Hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass: unraveling the role of gut hormonal and pancreatic endocrine dysfunction.

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.

• Authors: Atoosa Rabiee, J Trent Magruder, Rocio Salas-Carrillo, Olga Carlson, Josephine M Egan, Frederic B Askin, Dariush Elahi, Dana K Andersen
• Journal: The Journal of surgical research (J Surg Res) Vol. 167 Issue 2 Pg. 199-205 (May 15 2011) ISSN: 1095-8673 [Electronic] United States
• PMID: 21414635 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Homeodomain Proteins
• Insulin
• Trans-Activators
• pancreatic and duodenal homeobox 1 protein
• Gastric Inhibitory Polypeptide
• Glucagon-Like Peptide 1
• Glycogen

Topics

• Blood Glucose (metabolism)
• Endocrine System (physiopathology)
• Female
• Gastric Bypass (adverse effects)
• Gastric Inhibitory Polypeptide (metabolism)
• Gastrointestinal Tract (physiopathology)
• Glucagon-Like Peptide 1 (metabolism, pharmacology)
• Glycogen (metabolism)
• Homeodomain Proteins (metabolism)
• Humans
• Hyperinsulinism (etiology, physiopathology)
• Hypoglycemia (etiology, physiopathology)
• Insulin (metabolism)
• Middle Aged
• Obesity (surgery)
• Pancreas (physiopathology)
• Trans-Activators (metabolism)