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

TY - JOUR

T1 - Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes

AU - Højberg, P V

AU - Zander, M

AU - Vilsbøll, T

AU - Knop, F K

AU - Krarup, T

AU - Vølund, A

AU - Holst, Jens Juul

AU - Madsbad, S

PY - 2008/4

Y1 - 2008/4

N2 - 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.

AB - 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.

KW - Blood Glucose

KW - Body Mass Index

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Glucagon-Like Peptide 1

KW - Glucose

KW - Humans

KW - Insulin

KW - Kinetics

KW - Male

KW - Middle Aged

KW - Peptide Fragments

KW - Reference Values

U2 - 10.1007/s00125-008-0943-x

DO - 10.1007/s00125-008-0943-x

M3 - Journal article

C2 - 18292985

SN - 0012-186X

VL - 51

SP - 632

EP - 640

JO - Diabetologia

JF - Diabetologia

IS - 4

ER -