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Review Article

Dysmetabolic Iron Overload in Metabolic Syndrome

Author(s): Alexandros Sachinidis, Michael Doumas, Konstantinos Imprialos, Konstantinos Stavropoulos, Alexandra Katsimardou and Vasilios G. Athyros *

Volume 26, Issue 10, 2020

Page: [1019 - 1024] Pages: 6

DOI: 10.2174/1381612826666200130090703

Price: $65

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.

Keywords: Serum ferritin, dysmetabolic iron overload syndrome, metabolic syndrome, insuline resistance, type two diabetes, arterial hypertension.

« Previous Next »
[1]
Hentze MW, Muckenthaler MU, Andrews NC. Balancing acts: molecular control of mammalian iron metabolism. Cell 2004; 117(3): 285-97.
[http://dx.doi.org/10.1016/S0092-8674(04)00343-5] [PMID: 15109490]
[2]
Mendler MH, Turlin B, Moirand R, et al. Insulin resistance-associated hepatic iron overload. Gastroenterology 1999; 117(5): 1155-63.
[http://dx.doi.org/10.1016/S0016-5085(99)70401-4] [PMID: 10535879]
[3]
Deugnier Y, Bardou-Jacquet É, Lainé F. Dysmetabolic iron overload syndrome (DIOS). Presse Med 2017; 46(12 Pt 2): e306-11.
[http://dx.doi.org/10.1016/j.lpm.2017.05.036] [PMID: 29169710]
[4]
Bozzini C, Girelli D, Olivieri O, et al. Prevalence of body iron excess in the metabolic syndrome. Diabetes Care 2005; 28(8): 2061-3.
[http://dx.doi.org/10.2337/diacare.28.8.2061] [PMID: 16043762]
[5]
Han LL, Wang YX, Li J, et al. Gender differences in associations of serum ferritin and diabetes, metabolic syndrome, and obesity in the China Health and Nutrition Survey. Mol Nutr Food Res 2014; 58(11): 2189-95.
[http://dx.doi.org/10.1002/mnfr.201400088] [PMID: 25163435]
[6]
Ford ES, Cogswell ME. Diabetes and serum ferritin concentration among U.S. adults. Diabetes Care 1999; 22(12): 1978-83.
[http://dx.doi.org/10.2337/diacare.22.12.1978] [PMID: 10587829]
[7]
Piperno A, Trombini P, Gelosa M, et al. Increased serum ferritin is common in men with essential hypertension. J Hypertens 2002; 20(8): 1513-8.
[http://dx.doi.org/10.1097/00004872-200208000-00013] [PMID: 12172312]
[8]
Bugianesi E, Manzini P, D’Antico S, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology 2004; 39(1): 179-87.
[http://dx.doi.org/10.1002/hep.20023] [PMID: 14752836]
[9]
Kowdley KV, Belt P, Wilson LA, et al. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2012; 55(1): 77-85.
[http://dx.doi.org/10.1002/hep.24706] [PMID: 21953442]
[10]
Valenti L, Fracanzani AL, Bugianesi E, et al. HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology 2010; 138(3): 905-12.
[http://dx.doi.org/10.1053/j.gastro.2009.11.013] [PMID: 19931264]
[11]
Botella-Carretero JI, Luque-Ramírez M, Alvarez-Blasco F, San Millán JL, Escobar-Morreale HF. Mutations in the hereditary hemochromatosis gene are not associated with the increased body iron stores observed in overweight and obese women with polycystic ovary syndrome. Diabetes Care 2006; 29(11): 2556.
[http://dx.doi.org/10.2337/dc06-1655] [PMID: 17065702]
[12]
Fernández-Real JM, Ricart-Engel W, Arroyo E, et al. Serum ferritin as a component of the insulin resistance syndrome. Diabetes Care 1998; 21(1): 62-8.
[http://dx.doi.org/10.2337/diacare.21.1.62] [PMID: 9580307]
[13]
Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB. Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA 2004; 291(6): 711-7.
[http://dx.doi.org/10.1001/jama.291.6.711] [PMID: 14871914]
[14]
Fumeron F, Péan F, Driss F, et al. Ferritin and transferrin are both predictive of the onset of hyperglycemia in men and women over 3 years: the data from an epidemiological study on the Insulin Resistance Syndrome (DESIR) study. Diabetes Care 2006; 29(9): 2090-4.
[http://dx.doi.org/10.2337/dc06-0093] [PMID: 16936158]
[15]
Kim CW, Chang Y, Sung E, Shin H, Ryu S. Serum ferritin levels predict incident non-alcoholic fatty liver disease in healthy Korean men. Metabolism 2012; 61(8): 1182-8.
[http://dx.doi.org/10.1016/j.metabol.2012.01.007] [PMID: 22386931]
[16]
Adams PC, Barton JC. A diagnostic approach to hyperferritinemia with a non-elevated transferrin saturation. J Hepatol 2011; 55(2): 453-8.
[http://dx.doi.org/10.1016/j.jhep.2011.02.010] [PMID: 21354228]
[17]
Jézéquel C, Lainé F, Laviolle B, Kiani A, Bardou-Jacquet E, Deugnier Y. Both hepatic and body iron stores are increased in dysmetabolic iron overload syndrome. A case-control study. PLoS One 2015; 10(6): e0128530
[http://dx.doi.org/10.1371/journal.pone.0128530] [PMID: 26030828]
[18]
Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet 2016; 388(10045): 706-16.
[http://dx.doi.org/10.1016/S0140-6736(15)01315-X] [PMID: 26975792]
[19]
Lainé F, Jouannolle AM, Morcet J, et al. Phenotypic expression in detected C282Y homozygous women depends on body mass index. J Hepatol 2005; 43(6): 1055-9.
[http://dx.doi.org/10.1016/j.jhep.2005.05.027] [PMID: 16139917]
[20]
Lainé F, Deugnier Y. Increased expression of hepcidin in obese patients: impact on phenotypic expression of hemochromatosis and pathophysiology of dysmetabolic iron overload syndrome. Gastroenterology 2006; 131(6): 2028.
[http://dx.doi.org/10.1053/j.gastro.2006.10.046] [PMID: 17188970]
[21]
Gandon Y, Olivié D, Guyader D, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004; 363(9406): 357-62.
[http://dx.doi.org/10.1016/S0140-6736(04)15436-6] [PMID: 15070565]
[22]
Roblin X, Phelip JM, Hilleret MN, Heluwaert F, Bonaz B, Zarski JP. [Correction of insulin resistance syndrome does not cause normalisation of hyperferritinaemia]. Gastroenterol Clin Biol 2003; 27(12): 1079-83.
[PMID: 14770107]
[23]
Alberti KG, Zimmet P, Shaw J. Metabolic syndrome - A new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med 2006; 23(5): 469-80.
[http://dx.doi.org/10.1111/j.1464-5491.2006.01858.x] [PMID: 16681555]
[24]
Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120(16): 1640-5.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192644] [PMID: 19805654]
[25]
Sullivan JL. Iron and the sex difference in heart disease risk. Lancet 1981; 1(8233): 1293-4.
[http://dx.doi.org/10.1016/S0140-6736(81)92463-6] [PMID: 6112609]
[26]
Wood RJ. The iron-heart disease connection: is it dead or just hiding? Ageing Res Rev 2004; 3(3): 355-67.
[http://dx.doi.org/10.1016/j.arr.2004.04.002] [PMID: 15231242]
[27]
Lao TT, Chan PL, Tam KF. Gestational diabetes mellitus in the last trimester - a feature of maternal iron excess? Diabet Med 2001; 18(3): 218-23.
[http://dx.doi.org/10.1046/j.1464-5491.2001.00453.x] [PMID: 11318843]
[28]
Iwasaki T, Nakajima A, Yoneda M, et al. Serum ferritin is associated with visceral fat area and subcutaneous fat area. Diabetes Care 2005; 28(10): 2486-91.
[http://dx.doi.org/10.2337/diacare.28.10.2486] [PMID: 16186284]
[29]
Fernández-Real JM, López-Bermejo A, Ricart W. Iron stores, blood donation, and insulin sensitivity and secretion. Clin Chem 2005; 51(7): 1201-5.
[http://dx.doi.org/10.1373/clinchem.2004.046847] [PMID: 15976100]
[30]
Wrede CE, Buettner R, Bollheimer LC, Schölmerich J, Palitzsch KD, Hellerbrand C. Association between serum ferritin and the insulin resistance syndrome in a representative population. Eur J Endocrinol 2006; 154(2): 333-40.
[http://dx.doi.org/10.1530/eje.1.02083] [PMID: 16452549]
[31]
Galan P, Noisette N, Estaquio C, et al. Serum ferritin, cardiovascular risk factors and ischaemic heart diseases: a prospective analysis in the SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) cohort. Public Health Nutr 2006; 9(1): 70-4.
[http://dx.doi.org/10.1079/PHN2005826] [PMID: 16480536]
[32]
Dubern B, Girardet JP, Tounian P. Insulin resistance and ferritin as major determinants of abnormal serum aminotransferase in severely obese children. Int J Pediatr Obes 2006; 1(2): 77-82.
[http://dx.doi.org/10.1080/17477160600569594] [PMID: 17907318]
[33]
Aigner E, Hinz C, Steiner K, et al. Iron stores, liver transaminase levels and metabolic risk in healthy teenagers. Eur J Clin Invest 2010; 40(2): 155-63.
[http://dx.doi.org/10.1111/j.1365-2362.2009.02238.x] [PMID: 20050877]
[34]
Martínez-García MA, Luque-Ramírez M, San-Millán JL, Escobar-Morreale HF. Body iron stores and glucose intolerance in premenopausal women: role of hyperandrogenism, insulin resistance, and genomic variants related to inflammation, oxidative stress, and iron metabolism. Diabetes Care 2009; 32(8): 1525-30.
[http://dx.doi.org/10.2337/dc09-0420] [PMID: 19401444]
[35]
Luque-Ramírez M, Alvarez-Blasco F, Botella-Carretero JI, Sanchón R, San Millán JL, Escobar-Morreale HF. Increased body iron stores of obese women with polycystic ovary syndrome are a consequence of insulin resistance and hyperinsulinism and are not a result of reduced menstrual losses. Diabetes Care 2007; 30(9): 2309-13.
[http://dx.doi.org/10.2337/dc07-0642] [PMID: 17536071]
[36]
Ramakrishnan U, Kuklina E, Stein AD. Iron stores and cardiovascular disease risk factors in women of reproductive age in the United States. Am J Clin Nutr 2002; 76(6): 1256-60.
[http://dx.doi.org/10.1093/ajcn/76.6.1256] [PMID: 12450891]
[37]
Dongiovanni P, Valenti L, Ludovica Fracanzani A, Gatti S, Cairo G, Fargion S. Iron depletion by deferoxamine up-regulates glucose uptake and insulin signaling in hepatoma cells and in rat liver. Am J Pathol 2008; 172(3): 738-47.
[http://dx.doi.org/10.2353/ajpath.2008.070097] [PMID: 18245813]
[38]
Green A, Basile R, Rumberger JM. Transferrin and iron induce insulin resistance of glucose transport in adipocytes. Metabolism 2006; 55(8): 1042-5.
[http://dx.doi.org/10.1016/j.metabol.2006.03.015] [PMID: 16839839]
[39]
Rumberger JM, Peters T Jr, Burrington C, Green A. Transferrin and iron contribute to the lipolytic effect of serum in isolated adipocytes. Diabetes 2004; 53(10): 2535-41.
[http://dx.doi.org/10.2337/diabetes.53.10.2535] [PMID: 15448081]
