Potential role of increased iron stores in diabetes.

Diabetes mellitus (DM) is an important risk factor for the development of cardiovascular disease. Extensive clinical, epidemiologic, and basic studies suggest that excessive tissue iron stores may contribute to the occurrence and complications of DM. Secondary diabetes occurs in inherited pathologic iron overload syndromes of European- and African-derived populations and is an established complication of transfusional iron overload. Epidemiologic studies have repeatedly shown positive correlation between levels of serum ferritin and those of fasting glucose, insulin, and glycosylated hemoglobin. Iron reduction therapy in hereditary hemochromatosis and transfusional iron overload is associated with improved glucose tolerance and reduced incidence of secondary diabetes. Trials of iron reduction therapy in diabetes mellitus, although limited and inconclusive, have shown clinical improvement in some patients. The current article reviews evidence suggesting that tissue iron contributes to DM and its complications and presents preliminary data that emphasize the potential importance of iron overload in DM of African Americans.