Similar Elimination Rates of Glucagon-Like peptide-1 in Obese Type 2 Diabetic Patients and Healthy Subjects

J Clin Endocrinol Metab. 2003 Jan;88(1):220-4. doi: 10.1210/jc.2002-021053.

Abstract

We have previously shown that type 2 diabetic patients have decreased plasma concentrations of glucagon-like peptide 1 (GLP-1) compared with healthy subjects after ingestion of a standard mixed meal. This decrease could be caused by differences in the metabolism of GLP-1. The objective of this study was to examine the pharmacokinetics of GLP-1 in healthy subjects and type 2 diabetic patients after iv bolus doses ranging from 2.5-25 nmol/subject. Bolus injections iv of 2.5, 5, 15, and 25 nmol of GLP-1 and a meal test were performed in six type 2 diabetic patients [age, mean (range): 56 (48-67) yr; body mass index: 31.2 (27.0-37.7) kg/m(2); fasting plasma glucose: 11.9 (8.3-14.3) mmol/liter; hemoglobin A(1C): 9.6 (7.0-12.5)%]. For comparison, six matched healthy subjects were examined. Peak plasma GLP-1 concentrations increased linearly with increasing doses of GLP-1 and were similar for type 2 diabetic patients and healthy subjects. The peak concentrations of total GLP-1 (C-terminal) after 2.5, 5, 15, and 25 nmol of GLP-1 were 357 +/- 56, 647 +/- 141, 1978 +/- 276, 3435 +/- 331 pmol/liter in the type 2 diabetic patients and 315 +/- 37, 676 +/- 64, 1848 +/- 146, 3168 +/- 358 pmol/liter, respectively, in the healthy subjects (not statistically significant). Peak concentrations of the intact GLP-1 peptide (N-terminal) were: 69 +/- 17, 156 +/- 44, 703 +/- 77, and 1070 +/- 117 pmol/liter in the type 2 diabetic patients and 75 +/- 14, 160 +/- 40, 664 +/- 79, 974 +/- 87 in the healthy subjects (not statistically significant). GLP-1 was eliminated rapidly with clearances of intact GLP-1 after 2.5, 5, 15, and 25 nmol of GLP-1 amounting to: 9.0 +/- 5.0, 8.1 +/- 6.0, 4.0 +/- 1.0, 4.0 +/- 1.0 liter/min in type 2 diabetic patients and 8.4 +/- 4.2, 7.6 +/- 4.5, 5.0 +/- 2.0, 5.0 +/- 1.0 liter/min in healthy subjects. The volume of distribution ranged from 9-26 liters per subject. No significant differences were found between healthy subjects and type 2 diabetic subjects. We conclude that elimination of GLP-1 is the same in obese type 2 diabetic patients and matched healthy subjects. The impaired incretin response seen after ingestion of a standard breakfast meal must therefore be caused by a decreased secretion of GLP-1 in type 2 diabetic patients.

MeSH terms

  • Aged
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus, Type 2 / blood*
  • Dose-Response Relationship, Drug
  • Female
  • Glucagon / administration & dosage
  • Glucagon / blood*
  • Glucagon / pharmacokinetics
  • Glucagon-Like Peptide 1
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Obesity*
  • Osmolar Concentration
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / blood*
  • Peptide Fragments / pharmacokinetics
  • Protein Precursors / administration & dosage
  • Protein Precursors / blood*
  • Protein Precursors / pharmacokinetics
  • Reference Values

Substances

  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon