Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes.
The effects of different i.v. 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 x min) or placebo in the fasting state and after a solid test meal (containing [(13)C]octanoic acid). Blood was drawn for glucose, insulin, C-peptide, glucagon, and GLP-1 determinations. The gastric emptying rate was calculated from the (13)CO(2) 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 x 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.
Meier
Juris J
JJ
Department of Medicine I, St. Josef Hospital, Ruhr University, 44791 Bochum, Germany. Juris.Meier@ruhr-uni-bochum.de
Gallwitz
Baptist
B
Salmen
Stefan
S
Goetze
Oliver
O
Holst
Jens J
JJ
Schmidt
Wolfgang E
WE
Nauck
Michael A
MA
D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000097:blood; D005260:Female; D005746:Gastric Emptying; D005934:Glucagon / Q000008:administration & dosage*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000008:administration & dosage*; D019518:Postprandial Period; D011498:Protein Precursors / Q000008:administration & dosage*; D013997:Time Factors
D001786:Blood Glucose; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon