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BioMed Research International
Volume 2013, Article ID 256043, 15 pages
Review Article

Glucose Toxic Effects on Granulation Tissue Productive Cells: The Diabetics’ Impaired Healing

1Tissue Repair and Cytoprotection Research Group, Center for Genetic Engineering and Biotechnology, Playa, CP 10600 Havana, Cuba
2Institute for Wound Research, University of Florida, Gainesville, FL, USA
3Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Playa, CP 10600 Havana, Cuba
4General Direction, Center for Genetic Engineering and Biotechnology, Playa, CP 10600 Havana, Cuba

Received 18 August 2012; Accepted 24 November 2012

Academic Editor: David G. Armstrong

Copyright © 2013 Jorge Berlanga-Acosta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Type 2 diabetes mellitus is a metabolic noncommunicable disease with an expanding pandemic magnitude. Diabetes predisposes to lower extremities ulceration and impairs the healing process leading to wound chronification. Diabetes also dismantles innate immunity favoring wound infection. Amputation is therefore acknowledged as one of the disease’s complications. Hyperglycemia is the proximal detonator of systemic and local toxic effectors including proinflammation, acute-phase proteins elevation, and spillover of reactive oxygen and nitrogen species. Insulin axis deficiency weakens wounds’ anabolism and predisposes to inflammation. The systemic accumulation of advanced glycation end-products irreversibly impairs the entire physiology from cells-to-organs. These factors in concert hamper fibroblasts and endothelial cells proliferation, migration, homing, secretion, and organization of a productive granulation tissue. Diabetic wound bed may turn chronically inflammed, procatabolic, and an additional source of circulating pro-inflammatory cytokines, establishing a self-perpetuating loop. Diabetic fibroblasts and endothelial cells may bear mitochondrial damages becoming prone to apoptosis, which impairs granulation tissue cellularity and perfusion. Endothelial progenitor cells recruitment and tubulogenesis are also impaired. Failure of wound reepithelialization remains a clinical challenge while it appears to be biologically multifactorial. Ulcer prevention by primary care surveillance, education, and attention programs is of outmost importance to reduce worldwide amputation figures.