Hyperinsulinemic hypoglycemia after roux-en-y gastric bypass

Unraveling the role of gut hormonal and pancreatic endocrine dysfunction

Atoosa Rabiee, J. Trent Magruder, Rocio Salas-Carrillo, Olga Carlson, Josephine M. Egan, Frederic B. Askin, Dariush Elahi, Dana Andersen

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: Profound hypoglycemia occurs rarely as a late complication after Roux-en-Y gastric bypass (RYGB). We investigated the role of glucagon-like-peptide-1 (GLP-1) in four subjects who developed recurrent neuro-glycopenia 2 to 3 y after RYGB. Methods: A standardized test meal (STM) was administered to all four subjects. A 2 h hyperglycemic clamp with GLP-1 infusion during the second hour was performed in one subject, before, during a 4 wk trial of octreotide (Oc), and after 85% distal pancreatectomy. After cessation of both glucose and GLP-1 infusion at the end of the 2 h clamp, blood glucose levels were monitored for 30 min. Responses were compared with a control group (five subjects 12 mo status post-RYGB without hypoglycemic symptoms). Results: During STM, both GLP-1 and insulin levels were elevated 3- to 4-fold in all subjects, and plasma glucose-dependent insulinotropic peptide (GIP) levels were elevated 2-fold. Insulin responses to hyperglycemia ± GLP-1 infusion in one subject were comparable to controls, but after cessation of glucose infusion, glucose levels fell to 40 mg/dL. During Oc, the GLP-1 and insulin responses to STM were reduced (>50%). During the clamp, insulin response to hyperglycemia alone was reduced, but remained unchanged during GLP-1. Glucagon levels during hyperglycemia alone were suppressed and further suppressed after the addition of GLP-1. With the substantial drop in glucose during the 30 min follow-up, glucagon levels failed to rise. Due to persistent symptoms, one subject underwent 85% distal pancreatectomy; postoperatively, the subject remained asymptomatic (blood glucose: 119-220 mg/dL), but a repeat STM showed persistence of elevated levels of GLP-1. Histologically enlarged islets, and β-cell clusters scattered throughout the acinar parenchyma were seen, as well as β-cells present within pancreatic duct epithelium. An increase in pancreatic and duodenal homeobox-1 protein (PDX-1) expression was observed in the subject compared with control pancreatic tissue. Conclusions: A persistent exaggerated hypersecretion of GLP-1, which has been shown to be insulinotropic, insulinomimetic, and glucagonostatic, is the likely cause of post-RYGB hypoglycemia. The hypertrophy and ectopic location of β-cells is likely due to overexpression of the islet cell transcription factor, PDX-1, caused by prolonged hypersecretion of GLP-1.

Original languageEnglish (US)
Pages (from-to)199-205
Number of pages7
JournalJournal of Surgical Research
Volume167
Issue number2
DOIs
StatePublished - May 15 2011
Externally publishedYes

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Glucagon-Like Peptide 1
Gastric Bypass
Hypoglycemia
Meals
Hyperglycemia
Insulin
Glucose
Pancreatectomy
Octreotide
Glucagon
Islets of Langerhans
Blood Glucose
Gastric Inhibitory Polypeptide
Pancreatic Ducts
Hypoglycemic Agents
Hypertrophy
Transcription Factors
Epithelium

Keywords

  • bariatric surgery
  • GLP-1
  • glucagons
  • hyperinsulinemia
  • hypoglycemia
  • Roux-en-Y

ASJC Scopus subject areas

  • Surgery

Cite this

Hyperinsulinemic hypoglycemia after roux-en-y gastric bypass : Unraveling the role of gut hormonal and pancreatic endocrine dysfunction. / Rabiee, Atoosa; Magruder, J. Trent; Salas-Carrillo, Rocio; Carlson, Olga; Egan, Josephine M.; Askin, Frederic B.; Elahi, Dariush; Andersen, Dana.

In: Journal of Surgical Research, Vol. 167, No. 2, 15.05.2011, p. 199-205.

Research output: Contribution to journalArticle

Rabiee, Atoosa ; Magruder, J. Trent ; Salas-Carrillo, Rocio ; Carlson, Olga ; Egan, Josephine M. ; Askin, Frederic B. ; Elahi, Dariush ; Andersen, Dana. / Hyperinsulinemic hypoglycemia after roux-en-y gastric bypass : Unraveling the role of gut hormonal and pancreatic endocrine dysfunction. In: Journal of Surgical Research. 2011 ; Vol. 167, No. 2. pp. 199-205.
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abstract = "Background: Profound hypoglycemia occurs rarely as a late complication after Roux-en-Y gastric bypass (RYGB). We investigated the role of glucagon-like-peptide-1 (GLP-1) in four subjects who developed recurrent neuro-glycopenia 2 to 3 y after RYGB. Methods: A standardized test meal (STM) was administered to all four subjects. A 2 h hyperglycemic clamp with GLP-1 infusion during the second hour was performed in one subject, before, during a 4 wk trial of octreotide (Oc), and after 85{\%} distal pancreatectomy. After cessation of both glucose and GLP-1 infusion at the end of the 2 h clamp, blood glucose levels were monitored for 30 min. Responses were compared with a control group (five subjects 12 mo status post-RYGB without hypoglycemic symptoms). Results: During STM, both GLP-1 and insulin levels were elevated 3- to 4-fold in all subjects, and plasma glucose-dependent insulinotropic peptide (GIP) levels were elevated 2-fold. Insulin responses to hyperglycemia ± GLP-1 infusion in one subject were comparable to controls, but after cessation of glucose infusion, glucose levels fell to 40 mg/dL. During Oc, the GLP-1 and insulin responses to STM were reduced (>50{\%}). During the clamp, insulin response to hyperglycemia alone was reduced, but remained unchanged during GLP-1. Glucagon levels during hyperglycemia alone were suppressed and further suppressed after the addition of GLP-1. With the substantial drop in glucose during the 30 min follow-up, glucagon levels failed to rise. Due to persistent symptoms, one subject underwent 85{\%} distal pancreatectomy; postoperatively, the subject remained asymptomatic (blood glucose: 119-220 mg/dL), but a repeat STM showed persistence of elevated levels of GLP-1. Histologically enlarged islets, and β-cell clusters scattered throughout the acinar parenchyma were seen, as well as β-cells present within pancreatic duct epithelium. An increase in pancreatic and duodenal homeobox-1 protein (PDX-1) expression was observed in the subject compared with control pancreatic tissue. Conclusions: A persistent exaggerated hypersecretion of GLP-1, which has been shown to be insulinotropic, insulinomimetic, and glucagonostatic, is the likely cause of post-RYGB hypoglycemia. The hypertrophy and ectopic location of β-cells is likely due to overexpression of the islet cell transcription factor, PDX-1, caused by prolonged hypersecretion of GLP-1.",
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AU - Elahi, Dariush

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