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

Date

2012

Authors

Ma, J.
Pilichiewicz, A.
Feinle-Bisset, C.
Wishart, J.
Jones, K.
Horowitz, M.
Rayner, C.

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Diabetic Medicine, 2012; 29(5):604-608

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J. Ma, A. N. Pilichiewicz, C. Feinle-Bisset, J. M. Wishart, K. L. Jones, M. Horowitz and C. K. Rayner

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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.

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© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK

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