Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes

Diabetologia. 2009 Feb;52(2):199-207. doi: 10.1007/s00125-008-1195-5. Epub 2008 Nov 27.

Abstract

Objective: The incretin effect is attenuated in patients with type 2 diabetes mellitus, partly as a result of impaired beta cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The aim of the present study was to investigate whether 4 weeks of near-normalisation of the blood glucose level could improve insulin responses to GIP and GLP-1 in patients with type 2 diabetes.

Methods: Eight obese patients with type 2 diabetes with poor glycaemic control (HbA(1c) 8.6 +/- 1.3%), were investigated before and after 4 weeks of near-normalisation of blood glucose (mean blood glucose 7.4 +/- 1.2 mmol/l) using insulin treatment. Before and after insulin treatment the participants underwent three hyperglycaemic clamps (15 mmol/l) with infusion of GLP-1, GIP or saline. Insulin responses were evaluated as the incremental area under the plasma C-peptide curve.

Results: Before and after near-normalisation of blood glucose, the C-peptide responses did not differ during the early phase of insulin secretion (0-10 min). The late phase C-peptide response (10-120 min) increased during GIP infusion from 33.0 +/- 8.5 to 103.9 +/- 24.2 (nmol/l) x (110 min)(-1) (p < 0.05) and during GLP-1 infusion from 48.7 +/- 11.8 to 126.6 +/- 32.5 (nmol/l) x (110 min)(-1) (p < 0.05), whereas during saline infusion the late-phase response did not differ before vs after near-normalisation of blood glucose (40.2 +/- 11.2 vs 46.5 +/- 12.7 [nmol/l] x [110 min](-1)).

Conclusions: Near-normalisation of blood glucose for 4 weeks improves beta cell responsiveness to both GLP-1 and GIP by a factor of three to four. No effect was found on beta cell responsiveness to glucose alone. CLINICALTRIALS.GOV ID NO.: NCT 00612950.

Funding: This study was supported by The Novo Nordisk Foundation, The Medical Science Research Foundation for Copenhagen.

Trial registration: ClinicalTrials.gov NCT00612950.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Fasting
  • Fructosamine / blood
  • Gastric Inhibitory Polypeptide / administration & dosage
  • Gastric Inhibitory Polypeptide / pharmacology*
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Infusions, Intravenous
  • Insulin / blood
  • Male
  • Middle Aged
  • Reference Values

Substances

  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Insulin
  • Fructosamine
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1

Associated data

  • ClinicalTrials.gov/NCT00612950