title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. pmvc@dadlnet.dk
authors.forename: P V
authors.initials: PV
authors.lastname: Højberg
authors.forename: T
authors.initials: T
authors.lastname: Vilsbøll
authors.forename: M
authors.initials: M
authors.lastname: Zander
authors.forename: F K
authors.initials: FK
authors.lastname: Knop
authors.forename: T
authors.initials: T
authors.lastname: Krarup
authors.forename: A
authors.initials: A
authors.lastname: Vølund
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: S
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon