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Comments to Bagger et al: Impaired regulation of the incretin effect in patients with type 2 diabetes.


J Clin Endocrinol Metab 96:737-745 (2011)

The incretin effect is defined as the augmented insulin secretion after oral versus intrave-nous glucose administration and is due to the release from the gut of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) after oral glucose; these incretin hormones augment glucose-stimulated insulin secretion (1). The incretin function is of key importance for normal glucose levels after oral glucose. It has also been shown that the incretin effect is impaired in type 2 diabetes (2). This is mainly due to impaired action on insulin secretion by the incretin hormone GIP in type 2 diabetes (3) and a reduced incretin hormone secretion may also contribute in some patients (4).

The new study by Dr Bagger and co-authors presents novel information on the regulation of the incretin function under normal conditions and in type 2 diabetes (5). They challenged healthy volunteers and patients with type 2 diabetes with 25g, 50g and 125g oral glucose. They found in healthy subjects that the incretin effect (defined as the difference in insulin response after oral vs intravenous glucose) was increased by increased glucose and that the increase was such that in spite of the larger glucose challenge at 125g, the glucose peak was not higher due to augmented insulin secretion. They also showed that this increased incretin function was impaired in type 2 diabetes. Thus, these patients with diabetes had impaired increase in incretin function after increasing glucose load, resulting in hyperglycemia. The authors also showed that GIP and GLP-1 secretion was increased by the higher glucose load to the same extent as in healthy subjects and therefore, the main conclusion was that patients with type 2 diabetes had defective islet effects of the incretin hormones.

The study therefore presents new data on incretin physiology and pathophysiology and in particular shows that defective islet response to incretin hormones may explain the hyperglycemia following increased glucose load.

Bo Ahrén – Sweden

1) Holst JJ, Vilsbøll T, Deacon CF 2009 The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 297:127-136
2) Nauck M, Stockmann F, Ebert R, Creutzfeldt W 1986 Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46-52
3) Nauck MA, Heimesaat MM, Ørskov C, Holst JJ, Ebert R, Creutzfeldt W 1993 Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type 2 diabetes mellitus. J Clin Invest 91:301-307.
4) Nauck MA, Vardarli I, Deacon CF, Holst JJ, Meier JJ 2011 Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down? Diabetologia 54:10-18.
5) Bagger JI, Knop FK, Lund A, Vestergaard H, Holst JJ, Vilsbøll T 2011 Im-paired regulation of the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab 96:737-745