Endothelial Progenitor Cells and the Diabetic Paradox

  1. Gian Paolo Fadini, MD1,
  2. Saverio Sartore, PHD2,
  3. Ilenia Baesso, PHD3,
  4. Maddalena Lenzi, BSC2,
  5. Carlo Agostini, MD3,
  6. Antonio Tiengo, MD1 and
  7. Angelo Avogaro, MD, PHD1
  1. 1Department of Clinical and Experimental Medicine, Metabolic Division, University of Padua, Medical School, Padua, Italy
  2. 2Department of Experimental Biomedical Sciences, University of Padua, Medical School, Padua, Italy
  3. 3Department of Clinical and Experimental Medicine, Clinical Immunology, University of Padua, Medical School, Padua, Italy
  1. Address correspondence reprint requests to Gian Paolo Fadini, MD, Dipartimento di Medicina Clinica e Sperimentale, Divisione di Malattie del Metabolismo, Policlinico Universitario, v. Giustiniani, 2, 35100 Padova, Italy. E-mail: gianpaolofadini{at}hotmail.com

An unexplained paradox puzzles diabetologists: diabetic patients must face both poor vessel growth in ischemic heart and limbs and increased angiogenesis in retinal complications (1,2).

Endothelial progenitor cells (EPCs) are marrow-derived cells involved in adult neovascularization and endothelial homeostasis (3,4). It has been postulated that low EPCs in peripheral blood may have a role in cardiovascular disease, and we have demonstrated that EPCs are reduced in macrovascular diabetes complications (5,6). On the other hand, an excess of EPCs may be involved in pathologic neoangiogenesis of cancer and proliferative retinopathy (7,8). Therefore, diabetes complications may be associated with both decreased and increased EPCs. Recently, novel therapeutic approaches have been directed to enrich the EPC pool in ischemic diseases and to block EPC function in proliferative diseases (9,10). These approaches in diabetic subjects require cautious evaluation of the implications carried by the paradox and new studies to unravel its causes (11,12). This study was carried out to investigate the contemporaneous effects of retinal and peripheral vascular complications on circulating progenitor cells.

RESEARCH DESIGN AND METHODS

Ethics committee approval was obtained, and after giving informed consent, 60 type 2 diabetic patients were prospectively included. Patients were characterized in terms of peripheral arterial disease (PAD) and diabetic retinopathy (DR) as the most representative complications at the two extremities of the diabetic paradox. PAD was diagnosed by minimal criteria (including history of claudication or rest pain, pulse examination, ankle-brachial indexes, and ultrasonography) and eventually confirmed by angiography. Diabetic retinopathy (severe nonproliferative or proliferative) was defined by a dilated and comprehensive eye examination and acquisition of high-quality stereoscopic photographs by …

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