Role of iron deficiency and overload in the pathogenesis of diabetes and diabetic complications.

Iron is one of the essential minerals that are required for a variety of molecules to maintain their normal structures and functions and for cells to live, grow, and proliferate. The homeostasis of iron results from a tightly coordinated regulation by different proteins involved in uptake, excretion and intracellular storage/trafficking. Although it is essential, iron can also be toxic once in excess amounts. Through Fenton reaction, iron as a transit mineral can generate various reactive oxygen or nitrogen species; therefore, abnormal metabolism of iron can lead to several chronic pathogenesis. Oxidative stress is one of the major causative factors for diabetes and diabetic complications. Increasing evidence has indicated that iron overload not only increases risks of insulin resistance and diabetes, but also causes cardiovascular diseases in non-diabetic and diabetic subjects. Temporal iron deficiency was found to sensitize insulin action, but chronic iron deficiency with anemia can accelerate the development of cardiovascular diseases in non-diabetic and diabetic patients. In this review, therefore, we will first outline iron homeostasis, function, and toxicity, and then mainly summarize the data regarding the roles of iron deficiency and overload in the pathogenesis of diabetes and diabetic complications, as well as the possible links of iron to diabetes and diabetic complications. In the end, the possible therapy using iron chelators for diabetes and diabetic complications will also be discussed.