Exendin-(9-39) Effects on Glucose and Insulin in Children With Congenital Hyperinsulinism During Fasting and During a Meal and a Protein Challenge

• Published in: Diabetes care Vol. 45; no. 6; pp. 1381 - 1390
• Main Authors: Stefanovski, Darko, Vajravelu, Mary E., Givler, Stephanie, De León, Diva D.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 02.06.2022
• Subjects: Blood Glucose - metabolism; Child; Children; Congenital Hyperinsulinism - drug therapy; Cross-Over Studies; Emerging Therapies: Drugs and Regimens; Fasting; Genetic disorders; Glucose; Glucose - therapeutic use; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin resistance; Insulin, Regular, Human - therapeutic use; Laboratory testing; Pediatrics; Peptide Fragments; Postprandial Period; Proteins; Reduction; Research design
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc21-2009

The aim of this study was to assess whether exendin-(9-39) will increase fasting and postprandial plasma glucose and decrease the incidence of hypoglycemia in children with hyperinsulinism (HI). This was an open-label, four-period crossover study. In periods 1 and 2, the effect of three different dosing regimens of exendin-(9-39) (group 1, 0.28 mg/kg; group 2, 0.44 mg/kg; group 3, 0.6 mg/kg) versus vehicle on fasting glucose was assessed in 16 children with HI. In periods 3 and 4, a subset of eight subjects received either vehicle or exendin-(9-39) (0.6 mg/kg) during a mixed-meal tolerance test (MMTT) and an oral protein tolerance test (OPTT). Treatment group 2 showed 20% (P = 0.037) increase in the area under the curve (AUC) of fasting glucose. A significant increase in AUC of glucose was also observed during the MMTT and OPTT; treatment with exendin-(9-39) resulted in 28% (P ≤ 0.001) and 30% (P = 0.01) increase in AUC of glucose, respectively. Fasting AUC of insulin decreased by 57% (P = 0.009) in group 3. In contrast, AUC of insulin was unchanged during the MMTT and almost twofold higher (P = 0.004) during the OPTT with exendin-(9-39) treatment. In comparison with vehicle, infusion of exendin-(9-39) resulted in significant reduction in likelihood of hypoglycemia in group 2, by 76% (P = 0.009), and in group 3, by 84% (P = 0.014). Administration of exendin-(9-39) during the OPTT resulted in 82% (P = 0.007) reduction in the likelihood of hypoglycemia. These results support a therapeutic potential of exendin-(9-39) to prevent fasting and protein-induced hypoglycemia in children with HI.