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Rosiglitazone improves endothelial function and inflammation but not asymmetric dimethylarginine or oxidative stress in patients with type 2 diabetes mellitus

Department of Research, St Paul Heart Clinic, St Paul, MN, USA, School of Medicine, University of Minnesota, Minneapolis, MN, USA, kelly105{at}umn.edu

Andrea M. Thelen

Department of Research, St Paul Heart Clinic, St Paul, MN, USA

Daniel R. Kaiser

School of Medicine, University of Minnesota, Minneapolis, MN, USA

J. Michael Gonzalez-Campoy

Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, MN, USA

Alan J. Bank

Department of Research, St Paul Heart Clinic, St Paul, MN, USA, School of Medicine, University of Minnesota, Minneapolis, MN, USA

We compared the vascular effects of rosiglitazone versus glyburide and evaluated asymmetric dimethylarginine (ADMA) and oxidative stress as potential mechanisms associated with changes in vascular health in patients with type 2 diabetes mellitus (T2DM). Patients were randomized to 6 months of either rosiglitazone (n = 20) or glyburide (n = 16) in addition to metformin. The following variables were measured pre- and post-treatment: glucose, insulin, homeostasis model assessment (HOMA), hemoglobin A1c (HbA1c), C-peptide, blood pressure, lipids, C-reactive protein (CRP), ADMA, 8-isoprostane, oxidized LDL cholesterol, brachial artery flow-mediated dilation (FMD), endothelium-independent dilation (EID), and brachial and carotid artery stiffness. Rosiglitazone and glyburide treatment resulted in significant and equivalent decreases in glucose (p < 0.0001) and HbA1c (p < 0.0001), with a trend toward decreased HOMA (p = 0.09). Rosiglitazone significantly decreased C-peptide (p < 0.01) with a strong trend toward decreased fasting insulin (p = 0.05). Rosiglitazone reduced CRP compared with glyburide (p = 0.001), but no differences were observed between groups for ADMA or the markers of oxidative stress. Rosiglitazone significantly improved FMD (p < 0.05) with trends toward improvements in carotid artery distension (p = 0.099) and distensibility (p = 0.078). In conclusion, compared with glyburide, rosiglitazone improves endothelial function and CRP in patients with T2DM. These improvements are not associated with reductions in ADMA or markers of oxidative stress.

Key Words: asymmetric dimethylarginine • endothelial function • oxidative stress • rosiglitazone • type 2 diabetes mellitus

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