[40]
Aso Y, Takebayashi K, Wakabayashi S, et al. Relation between serum high molecular weight adiponectin and serum ferritin or prohepcidin in patients with type 2 diabetes. Diabetes Res Clin Pract 2010; 90(3): 250-5.
[http://dx.doi.org/10.1016/j.diabres.2010.09.008] [PMID: 20888657]
[41]
Ku BJ, Kim SY, Lee TY, Park KS. Serum ferritin is inversely correlated with serum adiponectin level: population-based cross-sectional study. Dis Markers 2009; 27(6): 303-10.
[http://dx.doi.org/10.1155/2009/931082] [PMID: 20075513]
[42]
Gabrielsen JS, Gao Y, Simcox JA, et al. Adipocyte iron regulates adiponectin and insulin sensitivity. J Clin Invest 2012; 122(10): 3529-40.
[http://dx.doi.org/10.1172/JCI44421] [PMID: 22996660]
[43]
Gao Y, Li Z, Gabrielsen JS, et al. Adipocyte iron regulates leptin and food intake. J Clin Invest 2015; 125(9): 3681-91.
[http://dx.doi.org/10.1172/JCI81860] [PMID: 26301810]
[44]
Dongiovanni P, Fracanzani AL, Fargion S, Valenti L. Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target. J Hepatol 2011; 55(4): 920-32.
[http://dx.doi.org/10.1016/j.jhep.2011.05.008] [PMID: 21718726]
[45]
Fernández-Real JM, Moreno JM, Chico B, López-Bermejo A, Ricart W. Circulating visfatin is associated with parameters of iron metabolism in subjects with altered glucose tolerance. Diabetes Care 2007; 30(3): 616-21.
[http://dx.doi.org/10.2337/dc06-1581] [PMID: 17327330]
[46]
Fernández-Real JM, Moreno JM, Ricart W. Circulating retinol-binding protein-4 concentration might reflect insulin resistance-associated iron overload. Diabetes 2008; 57(7): 1918-25.
[http://dx.doi.org/10.2337/db08-0041] [PMID: 18426863]
[47]
Datz C, Felder TK, Niederseer D, Aigner E. Iron homeostasis in the metabolic syndrome. Eur J Clin Invest 2013; 43(2): 215-24.
[http://dx.doi.org/10.1111/eci.12032] [PMID: 23289518]
[48]
Handa P, Morgan-Stevenson V, Maliken BD, et al. Iron overload results in hepatic oxidative stress, immune cell activation, and hepatocellular ballooning injury, leading to nonalcoholic steatohepatitis in genetically obese mice. Am J Physiol Gastrointest Liver Physiol 2016; 310(2): G117-27.
[http://dx.doi.org/10.1152/ajpgi.00246.2015] [PMID: 26564716]
[49]
Sutti S, Jindal A, Locatelli I, et al. Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH. Hepatology 2014; 59(3): 886-97.
[http://dx.doi.org/10.1002/hep.26749] [PMID: 24115128]
[50]
Gautier A, Laine F, Massart C, et al. Liver iron overload is associated with elevated SHBG concentration and moderate hypogonadotrophic hypogonadism in dysmetabolic men without genetic haemochromatosis. European journal of endocrinology / European Federation of Endocrine Societies 2011; 165: 339-43.
[http://dx.doi.org/10.1530/EJE-11-0215]
[51]
Dhindsa S, Ghanim H, Batra M, et al. Effect of testosterone on hepcidin, ferroportin, ferritin and iron binding capacity in patients with hypogonadotropic hypogonadism and type 2 diabetes. Clin Endocrinol (Oxf) 2016; 85(5): 772-80.
[http://dx.doi.org/10.1111/cen.13130] [PMID: 27292585]
[52]
Fargion S, Mattioli M, Fracanzani AL, et al. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol 2001; 96(8): 2448-55.
[http://dx.doi.org/10.1111/j.1572-0241.2001.04052.x] [PMID: 11513189]
[53]
