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Diabeteszentrum Bad Lauterberg (F.F., M.A.N.), D-37431 Bad Lauterberg im Harz, Germany; Eli Lilly & Co. (M.T.), Hamburg, Germany, and Indianapolis, Indiana 46285; Department of Medical Physiology (J.J.H.), Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark; and Amylin Pharmaceuticals (A.E.H., N.N., L.L.N., M.S.F., D.D.K.), San Diego, California 92121
Address all correspondence and requests for reprints to: Professor Dr. Med. Michael Nauck, Diabeteszentrum Bad Lauterberg, Kirchberg 21, D-37431 Bad Lauterberg im Harz, Germany. E-mail: m.nauck{at}diabeteszentrum.de.
Context: First-phase insulin secretion (within 10 min after a 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: The objective of the study was to determine whether exenatide can restore a more normal pattern of insulin secretion in subjects with DM2.
Design: Fasted subjects received iv insulin infusion to reach plasma glucose 4.4–5.6 mmol/liter. Subjects received iv exenatide (DM2) or saline (DM2 and healthy volunteers), followed by iv glucose challenge.
Patients: Thirteen evaluable DM2 subjects were included in the study: 11 males, two females; age, 56 ± 7 yr; body mass index, 31.7 ± 2.4 kg/m2; hemoglobin A1c, 6.6 ± 0.7% (mean ± SD) treated with diet/exercise (n = 1), metformin (n = 10), or acarbose (n = 2). Controls included 12 healthy, weight-matched subjects with normal glucose tolerance: nine males, three females; age, 57 ± 9 yr; and body mass index, 32.0 ± 3.0 kg/m2.
Setting: The study was conducted at an academic hospital.
Main Outcome Measures: Plasma insulin, plasma C-peptide, insulin secretion rate (derived by deconvolution), and plasma glucagon were the main outcome measures.
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 (two of 13 subjects).
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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