Impacto perjudicial del exceso agudo y crónico de glucosa en células involucradas en la cicatrización: fibroblastos, miofibroblastos y células precursoras vasculares

Type 2 diabetes mellitus comprises a group of non-communicable metabolic diseases with an expanding pandemic magnitude. Diabetes predisposes to lower extremities ulceration and impairs the healing process leading to wounds chronifi cation. Diabetes also dismantles innate immunity favoring wound infection. Amputation is therefore acknowledged as one of the disease’s complications. Hyperglycemia appears as the proximal detonator of toxic effectors including pro-infl ammation, spillover of reactive oxygen and nitrogen species. The systemic accumulation of advanced glycation end-products irreversibly impairs the entire physiology from cells-to-organs. Insulin axis defi ciency weakens wounds’ anabolism and predisposes to infl ammation. These factors converge to hamper fi broblasts and endothelial cells proliferation, migration, homing, secretion and organization of a productive granulation tissue. Diabetic wound bed may turn chronically infl amed, pro-catabolic and a superimposed source of circulating pro-infl ammatory cytokines, establishing a self-perpetuating loop. Diabetic toxicity breadth includes mitochondrial damages in fi broblasts and endothelial cells becoming prone to apoptosis thus hindering granulation. Endothelial progenitor cells recruitment and tubulogenesis are also impaired. Failure of wound reepithelialization remains as a clinical challenge while it appears to be biologically multifactorial. Novel medical interventions as the local intra-ulcer infi ltration of epidermal growth factor have emerged to hopefully reduce the current worldwide amputation rates.