Impaired counterregulation of hypoglycemia in insulin-dependent diabetes mellitus

We evaluated the recovery of blood glucose after insulin-induced hypoglycemia in six insulin-dependent diabetics (insulin-infused and initially euglycemic) and six normal controls after comparable reductions in plasma glucose. In contrast to controls, the recovery of plasma glucose was delayed in diabetics (2-h plasma glucose 80 ± 5 mg/dl and 58 ± 5 mg/dl, respectively, P < 0.01). This delay was due to the absence of a rebound in hepatic glucose output n the diabetics, whereas glucose output rose two- to threefold above baseline in normals. The impaired rebound in glucose output in diabetics could not be attributed to hyperinsulinemia. Rather, hypoglycemia-induced secretion of epinephrine and glucagon was reduced in the diabetics by 60-80% as compared with normals (P < 0.001). The diabetics did not suffer from overt neuropathy and plasma cortisol, growth hormone, and norepinephrine increased normally following hypoglycemia. The data suggest that prolonged hypoglycemia may frequently occur in tightly controlled type I diabetics because of impaired rebound in hepatic glucose release which in turn may be a consequence of reduced secretion of epinephrine and glucagon.