The counterregulatory hormone responses of cortisol, growth hormone, glucagon, epinephrine, norepinephrine, and dopamine to a fixed hypoglycemic stimulus (50 mg/dl for 1 h) were studied in five type I (insulin-dependent) diabetic subjects during conventional insulin therapy (CT), after 3 mo of continuous subcutaneous insulin infusion (SC), and after 3 mo of continuous intravenous insulin infusion (IV). During the two infusion periods, the overall mean levels of preprandial blood glucose (116 ± 6 SC vs. 114 ± 5 mg/dl IV) and glycosylated hemoglobin (6.1 ± 2 SC vs. 5.9 ± 2% IV) were virtually identical, but there were more hypoglycemic episodes and greater variability of preprandial blood glucose levels during SC than with IV. During the last 30 min of the hypoglycemic clamps, the mean levels of epinephrine and cortisol were significantly lower after 3 mo of SC (epinephrine, 268 ± 80 pg/ml; cortisol, 14 ± 1 μg/dl) than with both CT (epinephrine 485 ± 80 pg/ml; cortisol, 20 ± 2 μg/dl) and IV (epinephrine, 443 ± 62 pg/ml; cortisol, 19 ± 2 μg/dl)(P < .05). The mean growth hormone level was significantly (P < .05) lower after SC (37 ± 9 ng/ml) than after IV (79 ± 12 ng/ml), but it did not reach statistical significance compared with CT (66 ± 12 ng/ml). The mean glucagon, dopamine, and norepinephrine levels during the same period of hypoglycemia were not different when all treatment regimens were compared. We conclude that intensified insulin therapy with SC leads to significant blunting of the counterregulatory hormone response to hypoglycemia, whereas IV does not. This may partly result from less frequent hypoglycemia with IV, and it may represent a therapeutic advantage of this route of insulin administration.

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