Diabetes and hemochromatosis

Hereditary hemochromatosis is due, in most cases, to a common genetic mutation in the HFE gene which leads to the C282Y substitution, which in turn can result in end organ damage from iron overload. The major manifestations in advanced disease are skin pigmentation, diabetes ('bronzed diabetes') and cirrhosis of the liver. When present, these features are associated with a reduced life expectancy and the possibility of hepatocellular carcinoma. It may be considered as an endocrine disorder where, instead of insulin, the peptide hepcidin is deficient, leading to an unregulated increase in iron absorption from the intestine. When present, diabetes is due to a defect in beta cell function resulting from iron deposition in these cells. Increased insulin resistance may also be present in cases of advanced liver disease. Fortunately, patients are now more frequently being diagnosed at an earlier stage and have a good prognosis when appropriate treatment for the iron loading is instituted. In this situation, diabetes is less frequently seen. This review summarizes current knowledge about the pathogenesis of hereditary hemochromatosis, its association with diabetes mellitus and the management of these conditions