Iron absorption in dysmetabolic iron overload syndrome is decreased and correlates with increased plasma hepcidin

Background/Aims The dysmetabolic iron overload syndrome (DIOS) is a common disorder but its origin remains unclear. Methods A case-control study was conducted to compare intestinal absorption of iron in 16 men with DIOS (age 53 ± 11 years, serum ferritin 750 ± 372 μg/l, hepatic iron 78 ± 25 μmol/g) and in 32 age-matched controls with normal body iron stores (16 overweight subjects and 16 lean subjects). Intestinal absorption was calculated as the area under the curve (AUC) of58 Fe administered orally and correlated with plasma hepcidin and with insulin resistance parameters including HOMA. Results Intestinal iron absorption was lower in DIOS (AUC = 22.4 ± 15.9 μg/l/h) compared to both overweight controls (AUC = 40.5 ± 29.4 μg/l/h, p = 0.04) and to lean controls (AUC = 102.5 ± 113.5 μg/l/h, p < 0.01). There was an inverse correlation between intestinal iron absorption and plasma hepcidin ( r = −0.61, p < 0.001), HOMA ( r = −0.35, p = 0.01) and C reactive protein ( r = −0.52, p < 0.001). Conclusions In overweight subjects with normal iron stores, iron absorption is decreased through hepcidin upregulation. In patients with DIOS, this decrease is more pronounced due to an additional effect of iron excess on circulating hepcidin levels.