Effects of metformin plus gliclazide compared with metformin alone on circulating endothelial progenitor cell in type 2 diabetic patients
- 462 Downloads
Circulating endothelial progenitor cells (EPCs) play an important role in the development and progression of diabetic vascular complications. The aim of this study was to investigate the effects of gliclazide plus metformin (GLIMET) compared with metformin alone (MET) on number and function of circulating EPCs in T2DM patients. Patients with newly diagnosed T2DM were randomly divided into two groups, receiving the following treatments for 16 weeks: MET group (assuming metformin 500–2500 mg/day, n = 24) and GLIMET group [assuming gliclazide (modified release, 30–60 mg/day) + metformin (250–1000 mg/day), n = 23]. Circulating EPCs were quantified by flow cytometry, and the ability to uptake LDL and stain for lectin were used as another method of characterizing EPCs ex vivo. The functions of circulating EPCs were evaluated by colony-forming units (CFU) and migration. The status of oxidative stress was analyzed by serum-free malonaldehyde (MDA) and superoxide dismutase (SOD). There were no significant differences in clinical characteristics and number and function of circulating EPCs between two groups at baseline. Glycemic responses were similar after treatments. Compared with MET group, GLIMET group was associated with an increase in circulating EPCs number, DiLDL–lectin-positive EPCs, and migration. The mean improvements in MDA and SOD of GLIMET group were more strongly upregulated than those of MET group. This study demonstrated that both metformin mono-treatment and metformin plus gliclazide combination treatment provided with improvements in number and function of circulating EPCs. Compared with metformin mono-treatment, early use of combination therapy with gliclazide plus metformin made more effective improvements in circulating EPCs.
KeywordsEndothelial progenitor cell Type 2 diabetes Metformin Gliclazide Oxidative stress
This study was supported by grants from scientific and technological project of Hubei province (No. 2007AA302B04) and the scientific research foundation from health department of Hubei province (No. JX3A04).
The authors declare that there is no conflict of interest that would prejudice its impartiality.
- 3.G.P. Fadini, M. Miorin, M. Facco, S. Bonamico, I. Baesso, F. Grego, M. Menegolo, S.V. de Kreutzenberg, A. Tiengo, C. Agostini, A. Avogaro, Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J. Am. Coll. Cardiol. 45, 1449–1457 (2005)CrossRefPubMedGoogle Scholar
- 4.O.M. Tepper, R.D. Galiano, J.M. Capla, C. Kalka, P.J. Gagne, G.R. Jacobowitz, J.P. Levine, G.C. Gurtner, Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106, 2781–2786 (2002)CrossRefPubMedGoogle Scholar
- 5.G.P. Fadini, S. Sartore, M. Albiero, I. Baesso, E. Murphy, M. Menegolo, F. Grego, S. Vigili de Kreutzenberg, A. Tiengo, C. Agostini, A. Avogaro, Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler. Thromb. Vasc. Biol. 26, 2140–2146 (2006)CrossRefPubMedGoogle Scholar
- 9.ADVANCE Collaborative Group, A. Patel, S. MacMahon, J. Chalmers, B. Neal, L. Billot, M. Woodward, M. Marre, M. Cooper, P. Glasziou, D. Grobbee, P. Hamet, S. Harrap, S. Heller, L. Liu, G. Mancia, C.E. Mogensen, C. Pan, N. Poulter, A. Rodgers, B. Williams, S. Bompoint, B.E. de Galan, R. Joshi, F. Travert, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 358, 2560–2572 (2008)CrossRefPubMedGoogle Scholar
- 13.G. Formoso, E.A. De Filippis, N. Michetti, P. Di Fulvio, A. Pandolfi, T. Bucciarelli, G. Ciabattoni, A. Nicolucci, G. Davì, A. Consoli, Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects. Diabetes Metab. Res. Rev. 24, 231–237 (2008)CrossRefPubMedGoogle Scholar
- 15.The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20, 1183–1197 (1997)Google Scholar
- 18.Y. Numaguchi, T. Sone, K. Okumura, M. Ishii, Y. Morita, R. Kubota, K. Yokouchi, H. Imai, M. Harada, H. Osanai, T. Kondo, T. Murohara, The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction. Circulation 114, I114–I119 (2006)CrossRefPubMedGoogle Scholar
- 19.C. Murphy, G.S. Kanaganayagam, B. Jiang, P.J. Chowienczyk, R. Zbinden, M. Saha, S. Rahman, A.M. Shah, M.S. Marber, M.T. Kearney, Vascular dysfunction and reduced circulating endothelial progenitor cells in young healthy UK south Asian men. Arterioscler. Thromb. Vasc. Biol. 27, 936–942 (2007)CrossRefPubMedGoogle Scholar
- 27.C. Werner, C.H. Kamani, C. Gensch, M. Böhm, U. Laufs, The peroxisome proliferator-activated receptor-gamma agonist pioglitazone increases number and function of endothelial progenitor cells in patients with coronary artery disease and normal glucose tolerance. Diabetes 56, 2609–2615 (2007)CrossRefPubMedGoogle Scholar
- 33.N. Musi, M.F. Hirshman, J. Nygren, M. Svanfeldt, P. Bavenholm, O. Rooyackers, G. Zhou, J.M. Williamson, O. Ljunqvist, S. Efendic, D.E. Moller, A. Thorell, L.J. Goodyear, Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51, 2074–2081 (2002)CrossRefPubMedGoogle Scholar
- 35.K. Ukinc, S. Eminagaoglu, H.O. Ersoz, C. Erem, C. Karahan, A.B. Hacihasanoglu, M. Kocak, A novel indicator of widespread endothelial damage and ischemia in diabetic patients: ischemia-modified albumin. Endocrine 26, (2009) [Epub ahead of print]Google Scholar