ANTECEDENT INSULIN LEVEL AND PATTERN OF INDUCTION OF ACUTE HYPOGLYCEMIA DO NOT AFFECT SUBSEQUENT COUNTERREGULATORY RESPONSES IN HEALTHY-SUBJECTS

1. This study was designed to determine whether the duration and patte rn of prior insulin exposure modulate the symptomatic and counterregul atory responses to hypoglycaemia. 2. Ten healthy non-obese subjects (f ive males/five females age 25+/-1 years, mean+/-SEM) were made hypogly caemic in three ways: (i) a hyperinsulinaemic (60 m-units min-1 m-2; p lasma insulin concentration 95 m-units/l) clamp, with 1 h of euglycaem ia, blood glucose level 4.5 mmol/l, followed by 30min of hypoglycaemia , at a stable glucose nadir of 2.0 mmol/l (i.e. euglycaemic then hypog lycaemic clamp: E+HC); (ii) an identical hypoglycaemic clamp without p receding hyperinsulinaemic euglycaemia (i.e. a hypoglycaemic clamp: HC ); (iii) insulin infusion only, discontinued at a blood glucose level of 3.0 mmol/l (II). Blood glucose level reached the same nadir as on E +HC and HC, and did not fall further. At the glucose nadir, and 15 and 30 min after, the plasma insulin concentration was 23, 7 and 4 m-unit s/l, respectively, on the II visit. 3. At the glucose nadir, plasma gl ucagon level, plasma adrenaline level, sweating rate, heart rate, bloo d pressure, and overall and individual symptom scores (using visual an alogue scales) were the same on E+HC, HC and II. 4. There were no sign ificant differences in neurohormonal response between E+HC and HC, but more subjects felt hypoglycaemic on E+HC on arrival at the glucose na dir (P<0.05). There was significantly more blurring of vision (1.3+0.5 versus 0.2+0.1 cm) and tingling (1.2+0.4 versus 0.2+0.1 cm) 30 min af ter arriving at the glucose nadir on E+HC than HC (P<0.05, analysis of variance). 5. Significant differences were only found between E+HC or HC and the II visit 15 min after arriving at the glucose nadir, when the blood glucose level had risen significantly to 2.9 mmol/l, and 30 min after arrived at the glucose nadir, by which time the blood glucos e level had recovered to 3.8 mmol/l. 6. A 1 h run-in period of euglyca emic hyperinsulinaemia does not affect the hormonal or physiological r esponse to an identical degree of hypoglycaemia, but appears to cause increased symptoms of neuroglycopenia during subsequent stable hypogly caemia. 7. A difference in plasma insulin level within the physiologic al range does not affect the magnitude of symptomatic, hormonal or phy siological responses to the same degree of hypoglycaemia.