Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes.
OBJECTIVE
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
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.
Højberg
P V
PV
Department of Endocrinology, Hvidovre Hospital, Kettegaards Allé 30, 2650 Hvidovre, Denmark. pmvc@dadlnet.dk
Zander
M
M
Vilsbøll
T
T
Knop
F K
FK
Krarup
T
T
Vølund
A
A
Holst
J J
JJ
Madsbad
S
S
D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1; D005947:Glucose