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Effects of short-term therapy with glibenclamide and repaglinide on incretin hormones and oxidative damage associated with postprandial hyperglycaemia in people with type 2 diabetes mellitus

Stephens, J. W., Bodvarsdottir, T. B., Wareham, K., Prior, S. L., Bracken, R. M., Lowe, G. D., Rumley, A., Dunseath, Gareth John, Luzio, Stephen Denis, Deacon, C. F., Holst, J. J. and Bain, S. 2011. Effects of short-term therapy with glibenclamide and repaglinide on incretin hormones and oxidative damage associated with postprandial hyperglycaemia in people with type 2 diabetes mellitus. Diabetes Research and Clinical Practice 94 (2) , pp. 199-206. 10.1016/j.diabres.2011.07.014

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Abstract

Aim To examine the effects of glibenclamide and repaglinide on glucose stimulated insulin release, incretins, oxidative stress and cell adhesion molecules in patients with type 2 diabetes suboptimally treated with metformin. Methods A randomized clinical trial was performed recruiting 27 subjects (HbA1c between 7.5 and 10.5%) free from cardiovascular and renal disease. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), total antioxidant status, F2-isoprostane, interleukin-6 and cell adhesion molecules were measured during an oral glucose load at baseline and after eight weeks of treatment. The areas under the curve were analysed at 45, 60 and 120 min (AUC45, AUC60, AUC120). Results Significant improvements in glucose were observed with repaglinide (HBA1c: −1.5%, fasting glucose: −2.8 mmol/L, 2-h glucose: −3.7 mmol/L, AUC120: −18.9%) and glibenclamide (−1.0%, −2.2 mmol/L, −2.5 mmol/L, −17.5%). Repaglinide was also associated with an increase in the AUC60 and AUC120 for insulin (+56%, +61%) and C-peptide (+41%, +36%). GLP-1, GIP, IL-6, ICAM-1 and E-selectin levels did not change in either group. No association was observed between GLP-1, GIP-1 and plasma markers of oxidative stress. Conclusion Repaglinide is associated with improved postprandial glycaemic control via insulin and C-peptide release. We observed no direct effects of glibenclamide or repaglinide on plasma levels of GLP-1 or GIP. We observed no associations of GLP-1 and GIP with plasma markers of oxidative stress.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: glibenclamide, repaglinide, GLP-1, GIP, insulin, oxidative stress, diabetes
Publisher: Elsevier
ISSN: 0168-8227
Last Modified: 04 Jun 2017 03:39
URI: http://orca.cf.ac.uk/id/eprint/24518

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