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

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.