TY - JOUR

T1 - Four weeks of near-normalization of blood glucose has no effect on postprandial GLP-1 and GIP secretion, but augments pancreatic B-cell responsiveness to a meal in patients with Type 2 diabetes

AU - Højberg, P V

AU - Vilsbøll, T

AU - Zander, M

AU - Knop, F K

AU - Krarup, T

AU - Vølund, A

AU - Holst, Jens Juul

AU - Madsbad, S

PY - 2008/11

Y1 - 2008/11

N2 - OBJECTIVE: The aim of the present study was to investigate whether 4 weeks of near-normalization of blood glucose (BG) improves incretin hormone secretion and pancreatic B-cell function during a mixed meal.RESEARCH DESIGN AND METHODS: Nine patients with Type 2 diabetes in poor glycaemic control [glycated haemoglobin (HbA(1c)) 8.0 +/- 0.4%] were investigated before and after 4 weeks of near-normalization of BG (mean BG 6.4 +/- 0.3 mmol/l) using insulin treatment. HbA(1c) after insulin treatment was 6.6 +/- 0.3%. For comparison, nine healthy control subjects were also studied. Postprandial glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) incremental responses were assessed during a mixed meal test. Fasting and postprandial pancreatic B-cell function was determined from calculations of insulin secretion rates in relation to plasma glucose.RESULTS: There was no difference in IAUC(totalGLP-1) or in IAUC(totalGIP) between the two experimental days. B-cell sensitivity to glucose (insulinogenic index) did not differ before and after insulin treatment in the fasting state (0.21 +/- 0.17 vs. 0.25 +/- 0.10 pmol kg(-1) min(-1)/mmol l(-1)), but improved significantly during the first 30 min after start of the meal (0.28 +/- 0.07 vs. 0.46 +/- 0.06 pmol kg(-1) min(-1)/mmol l(-1)) and during the following 4 h (0.34 +/- 0.09 vs. 0.56 +/- 0.07 pmol kg(-1) min(-1)/ mmol l(-1)). The B-cell responsiveness to changes in plasma glucose, expressed as the slope of the linear relationship between the insulin secretion rate and the concomitant plasma glucose increased from 0.59 +/- 0.16 to 0.94 +/- 0.13 pmol kg(-1) min(-1)/ mmol l(-1) (P < 0.07).CONCLUSIONS: Four weeks of near-normalization of BG had no effect on postprandial secretion of incretin hormones. Nevertheless, several parameters of meal-induced insulin secretion improved after insulin treatment.

AB - OBJECTIVE: The aim of the present study was to investigate whether 4 weeks of near-normalization of blood glucose (BG) improves incretin hormone secretion and pancreatic B-cell function during a mixed meal.RESEARCH DESIGN AND METHODS: Nine patients with Type 2 diabetes in poor glycaemic control [glycated haemoglobin (HbA(1c)) 8.0 +/- 0.4%] were investigated before and after 4 weeks of near-normalization of BG (mean BG 6.4 +/- 0.3 mmol/l) using insulin treatment. HbA(1c) after insulin treatment was 6.6 +/- 0.3%. For comparison, nine healthy control subjects were also studied. Postprandial glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) incremental responses were assessed during a mixed meal test. Fasting and postprandial pancreatic B-cell function was determined from calculations of insulin secretion rates in relation to plasma glucose.RESULTS: There was no difference in IAUC(totalGLP-1) or in IAUC(totalGIP) between the two experimental days. B-cell sensitivity to glucose (insulinogenic index) did not differ before and after insulin treatment in the fasting state (0.21 +/- 0.17 vs. 0.25 +/- 0.10 pmol kg(-1) min(-1)/mmol l(-1)), but improved significantly during the first 30 min after start of the meal (0.28 +/- 0.07 vs. 0.46 +/- 0.06 pmol kg(-1) min(-1)/mmol l(-1)) and during the following 4 h (0.34 +/- 0.09 vs. 0.56 +/- 0.07 pmol kg(-1) min(-1)/ mmol l(-1)). The B-cell responsiveness to changes in plasma glucose, expressed as the slope of the linear relationship between the insulin secretion rate and the concomitant plasma glucose increased from 0.59 +/- 0.16 to 0.94 +/- 0.13 pmol kg(-1) min(-1)/ mmol l(-1) (P < 0.07).CONCLUSIONS: Four weeks of near-normalization of BG had no effect on postprandial secretion of incretin hormones. Nevertheless, several parameters of meal-induced insulin secretion improved after insulin treatment.

KW - Area Under Curve

KW - Blood Glucose

KW - Diabetes Mellitus, Type 2

KW - Eating

KW - Fasting

KW - Female

KW - Gastric Inhibitory Polypeptide

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Humans

KW - Hyperglycemia

KW - Insulin

KW - Insulin-Secreting Cells

KW - Male

KW - Middle Aged

KW - Postprandial Period

U2 - 10.1111/j.1464-5491.2008.02579.x

DO - 10.1111/j.1464-5491.2008.02579.x

M3 - Journal article

C2 - 19046215

VL - 25

SP - 1268

EP - 1275

JO - Diabetic Medicine Online

JF - Diabetic Medicine Online

SN - 1464-5491

IS - 11

ER -