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. et al. (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. (doi: 10.1016/j.diabres.2011.07.014)

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Publisher's URL: http://dx.doi.org/10.1016/j.diabres.2011.07.014

Abstract

<p><b>Aim:</b> 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.</p> <p><b>Methods:</b> 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).</p> <p><b>Results:</b> 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.</p> <p><b>Conclusion:</b> 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.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rumley, Dr Ann and Lowe, Professor Gordon
Authors: Stephens, J.W., Bodvarsdottir, T.B., Wareham, K., Prior, S.L., Bracken, R.M., Lowe, G.D., Rumley, A., Dunseath, G., Luzio, S., Deacon, C.F., Holst, J.J., and Bain, S.C.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Diabetes Research and Clinical Practice
ISSN:0168-8227
ISSN (Online):1872-8227

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