27-PUB: A Systematic Review on the Theranostic Potential of Iron in Diabetes

Background:Iron is an element now synonymous with inflammatory diseases, but in recent years it has shown potential in the pathophysiology of Diabetes. This review aims to cohesively analyze the association of serum iron in Diabetes and evaluate its clinical theranostic potential.

Method:Literature was obtained from PubMed, Embase, and Clinical Key. The search included Keywords,‘“DIABET” AND IRON’.

Result:21 papers were included in the review. Hemochromatosis is an established cause of type-1 and 2 diabetes. In recent years, several studies have found an increase in serum ferritin levels(Mean: 27.6%; Median: 11.9%) among diabetics, not associated with hemochromatosis. This can serve as a predictive marker for the development of microvascular complications in diabetes. The authors suggest this phenomenon may be the result of 2 mechanisms;(1) Hepcidin upregulation, and (2) Mild hemolysis due to increased osmotic fragility with HbA1c. The increased ferritin is associated with insulin resistance which may be attributed to ROS-induced mitochondrial fission. The authors suggest another cause may be apoferritin which stimulates PI3K, causing PDK1 activation and GLUT-4 translocation. This translocation is reduced with increased serum ferritin. Several animal studies have shown substantial improvement in glucose metabolism amongst diabetic mice on iron chelation therapy. Additionally, improved wound healing and nephropathy were found to be significant. Fernández-Real JM, et. al. in 2002, found that Phlebotomy(450mL ) increased insulin sensitivity amongst high ferritin (human)diabetics by 80.6 ± 43.2% from baseline at 4 months(P=0.0049). Iron chelation therapy is a promising potential adjuvant in high ferritin diabetes with microvascular complications, but adequate human trials have yet to be done.

Conclusion:In consideration of the available data, the authors believe that iron and iron chelation may serve an important low-cost effective role in the monitoring and therapeutics of diabetes.