Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Feb;52(2):199-207.
doi: 10.1007/s00125-008-1195-5. Epub 2008 Nov 27.

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

P V Højberg  1 , T Vilsbøll, R Rabøl, F K Knop, M Bache, T Krarup, J J Holst, S Madsbad
Affiliations

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

P V Højberg et al. Diabetologia. 2009 Feb.

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.

PubMed Disclaimer

References

    1. Ann Intern Med. 1996 Jan 1;124(1 Pt 2):136-45 - PubMed
    1. J Clin Endocrinol Metab. 2001 Aug;86(8):3717-23 - PubMed
    1. N Engl J Med. 1992 May 14;326(20):1316-22 - PubMed
    1. Br Med J. 1976 May 22;1(6020):1252-4 - PubMed
    1. Diabetes Metab Rev. 1992 Jul;8(2):149-77 - PubMed

Publication types

MeSH terms

Associated data