Postprandial Hypoglycemia in Children after Gastric Surgery: Clinical Characterization and Pathophysiology

Abstract

Background/Aims: Dumping syndrome is a common complication in children after fundoplication and other gastric surgeries and is characterized by postprandial hypoglycemia (PPH). Children with PPH have an exaggerated GLP-1 response to a meal with an exaggerated insulin surge and subsequent hypoglycemia. We evaluated the role of GLP-1 in the pathogenesis of PPH by examining the effects of GLP-1 receptor blockade on glucose and insulin response to a meal. Methods: Six children with known PPH after surgery underwent a mixed meal tolerance test with/without the GLP-1 receptor antagonist exendin-(9-39) using an open-label crossover design. Results: Average nadir plasma glucose concentration was ≥65 mg/dl in all treatment conditions; however, 3 out of the 6 subjects had a nadir plasma glucose <65 mg/dl during vehicle infusion, while only 1 out of the 6 had a nadir plasma glucose <65 mg/dl during infusion of exendin-(9-39). Exendin-(9-39) suppressed postmeal insulin concentrations when compared to vehicle, with a lower peak insulin concentration observed in the children who received 500 pmol/kg/min of exendin-(9-39) (131.3 ± 125.1 pmol/l) compared to children who received 300 pmol/kg/min (231.1 ± 153.4 pmol/l) or vehicle (259.7 ± 120.2 pmol/l). Gastric emptying was not different between groups. Conclusion: Our results suggest that the exaggerated insulin response to a meal is at least in part due to the effects of GLP-1 on the pancreatic β-cell and suggest that GLP-1 receptor antagonists may represent a potential avenue of treatment for children with PPH.

Post-Prandial Hyperinsulinaemic Hypoglycaemia after Oesophageal Surgery in Children

“…The pathogenesis is likely related to the early development of hyperinsulinaemic (reactive) hypoglycaemia [1]. Calabria et al [2] demonstrated that the exaggerated insulin response to a meal, seen in children with post-prandial hypoglycaemia after gastric surgery, is at least in part due to the effects of GLP-1 on the pancreatic β-cell, as the blockade of the GLP-1 receptor with exendin (9–39) blunted the insulin response even in the presence of hyperglycaemia.…”

“…Montgomery et al [8] showed a delayed gastric emptying in patients who have repaired oesophageal atresia. Meanwhile, the role of GLP-1 that was proved to play a key role in PPHH in children after gastric surgery [2] needs to be investigated in children with PPHH following oesophageal atresia repair. Children with PPHH can present either acutely, with life-threatening symptoms such as hypoglycaemic seizures, or they could be asymptomatic.…”

“…PPHH is a recognized complication observed after a variety of gastric surgical procedures such as vagotomy, pyloroplasty, gastrojejunostomy, and laparoscopic Nissen fundoplication [1, 2]. …”

“…In childhood, the surgical treatment of gastro-oesophageal reflux by gastric fundoplication is the main cause of PPHH [2-5]. PPHH after oesophageal atresia repair without anti-reflux surgery is rare.…”

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations

“…The gastric fundoplication wraps around a main branch of the vagus nerve; whether gastric motility worsens post-surgery due to vagal nerve injury is unknown but plausible [24]. Other potential side effects of fundoplication include dumping syndrome, worsening of esophageal motility, and the “gas-bloat syndrome” [69, 70]. There are data to suggest that the presence of a fundoplication may increase the risk of gastrointestinal bleeding [71].…”