Acute metabolic effects of exenatide in patients with Type 1 Diabetes with and without residual insulin to oral and IV glucose challenges

  1. Kevan C Herold, MD1
  1. 1Departments of Immunobiology and Internal Medicine, Yale University School of Medicine, New Haven, CT, 06520
  2. 2Department of Pediatrics, Yale University School of Medicine, New Haven, CT
  1. Address of corresponding author: Kevan C. Herold, Email: kevan.herold{at}yale.edu

Abstract

Objective Glucagon-like peptide-1 (GLP-1) is an incretin hormone, released from the GI-tract. Treatment with GLP-1 analogs has proven to be of clinical use for patients with Type 2 diabetes. Patients with Type 1 diabetes, particularly those with residual β-cell function, may also respond to treatment, but the acute metabolic effects of GLP-1 analogs in these patients to both oral and IV glucose challenges are not well understood.

Research Design and Methods Seventeen patients with type 1 diabetes, half of whom had residual insulin production, underwent two mixed meal tolerance tests (MMTT) and two intravenous glucose tolerance tests (IVGTT), with and without pretreatment with exenatide. No exogenous bolus insulin was administered for the studies. Glucose excursions, insulin secretion rates (ISR), glucagon, endogenous GLP-1, and GIP levels were measured following the meal or glucose loads.

Results During the MMTT, glucose levels were suppressed with exenatide in patients with or without residual insulin production (p=0.0003). Exenatide treatment did not change the absolute ISR but the ISR to glucose levels were increased (p=0.0078). Gastric emptying was delayed (p=0.0017) and glucagon was suppressed (p=0.0015). None of these hormonal or changes in glucose were detected during the IVGTT with exenatide administration.

Conclusion Exenatide showed a significant antidiabetogenic effect prior to an oral meal in patients with type 1 diabetes involving glucagon suppression and gastric emptying, while preserving increased insulin secretion. GLP-1 analogs may be useful as an adjunctive treatment in Type 1 diabetes.

  • Received May 16, 2013.
  • Accepted August 5, 2013.

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This Article

  1. Diabetes Care
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