Efficacy of Dose-Titrated Glucagon Infusions in the Management of Congenital Hyperinsulinism: A Case Series
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...
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| Format: | Article |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2020.00441/full |
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| author | Maria Salomon-Estebanez Daphne Yau Mark J. Dunne Chris Worth Sune Birch José L. Walewski Indraneel Banerjee Indraneel Banerjee |
| author_facet | Maria Salomon-Estebanez Daphne Yau Mark J. Dunne Chris Worth Sune Birch José L. Walewski Indraneel Banerjee Indraneel Banerjee |
| author_sort | Maria Salomon-Estebanez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T16:17:10Z |
| format | Article |
| id | doaj.art-f85e3c68ed3545579ba6af3d5cfe5e36 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-19T16:17:10Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-f85e3c68ed3545579ba6af3d5cfe5e362022-12-21T20:14:35ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-09-011110.3389/fendo.2020.00441547703Efficacy of Dose-Titrated Glucagon Infusions in the Management of Congenital Hyperinsulinism: A Case SeriesMaria Salomon-Estebanez0Daphne Yau1Mark J. Dunne2Chris Worth3Sune Birch4José L. Walewski5Indraneel Banerjee6Indraneel Banerjee7Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, United KingdomDepartment of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomDepartment of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, United KingdomDepartment of Statistics, Zealand Pharma A/S, Søborg, DenmarkMedical Publications, rareLife Solutions, Norwalk, CT, United StatesDepartment of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomBackground: 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.https://www.frontiersin.org/article/10.3389/fendo.2020.00441/fullglucosecongenital hyperinsulinismhypoglycemiaglucagoninfusiondose titration |
| spellingShingle | Maria Salomon-Estebanez Daphne Yau Mark J. Dunne Chris Worth Sune Birch José L. Walewski Indraneel Banerjee Indraneel Banerjee Efficacy of Dose-Titrated Glucagon Infusions in the Management of Congenital Hyperinsulinism: A Case Series Frontiers in Endocrinology glucose congenital hyperinsulinism hypoglycemia glucagon infusion dose titration |
| title | Efficacy of Dose-Titrated Glucagon Infusions in the Management of Congenital Hyperinsulinism: A Case Series |
| title_full | Efficacy of Dose-Titrated Glucagon Infusions in the Management of Congenital Hyperinsulinism: A Case Series |
| title_fullStr | Efficacy of Dose-Titrated Glucagon Infusions in the Management of Congenital Hyperinsulinism: A Case Series |
| title_full_unstemmed | Efficacy of Dose-Titrated Glucagon Infusions in the Management of Congenital Hyperinsulinism: A Case Series |
| title_short | Efficacy of Dose-Titrated Glucagon Infusions in the Management of Congenital Hyperinsulinism: A Case Series |
| title_sort | efficacy of dose titrated glucagon infusions in the management of congenital hyperinsulinism a case series |
| topic | glucose congenital hyperinsulinism hypoglycemia glucagon infusion dose titration |
| url | https://www.frontiersin.org/article/10.3389/fendo.2020.00441/full |
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