EFFECT OF ANTECEDENT HYPOGLYCEMIA ON COGNITIVE FUNCTION AND ON GLYCEMIC THRESHOLDS FOR COUNTERREGULATORY HORMONE-SECRETION IN HEALTHY HUMANS

OBJECTIVE - To determine whether reduced hormonal, symtomatic, and/or cognitive responses to hypoglycemia are caused by an increase in the p lasma glucose concentration required to stimulate these counterregulat ory parameters after antecedent hypoglycemia. RESEARCH DESIGN AND METH ODS - We studied nine healthy volunteers during stepped hypoglycemia c lamps (plasma glucose targets from 80 to 50 mg/dl in 10 mg/dl steps) o n two separate days. The study was preceded either by a 2-h period of hypoglycemia (plasma glucose 58 +/- 2 mg/dl) or a 2-h period of euglyc emia (plasma glucose 94 +/- 2 mg/dl) for 90 min. RESULTS - The plasma glucose that triggered secretion of plasma norepinephrine (NE) was low er after antecedent hypoglycemia (control = 74 +/- 2 and experimental = 67 +/- 2 mg/dl, respectively, P < 0.005). In contrast, a relatively higher plasma glucose stimulated secretion of other counterregulatory hormones after antecedent hypoglycemia: growth hormone (GH) (65 +/- 2 to 72 +/- 2 mg/dl, P < 0.01); glucagon (63 +/- 2 to 70 +/- 2 mg/dl, P < 0.01); and epinephrine (EPI) (68 +/- 2 to 76 +/- 2 mg/dl, P < 0.01) when comparing control days with experimental days. Hypoglycemic sympt oms were first observed at a plasma glucose plateau of 59 +/- 2 mg/dl. Motor function reflected by Digit Symbol Substitution deteriorated eq ually whether there had been antecedent hypoglycemia or euglycemia. Lo gical (immediate) memory deteriorated in the control study at a plasma glucose of 54 +/- 2 mg/dl but remained unchanged at equivalent hypogl ycemia in the experimental study (P < 0.03). CONCLUSIONS - Our conclus ions are as follows: 1) symptoms of moderate hypoglycemia occur at pla sma glucose levels averaging similar to 5-15 mg/dl lower than the plas ma glucose concentrations required to trigger counterregulatory hormon e release; 2) after acute antecedent hypoglycemia, glucagon, EPI, and GH secretion occur at higher plasma glucose concentrations and NE is r eleased at lower plasma glucose concentrations; and 3) there may be CN S adaptation to prior hypoglycemia reflected in preservation of logica l memory function at plasma glucose levels of similar to 50 mg/dl. The se findings suggest that thresholds for hormone secretion and for chan ges in cognitive function can be altered very acutely by foregoing hyp oglycemia in healthy humans.