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Submitted on May 16, 2005
Accepted on August 26, 2005
Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany; Eli Lilly & Co., Hamburg, Germany, and Indianapolis, Indiana, USA; Dept. Medical Physiology, Panum Institute, Univ. Copenhagen, Blegdansve 3, DK- 2200 Copenhagen N, Denmark; Amylin Pharmaceuticals, San Diego, California, USA
* To whom correspondence should be addressed. E-mail: loretta.nielsen{at}amylin.com or M.Nauck{at}diabeteszentrum.de.
Context: First-phase insulin secretion (within 10 min after sudden rise in plasma glucose) is reduced in type 2 diabetes mellitus (DM2). The incretin mimetic exenatide has glucoregulatory activities in DM2, including glucose-dependent enhancement of insulin secretion.
Objective: To determine whether exenatide can restore a more normal pattern of insulin secretion in subjects with DM2.
Design: Fasted subjects received intravenous (IV) insulin infusion to reach plasma glucose 4.4-5.6 mmol/L. Subjects received IV exenatide (DM2) or saline (DM2 and healthy volunteers), followed by IV glucose challenge.
Patients: Thirteen evaluable DM2 subjects: 11 male, 56 ± 7 y, BMI 31.7 ± 2.4 kg/m2, HbA1c 6.6 ± 0.7% (Mean ± SD) treated with diet/exercise (n = 1), metformin (n = 10) or acarbose (n = 2). Twelve healthy, weight-matched subjects with normal glucose tolerance: 9 male, 57 ± 9 y, BMI 32.0 ± 3.0 kg/m2.
Setting: Academic hospital
Main Outcome Measures: Plasma insulin, plasma C-peptide, insulin secretion rate derived by deconvolution, plasma glucagon
Results: DM2 subjects administered saline had diminished first-phase insulin secretion compared with healthy control subjects. Exenatide-treated DM2 subjects had an insulin secretory pattern similar to healthy subjects in both first (0-10 min) and second (10-180 min) phases after glucose challenge, in contrast to saline-treated DM2 subjects. In exenatide-treated DM2 subjects the most common adverse event was moderate nausea.
Conclusions: Short-term exposure to exenatide can restore the insulin secretory pattern in response to acute rises in glucose concentrations in DM2 patients who, in the absence of exenatide, do not display a first phase of insulin secretion. Loss of first-phase insulin secretion in DM2 patients may be restored by treatment with exenatide.
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