Glucose counterregulation in pre-school-age diabetic children with recurrent hypoglycemia during conventional treatment.

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 X kg-1 X min-1. Blood 3-hydroxybutyrate levels were elevated (approximately 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 (from 117 +/- 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 less than 40 mg/dl and BG nadir during the insulin infusion test (r = .94, P less than .001).