Cross-Talk Between Iron Metabolism and Diabetes

Cross-Talk Between Iron Metabolism and Diabetes José Manuel Fernández-Real , Abel López-Bermejo and Wifredo Ricart From the Unit of Diabetes, Endocrinology and Nutrition, University Hospital of Girona “Dr Josep Trueta,” Girona, Spain Abstract Emerging scientific evidence has disclosed unsuspected influences between iron metabolism and type 2 diabetes. The relationship is bi-directional—iron affects glucose metabolism, and glucose metabolism impinges on several iron metabolic pathways. Oxidative stress and inflammatory cytokines influence these relationships, amplifying and potentiating the initiated events. The clinical impact of these interactions depends on both the genetic predisposition and the time frame in which this network of closely related signals acts. In recent years, increased iron stores have been found to predict the development of type 2 diabetes while iron depletion was protective. Iron-induced damage might also modulate the development of chronic diabetes complications. Iron depletion has been demonstrated to be beneficial in coronary artery responses, endothelial dysfunction, insulin secretion, insulin action, and metabolic control in type 2 diabetes. Here, we show that iron modulates insulin action in healthy individuals and in patients with type 2 diabetes. The extent of this influence should be tested in large-scale clinical trials, searching for the usefulness and cost-effectiveness of therapeutic measures that decrease iron toxicity. The study of individual susceptibility and of the mechanisms that influence tissue iron deposition and damage are proposed to be valuable in anticipating and treating diabetes complications. Footnotes Address correspondence and reprint requests to J.M. Fernández-Real, Unitat de Diabetes, Endocrinologia i Nutrició., Hospital de Girona “Dr Josep Trueta,” Avinguda de Francia s/n, 17007 Girona, Spain. E-mail: endocrino{at}htrueta.scs.es . Received for publication 12 February 2002 and accepted in revised form30 April 2002. BP, binding protein; CI, confidence interval; IRE, iron-regulatory element; IR-HIO, insulin resistance-associated hepatic iron overload; OR, odds ratio. DIABETES