Influence of counterregulatory hormones, independently of hypoglycaemia, on cognitive function, warning symptoms and glucose kinetics.

1. To assess the influence of counterregulatory hormones, independently of neuroglycopaenia, on higher cerebral (cognitive) function, 'hypoglycaemic' warning symptoms and glucose kinetics, 10 healthy subjects participated in two hyperinsulinaemic (2 m-units min-1 kg-1) glucose clamp studies. After 100 min of euglycaemia (plasma glucose level 5 mmol/l), the plasma glucose level was either (a) maintained at 5 mmol/l for 120 min by glucose infusion with concomitant replacement of counterregulatory hormones (continuous infusions of glucagon, adrenaline, noradrenaline, cortisol and growth hormone) to mimic the hormonal milieu normally associated with hypoglycaemia (hormone infusion study) or (b) lowered to 2.8 mmol/l for 120 min (hypoglycaemia study). Assessments were made of cognitive function (P300 auditory evoked responses), symptoms (visual analogue scales) and glucose kinetics (3-[3H]glucose). 2. Hypoglycaemia was associated with an increase in all symptoms (facial flushing, palpitations, tingling, trembling, sweating, hunger, light-headedness and sleepiness, P < 0.01) and all subjects were aware that blood glucose levels had fallen. P300 evoked potential latency increased from 280 +/- 6 to 312 +/- 5 ms (mean +/- SEM, P < 0.01). In contrast, P300 latency and several individual symptoms (hunger, facial flushing, sweating and light-headedness) did not change from baseline during the hormone infusion study (P < 0.05 versus hypoglycaemia). Hepatic glucose production was lower (1.5 +/- 0.4 versus 2.3 +/- 0.3 mg min-1 kg-1, P < 0.05) and peripheral glucose uptake was higher (7.4 +/- 1.0 versus 5.6 +/- 0.6 mg min-1 kg-1, P < 0.01) during infusion of the hormones compared with during hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)