Background:
Congenital hyperinsulinism (CHI), a
rare disease of excessive and dysregulated insulin secretion, can lead to prolonged and severe
hypoglycemia.
Dextrose infusions are a mainstay of
therapy to restore normal glycemia, but can be associated with volume overload, especially in infants. By releasing intrahepatic
glucose stores,
glucagon infusions can reduce dependency on
dextrose infusions. Recent studies have reported positive outcomes with
glucagon infusions in patients with CHI; however, to date, there are no reports describing the clinical utility of titrated doses of infused
glucagon to achieve glycemic stability. Objective: To assess the potential clinical utility of dose-titrated
glucagon infusions in stabilizing glycemic status in pediatric patients with CHI, who were managed by medical and/or surgical approaches. Methods: Patients with CHI (N = 33), with or without mutations in the
ATP-sensitive K+ channel genes, ABCC8, and KCNJ11 requiring
glucagon by dose titration in addition to intravenous
dextrose and medical
therapy with
diazoxide/
octreotide to achieve glycemic stability were recruited. Following
glucagon titration and a 24-h
glucose stable period,
glucose infusion rate (GIR) was reduced over a 24-h period. Achievement of glycemic stability and decrease in GIR were considered end points of the study. Results: All patients achieved glycemic stability with
glucagon infusion, demonstrating clinical benefit. GIR reduced from 15.6 (4.5) to 13.4 (4.6) mg/kg/min mean (SD) (p = 0.00019 for difference; n = 32; paired t-test) over 24 h. By univariate analysis, no individual baseline characteristic was associated with changes in the GIR. However, by baseline-adjusted modeling, mutational status of the patient (p = 0.011) was inversely associated with a reduction in GIR. Adverse events were infrequent with
diarrhea possibly attributed to
glucagon treatment in 1 patient. With long-term treatment following GIR reduction,
necrolytic migratory erythema was observed in another patient. Conclusion: These data suggest that dose-titrated
glucagon infusion
therapy aids hypoglycemia prevention and reduction in GIR in the clinical management of patients with CHI.