Effects of variations in duodenal glucose load on glycaemic, insulin, and incretin responses in type 2 diabetes

Diabet Med. 2012 May;29(5):604-8. doi: 10.1111/j.1464-5491.2011.03496.x.

Abstract

Aims: Postprandial glucagon-like peptide-1 (GLP-1) secretion and the 'incretin effect' have been reported to be deficient in Type 2 diabetes, but most studies have not controlled for variations in the rate of gastric emptying. We evaluated blood glucose, and plasma insulin, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) responses to intraduodenal glucose in Type 2 diabetes, and compared these with data from healthy controls.

Methods: Eight males with well-controlled Type 2 diabetes, managed by diet alone, were studied on four occasions in single-blind, randomized order. Blood glucose, and plasma insulin, GLP-1, and GIP were measured during 120-min intraduodenal glucose infusions at 1 kcal/min (G1), 2 kcal/min (G2) and 4 kcal/min (G4) or saline control.

Results: Type 2 patients had higher basal (P < 0.0005) and incremental (P < 0.0005) blood glucose responses to G2 and G4, when compared with healthy controls. In both groups, the stimulation of insulin and GLP-1 by increasing glucose loads was not linear; responses to G1 and G2 were minimal, whereas responses to G4 were much greater (P < 0.005 for each) (incremental area under the GLP-1 curve 224 ± 65, 756 ± 331 and 2807 ± 473 pmol/l.min, respectively, in Type 2 patients and 373 ± 231, 505 ± 161 and 1742 ± 456 pmol/l.min, respectively, in healthy controls). The GLP-1 responses appeared comparable in the two groups. In both groups there was a load-dependent increase in plasma GIP with no difference between them.

Conclusions: In patients with well-controlled Type 2 diabetes, blood glucose, insulin and GLP-1 responses are critically dependent on the small intestinal glucose load, and GLP-1 responses are not deficient.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Duodenum / metabolism*
  • Duodenum / physiopathology
  • Gastric Emptying
  • Gastric Inhibitory Polypeptide / blood*
  • Gastric Inhibitory Polypeptide / metabolism
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucose / administration & dosage*
  • Glucose / metabolism*
  • Humans
  • Incretins / blood*
  • Incretins / metabolism
  • Insulin / blood*
  • Insulin / metabolism
  • Insulin Secretion
  • Male
  • Middle Aged
  • Postprandial Period
  • Single-Blind Method

Substances

  • Blood Glucose
  • Incretins
  • Insulin
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucose