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Diabetologia. 2008 Apr;51(4):632-40. doi: 10.1007/s00125-008-0943-x. Epub 2008 Feb 22.

Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes.

Author information

1
Department of Endocrinology, Hvidovre Hospital, Kettegaards Allé 30, 2650 Hvidovre, Denmark. pmvc@dadlnet.dk

Abstract

AIMS/HYPOTHESIS:

The ability of glucagon-like peptide-1 (GLP-1) to enhance beta cell responsiveness to i.v. glucose is impaired in patients with type 2 diabetes mellitus compared with healthy individuals. We investigated whether 4 weeks of near normalisation of blood glucose (BG) improves the potentiation of glucose-stimulated insulin secretion by GLP-1.

METHODS:

Nine obese patients with type 2 diabetes and inadequate glycaemic control (HbA(1c) 8.0+/-0.4%) were investigated before and after 4 weeks of near normalisation of BG using insulin treatment (mean diurnal blood glucose 6.4+/-0.3 mmol/l, HbA(1c) 6.6+/-0.3%). Nine matched healthy participants were also studied. Beta cell function was investigated before and after insulin treatment using stepwise glucose infusions and infusion of saline or GLP-1 (1.0 pmol kg(-1) min(-1)), resulting in supraphysiological total GLP-1 concentrations of approximately 200 pmol/l. The responsiveness to glucose or glucose+GLP-1 was expressed as the slope of the linear regression line relating insulin secretion rate (ISR) and plasma glucose concentration (pmol kg(-1) min(-1) [mmol/l](-1)).

RESULTS:

In the diabetic participants, the slopes during glucose+saline infusion did not differ before and after insulin treatment (0.33+/-0.07 and 0.39+/-0.04, respectively; p=NS). In contrast, near normalisation of blood glucose improved beta cell sensitivity to glucose during glucose+GLP-1 infusion (1.27+/-0.2 before vs 1.73+/-0.31 after; p<0.01). In the healthy participants, the slopes during the glucose+saline and glucose+GLP-1 infusions were 1.01+/-0.14 and 4.79+/-0.53, respectively.

CONCLUSIONS/INTERPRETATION:

A supraphysiological dose of GLP-1 enhances beta cell responses to glucose in patients with type 2 diabetes, and 4 weeks of near normalisation of blood glucose further improves this effect.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00612625.

PMID:
18292985
DOI:
10.1007/s00125-008-0943-x
[Indexed for MEDLINE]

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