Hypoglycemia unawareness is thought to be the consequence of recurrent
hypoglycemia, yet the underlying mechanism is still incompletely understood. The aim of the present study was to determine the role of antecedent elevated
adrenaline in the pathogenesis of
hypoglycemia unawareness. Sixteen healthy volunteers (eight of either sex) participated in two experiments, performed in random order and at least 3 wk apart. During the morning, three consecutive doses of 0.04, 0.06, and 0.08 microg.kg(-1).min(-1) of
adrenaline or matching placebo (
normal saline) were infused for the total duration of 1 h. Three hours later, a hyperinsulinemic (360 pmol.m(-2).min(-1)) two-step
hypoglycemic (5.0-3.5-2.5 mmol.liter(-1)) clamp study was performed. During
hypoglycemia,
hypoglycemic symptoms, counterregulatory
hormones, cardiovascular responses, and cognitive function were monitored.
Hypoglycemia induced similar responses of autonomic and neuroglycopenic symptoms, counterregulatory
hormones, and lengthening in reaction time on the choice reaction time task, irrespective of antecedent infusions. However, prior
adrenaline was associated with higher exogenous
glucose requirements at
hypoglycemic nadir (10.1 +/- 1.3 vs. 7.3 +/- 1.3 micromol.kg(-1).min(-1), P = 0.017), an attenuated
hypoglycemia-induced fall in blood pressure (mean arterial pressure, -13 +/- 2 vs. -8 +/- 2 mm Hg, P = 0.006), and preserved cognitive function as assessed by the symbol digit test during
hypoglycemia, when compared with prior placebo. We conclude that elevated
adrenaline attenuates the responsiveness to, but not the release of counterregulatory
hormones during subsequent
hypoglycemia. As such,
adrenaline's role in the development of
hypoglycemia unawareness is limited.