Increased Glucagon-Like Peptide-1 Secretion and Postprandial Hypoglycemia in Children after Nissen Fundoplication

The Children's Hospital of Philadelphia, Abramson Research Center, Room 802A, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 10/2008; 94(1):39-44. DOI: 10.1210/jc.2008-1263
Source: PubMed


Postprandial hypoglycemia (PPH) is a frequent complication of Nissen fundoplication in children. The mechanism responsible for the PPH is poorly understood, but involves an exaggerated insulin response to a meal and subsequent hypoglycemia. We hypothesize that increased glucagon-like peptide-1 (GLP-1) secretion contributes to the exaggerated insulin surge and plays a role in the pathophysiology of this disorder.
The aim of the study was to characterize glucose, insulin, and GLP-1 response to an oral glucose load in children with symptoms of PPH after Nissen fundoplication.
Ten patients with suspected PPH and a history of Nissen fundoplication and eight control subjects underwent a standard oral glucose tolerance test at The Children's Hospital of Philadelphia. Blood glucose (BG), insulin, and intact GLP-1 levels were obtained at various time points.
Children ages 4 months to 13 years old were studied.
Change scores for glucose, insulin, and intact GLP-1 were recorded after an oral glucose tolerance test.
All cases had hypoglycemia after the glucose load. Mean BG at nadir (+/- sd) was 46.7 +/- 11 mg/dl for cases (vs. 85.9 +/- 21.3 mg/dl; P < 0.0005). Mean change in BG from baseline to peak (+/- sd) was 179.3 +/- 87.4 mg/dl for cases (vs. 57.8 +/- 39.5 mg/dl; P = 0.003). Mean change in BG (+/- sd) from peak to nadir was 214.4 +/- 85.9 mg/dl for cases (vs. 55.9 +/- 41.1 mg/dl, P < 0.0005). Mean change in insulin (+/- sd) from baseline to peak was 224.3 +/- 313.7 microIU/ml for cases (vs. 35.5 +/- 22.2 microIU/ml; P = 0.012). Mean change in GLP-1 (+/- sd) from baseline to peak was 31.2 +/- 24 pm (vs. 6.2 +/- 9.5 pm; P = 0.014).
Children with PPH after Nissen fundoplication have abnormally exaggerated secretion of GLP-1, which may contribute to the exaggerated insulin surge and resultant hypoglycemia.

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Available from: Samir Sayed, Oct 14, 2015
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    • "It has also been observed in adult patients who have undergone gastric bypass surgery for morbid obesity.[69] It has been noted that children with PPHH after Nissen fundoplication have abnormally exaggerated secretion of glucagon like peptide-1 (GLP-1) which may contribute to the exaggerated insulin surge and resultant hypoglycemia.[70] PPHH is also observed in the insulin autoimmune syndrome which is characterized by the presence of insulin-binding autoantibodies in subjects who have not been previously exposed to exogenous insulin.[71] "
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    ABSTRACT: Congenital hyperinsulinism (CHI) is the result of unregulated insulin secretion from the pancreatic β-cells leading to severe hypoglycaemia. In these patients it is important to make an accurate diagnosis and initiate the appropriate management so as to avoid hypoglycemic episodes and prevent the potentially associated complications like epilepsy, neurological impairment and cerebral palsy. At a genetic level abnormalities in eight different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) have been reported with CHI. Loss of function mutations in ABCC8/KCNJ11 lead to the most severe forms of CHI which are usually medically unresponsive. At a histological level there are two major subgroups, diffuse and focal, each with a different genetic etiology. The focal form is sporadic in inheritance and is localized to a small region of the pancreas whereas the diffuse form is inherited in an autosomal recessive (or dominant) manner. Imaging using a specialized positron emission tomography scan with the isotope fluroine-18 L-3, 4-dihydroxyphenyalanine (18F-DOPA-PET-CT) is used to accurately locate the focal lesion pre-operatively and if removed can cure the patient from hypoglycemia. Understanding the molecular mechanisms, the histological basis, improvements in imaging modalities and surgical techniques have all improved the management of patients with CHI.
    03/2013; 17(1):19-30. DOI:10.4103/2230-8210.107822
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    • "Precipitous emptying of hyperosmolar carbohydrate-containing solutions into the small bowel shifts fluid into the bowel lumen,which results in hypovolaemia, rapid glucose absorption, hyperglycaemia, and reactive hypoglycaemia. It has been noted that children with postprandial HH after Nissen’s fundoplication have abnormally exaggerated secretion of glucagon-like peptide-1 (GLP-1), which may contribute to the exaggerated insulin surge and resultant hypoglycaemia (75). "
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    ABSTRACT: Hyperinsulinaemic hypoglycaemia (HH) is characterized by unregulated insulin secretion from pancreatic β-cells. Untreated hypoglycaemia in infants can lead to seizures, developmental delay, and subsequent permanent brain injury. Early identification and meticulous managementof these patients is vital to prevent neurological insult. Mutations in eight different genes (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1, HNF4A and UCP2) have been identified to date in patients with congenital forms of hyperinsulinism (CHI). The most severe forms of CHI are due to mutations in ABCC8 and KCJN11, which encode the two components of pancreatic β-cell ATP-sensitive potassium channel. Recent advancement in understanding the genetic aetiology, histological characterisation into focal and diffuse variety combined with improved imaging (such as fluorine 18 L-3, 4-dihydroxyphenylalanine positron emission tomography 18F-DOPA-PET scanning) and laparoscopic surgical techniques have greatly improved management. In adults, HH can be due to an insulinoma, pancreatogenous hypoglycaemic syndrome, post gastric-bypass surgery for morbid obesity as well as to mutations in insulin receptor gene. This review provides an overview of the molecular basis of CHI and outlines the clinical presentation, diagnostic criteria, and management of these patients. Conflict of interest:None declared.
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    • "Genetic and pharmacologic disruption of GLP-1 receptor signaling leads to fasting hyperglycemia (4–10), suggesting that in addition to contributing to postprandial glucose regulation, GLP-1 plays a role in the control of fasting glucose. Exendin-(9-39), a truncated form of the GLP-1 agonist exendin-4, is a specific GLP-1 receptor antagonist in mice and humans (5,11,12). In preclinical studies, we showed that exendin-(9-39) decreases cAMP levels and insulin secretion in SUR-1−/− mouse islets (13). "
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