Diabetes and haemochromatosis: current concepts, management and prevention.

Haemochromatosis is a common autosomal recessive disorder of iron metabolism caused by a gene in tight linkage with HLA class I genes. Despite intensive research, the molecular defect and underlying biochemical anomaly are still unknown. Diabetes, a serious complication of haemochromatosis, is frequently associated with cirrhosis which reduces life expectancy. Its development is related to iron excess, directly or through associated liver involvement, although the precise mechanisms of iron toxicity remain unclear. New concepts concerning its pathogenesis include insulin resistance and beta-cell dysfunction which are apparent well before insulin deficiency and can be reversed if iron depletion is promptly initiated. Today, earlier recognition of iron overload through active diagnostic approaches has a direct impact in reducing the frequency of diabetes among hemochromatosis patients. Presymptomatic diagnosis in the general population and among relatives of affected subjects currently relies on the detection of increased iron stores through medical awareness and family screening. Indirect gene diagnosis with serological and molecular markers of the HLA region can be provided for relatives of proven cases. As part of a genetic counselling process, this allows the identification of at-risk subjects before the onset of iron accumulation. Isolation of the gene and identification of the metabolic defect leading to increased iron absorption may have significant implications for future diagnostic procedures and preventive strategies in haemochromatosis.