1.
Dysmetabolic Iron Overload in Metabolic Syndrome.
Sachinidis, A, Doumas, M, Imprialos, K, Stavropoulos, K, Katsimardou, A, Athyros, VG
Current pharmaceutical design. 2020;(10):1019-1024
Abstract
BACKGROUND We sought to determine the association of dysmetabolic iron overload syndrome (DIOS) with metabolic syndrome (MetS). METHODS Several studies have shown that DIOS is associated with Mets, mainly through the pathogenesis of its components: type 2 diabetes mellitus (T2DM), essential hypertension, non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (POS). RESULTS Serum ferritin levels increase proportionally according to the degree of insulin resistance (IR) and the number of components of Mets. Moreover, DIOS predicts the onset of T2DM and NAFLD. Dysregulation of iron metabolism in DIOS is due to a multifactorial and dynamic process triggered by an unhealthy diet, facilitated by environmental and genetic cofactors, and resulting in a bidirectional relation between the liver and visceral adipose tissue (VAT). Iron removal combined with a healthy diet improved both insulin sensitivity and beta-cell function, but had no significant effect on blood glucose; however, phlebotomy therapy might be considered with conflicting results. CONCLUSION Iron overload is closely associated with metabolic syndrome and its components; however, it remains under-appreciated in everyday clinical practice. Diet and lifestyle modification offer some clinical benefit; however, it is not adequate for successful management of the disease. The results of phlebotomy remain controversial, underlying the necessity of further efforts in this field.
2.
Dysmetabolic Hyperferritinemia and Dysmetabolic Iron Overload Syndrome (DIOS): Two Related Conditions or Different Entities?
Rametta, R, Fracanzani, AL, Fargion, S, Dongiovanni, P
Current pharmaceutical design. 2020;(10):1025-1035
Abstract
Hyperferritinemia is observed in one-third of patients with non-alcoholic fatty liver disease (NAFLD) and Metabolic Syndrome (MetS). The condition characterized by increased body iron stores associated with components of MetS has been defined as Dysmetabolic Iron Overload Syndrome (DIOS). DIOS represents the most frequent iron overload condition, since it is observed in 15% of patients with MetS and in half of those with NAFLD and its clinical presentation overlaps almost completely with that of dysmetabolic hyperferritinemia (DH). The pathogenetic mechanisms linking insulin resistance (IR), NAFLD and DIOS to iron overload are still debated. Hepcidin seems to play a role in iron accumulation in DIOS and NAFLD patients who show elevated serum hepcidin levels. The iron challenge does not restrain iron absorption despite adequate hepcidin production, suggesting that an impaired hepcidin activity rather than a deficit of hormone production underlies DIOS pathogenesis. Acquired and genetic factors are recognized to contribute to iron accumulation in NAFLD whereas additional studies are required to clearly demonstrate whether the same or different genetic factors lead to iron overload in DIOS. Finally, iron depletion by phlebotomy, together with the modification of diet and life-style habits, represents the therapeutic approach to decrease metabolic alterations and liver enzymes in NAFLD and DIOS patients. In this review, we summarized the current knowledge on the dysregulation of iron homeostasis in NAFLD and DIOS in the attempt to clarify whether they are different or more likely strictly related conditions, sharing the same pathogenic cause i.e. the MetS.
3.
[Myelodysplastic syndromes and iron metabolism].
Kawabata, H
[Rinsho ketsueki] The Japanese journal of clinical hematology. 2018;(10):2042-2049
Abstract
Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis in bone marrow and cytopenias in peripheral blood. In patients with MDS, iron overload is frequent due to red blood cell transfusions and ineffective erythropoiesis. Dysplastic erythroblasts in MDS secrete humoral factors such as erythroferrone, which suppress hepatic expression of hepcidin. Hepcidin is the key regulator of systemic iron homeostasis, and suppression of hepcidin expression leads to an increase in iron absorption from the intestines, exacerbating systemic iron overload. Patients with MDS with ring sideroblasts (MDS-RS) are prone to iron overload, with most harboring splicing factor 3B subunit 1 (SF3B1) mutations in hematopoietic cells. SF3B1 mutations may induce ring sideroblasts by downregulating ATP binding cassette subfamily B member 7, which exports iron-sulfur clusters from the mitochondria to the cytoplasm. Iron overload in MDS causes hepatic dysfunction, diabetes, cardiac failure, and atherosclerosis, whereas excess iron may suppress normal hematopoiesis. Though randomized control studies are lacking, results from retrospective and cohort studies indicate that iron chelation therapy is appropriate for lower-risk MSD patients with transfusion-related iron overload, although it is not recommended for higher-risk MSD patients with short life expectancy.