmol/l, pancreatic polypeptide, glucagon, growth hormone, adrenaline a nd cortisol had similar glycaemic thresholds (similar to 3.8-3.6 mmol/ l); noradrenaline (3.1 +/- 0.0 mmol/l), autonomic (3.05 +/- 0.06 mmnol /l) and neuroglycopenic (3.05 +/- 0.05 mmol/l) symptoms had higher thr esholds. All 12 tests of cognitive function deteriorated at a glycaemi c threshold of 2.45 +/- 0.06 mmol/l, but 7 out of 12 tests were alread y abnormal at a glycaemic threshold of 2.89 +/- 0.06 mmol/l. Although all CR-HORM had a similar glycaemic threshold, the lag time of respons e (the time required for a given parameter to increase) of glucagon (1 5 +/- 1 min) and growth hormone (14 +/- 3 min) was shorter than adrena line (19 +/- 3 min) and cortisol (39 +/- 4 min) (p < 0.05). With the e xception of glucagon (which was suppressed) and noradrenaline (which w as stimulated), insulin per se (HI-INS-HYPO vs LO-INS-HYPO) did not af fect the responses of CR-HORM, and did not influence the symptoms or t he cognitve function during hypoglycaemia. Despite lower responses of glucagon, adrenaline and growth hormone (but not thresholds) in female s than males, females were less insulin sensitive than males during st epped hypoglycaemia.