To determine whether immature or defective glucose counterregulation was responsible for the severe recurrent hypoglycemic episodes (3.6 per patient per year) observed during conventional therapy (CT) in six pre-school-age diabetic children, we investigated their metabolic and hormonal responses to insulin infusion (40 mU/kg i.v. for 60 min). Counterregulation was considered adequate because no patient experienced symptoms requiring discontinuation of the test, and blood glucose (BG) nadirs averaged 42 ± 5 mg/dl. Glucose production rate decreased from 4.2 ± 0.2 to 2.6 ± 0.6 mg · kg−1 · min−1. Blood 3-hydroxybutyrate levels were elevated (∼ 3 mM) and did not change during insulin infusion. The responses of epinephrine (from 137 ± 37 to 393 ± 143 pg/ml), norepinephrine (from 145 ± 33 to 347 ± 152 pg/ml), and growth hormone (from 6.0 ± 1.5 to 20.3 ± 5.1 ng/ml) were normal for this age group. As previously observed in diabetic adults, glucagon response was deficient (from117 ± 30 to 114 ± 18 pg/ml). The six children were subsequently treated with continuous subcutaneous insulin infusion (CSII), which resulted in a 20-fold decrease in the number of severe hypoglycemic reactions. Predisposition to severe hypoglycemia in this subset of diabetic children, which remains a refractory problem even after considerable efforts have been made to decrease them, may thus be sharply decreased with CSII therapy. During this therapy, a significant inverse correlation appeared between the individual frequency of BG values <40 mg/dl and BG nadir during the insulin infusion test (r = .94, P < .001). We conclude that the glucose counterregulatory status evaluated by a simple standardized insulin- infusion test can predict the risk of developing hypoglycemia during CSII in young diabetic children, as proposed previously in adults.

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