Hypoglycemic symptom variation is related to epinephrine and not peripheral muscle sympathetic nerve response

Hypoglycemic unawareness may be due to diminished adrenal and/or peripheral sympathochromaffin responses to hypoglycemia. To determine whether hypoglycemic symptom awareness is more closely related to adrenal or nonadrenal sympathetic activity, we studied the relationship between symptoms and the epinephrine, norepinephrine, and muscle sympathetic nerve activity (MSNA) responses to hypoglycemia in ten IDDM and ten control subjects. MSNA was measured continuously using microneurography during hyperinsulinemic (720 pmol m-2 min-1), glucose clamp with 60 min of euglycemia, 30 min of hypoglycemia, and 30 min of recovery. Subjects were asked to rate a series of symptoms every 10 min during the last 30 min of each period and were unaware of their plasma glucose concentration. MSNA increased significantly in both groups during insulin clamp (p < 0.05) and further increased during hypoglycemia (p < 0.01). Both epinephrine and norepinephrine levels significantly increased during hypoglycemia (p < 0.02). The increase in adrenergic symptom responses during hypoglycemia positively correlated with epinephrine (r = 0.75, p < 0.01), but not with MSNA in the control subjects. A similar near significant relationship for epinephrine was seen in IDDM subjects (r = 0.65, p = 0.056). No significant predictors were found for neuroglycopenic or cholinergic symptoms. Thus, the variation in hypoglycemic symptoms is not related to the MSNA response to hypoglycemia. Adrenergic symptom variation is due to differences in adrenal epinephrine secretion.