George DK, Goldwurm S, MacDonald GA, et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998; 114(2): 311-8.
[http://dx.doi.org/10.1016/S0016-5085(98)70482-2] [PMID: 9453491]
[54]
Fierbinţeanu-Braticevici C, Bengus A, Neamţu M, Usvat R. The risk factors of fibrosis in nonalcoholic steatohepatitis. Rom J Intern Med 2002; 40(1-4): 81-8.
[PMID: 15526543]
[55]
Valenti L, Dongiovanni P, Fracanzani AL, et al. Increased susceptibility to nonalcoholic fatty liver disease in heterozygotes for the mutation responsible for hereditary hemochromatosis. Dig Liver Dis 2003; 35(3): 172-8.
[http://dx.doi.org/10.1016/S1590-8658(03)00025-2] [PMID: 12779071]
[56]
Chitturi S, Weltman M, Farrell GC, et al. HFE mutations, hepatic iron, and fibrosis: ethnic-specific association of NASH with C282Y but not with fibrotic severity. Hepatology 2002; 36(1): 142-9.
[http://dx.doi.org/10.1053/jhep.2002.33892] [PMID: 12085358]
[57]
Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129(1): 113-21.
[http://dx.doi.org/10.1053/j.gastro.2005.04.014] [PMID: 16012941]
[58]
Sorrentino P, D’Angelo S, Ferbo U, Micheli P, Bracigliano A, Vecchione R. Liver iron excess in patients with hepatocellular carcinoma developed on non-alcoholic steato-hepatitis. J Hepatol 2009; 50(2): 351-7.
[http://dx.doi.org/10.1016/j.jhep.2008.09.011] [PMID: 19070395]
[59]
Hernaez R, Yeung E, Clark JM, Kowdley KV, Brancati FL, Kao WH. Hemochromatosis gene and nonalcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 2011; 55(5): 1079-85.
[http://dx.doi.org/10.1016/j.jhep.2011.02.013] [PMID: 21354231]
[60]
Valenti L, Canavesi E, Galmozzi E, et al. Beta-globin mutations are associated with parenchymal siderosis and fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol 2010; 53(5): 927-33.
[http://dx.doi.org/10.1016/j.jhep.2010.05.023] [PMID: 20739079]
[61]
Nelson JE, Brunt EM, Kowdley KV. Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations. Hepatology 2012; 56(5): 1730-40.
[http://dx.doi.org/10.1002/hep.25856] [PMID: 22611049]
[62]
Aigner E, Theurl I, Theurl M, et al. Pathways underlying iron accumulation in human nonalcoholic fatty liver disease. Am J Clin Nutr 2008; 87(5): 1374-83.
[http://dx.doi.org/10.1093/ajcn/87.5.1374] [PMID: 18469261]
[63]
Barisani D, Pelucchi S, Mariani R, et al. Hepcidin and iron-related gene expression in subjects with Dysmetabolic Hepatic Iron Overload. J Hepatol 2008; 49(1): 123-33.
[http://dx.doi.org/10.1016/j.jhep.2008.03.011] [PMID: 18462824]
[64]
Aigner E, Weiss G, Datz C. Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver. World J Hepatol 2015; 7(2): 177-88.
[http://dx.doi.org/10.4254/wjh.v7.i2.177] [PMID: 25729473]
[65]
Dallalio G, Law E, Means RT Jr. Hepcidin inhibits in vitro erythroid colony formation at reduced erythropoietin concentrations. Blood 2006; 107(7): 2702-4.
[http://dx.doi.org/10.1182/blood-2005-07-2854] [PMID: 16332970]
[66]
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005; 352(10): 1011-23.
[http://dx.doi.org/10.1056/NEJMra041809] [PMID: 15758012]
[67]
Aigner E, Theurl I, Haufe H, et al. Copper availability contributes to iron perturbations in human nonalcoholic fatty liver disease. Gastroenterology 2008; 135(2): 680-8.
[http://dx.doi.org/10.1053/j.gastro.2008.04.007] [PMID: 18505688]
[68]
Zoller H, