Introduction
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 2-3 years after RYGB.
METHODS
A standardized test meal (STM) was administered to all four subjects. A 2 hr hyperglycemic clamp with GLP-1 infusion during the second hr 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 hr clamp, blood glucose levels were monitored for 30 minutes. Responses were compared to a control group (5 subjects 12 mo status post RYGB without hypoglycemic symptoms).
RESULTS
During STM, both GLP-1 and insulin levels were elevated 3-4 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 minute follow-up, glucagon levels failed to rise. Due to persistent symptoms, one subject underwent 85% distal pancreatectomy; post-operatively, 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 beta cell clusters scattered throughout the acinar parenchyma was seen, as well as beta-cells present within pancreatic duct epithelium. An increase in pancreatic and duodenal homeobox-1 protein (PDX-1) expression was observed in the subject compared to 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 beta-cells is likely due to over-expression of the islet cell transcription factor, PDX-1, caused by prolonged hypersecretion of GLP-1.
The simplicity of Nova and its reliability, accuracy, and speed make it an acceptable replacement device for Beckman and YSI in the conduct of clamps, especially when perturbations require rapid glucose determination.
A concurrent subcutaneous infusion of PP enhances insulin sensitivity and reduces insulin requirements in patients with long-standing T1DM and T3cDM on insulin pump therapy. The benefit of PP infusion correlated with the degree of PP deficiency.
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