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Normalization of Glucose Concentrations and Deceleration of Gastric Emptying after Solid Meals during Intravenous Glucagon-Like Peptide 1 in Patients with Type 2 Diabetes

Department of Medicine I, St. Josef Hospital, Ruhr University (J.J.M., B.G., S.S., O.G., W.E.S., M.A.N.), 44791 Bochum, Germany; Department of Medical Physiology, The Panum Institute, University of Copenhagen (J.J.H.), 2200 Copenhagen, Denmark; and Diabeteszentrum (M.A.N.), 37431 Bad Lauterberg, Germany

Address all correspondence and requests for reprints to: Dr. Juris J. Meier, Medizinische Klinik I, St. Josef Hospital, Klinikum der Ruhr Universität Bochum, Gudrunstrasse 56, 44791 Bochum, Germany. E-mail: Juris.Meier{at}ruhr-uni-bochum.de.

The effects of different iv doses of glucagon-like peptide 1 (GLP-1) on glucose homeostasis and gastric emptying were compared in patients with type 2 diabetes. Twelve patients with type 2 diabetes received three different infusion rates of GLP-1 (0.4, 0.8, and 1.2 pmol/kg·min) or placebo in the fasting state and after a solid test meal (containing [¹³C]octanoic acid). Blood was drawn for glucose, insulin, C-peptide, glucagon, and GLP-1 determinations. The gastric emptying rate was calculated from the ¹³CO₂ excretion rates in breath samples. Statistics were determined using repeated measures ANOVA and Duncan’s post hoc test.

Plasma glucose concentrations were equally normalized with all GLP-1 doses (P < 0.001). Insulin and C-peptide concentrations dose-dependently rose during GLP-1 infusion in the fasting state (P < 0.05), but were dose-dependently reduced by GLP-1 after meal ingestion (P = 0.0031 and 0.0074, respectively). Glucagon secretion was suppressed with GLP-1. Gastric emptying was decelerated by GLP-1 in a dose-dependent fashion (P < 0.001).

Despite a dose-dependent stimulation of insulin secretion, glucose normalization can be achieved even with 0.4 pmol GLP-1/kg·min. Due to the dose-dependent inhibition of gastric emptying, lower GLP-1 doses than previously used may be as suitable for glucose control in patients with type 2 diabetes.

This work was supported by Deutsche Forschungsgemeinschaft (Na 203/6-1) and FoRUM (F348/2002).

Abbreviations: GLP-1, Glucagon-like peptide 1; PDR, percentage dose of ¹³C recovered.

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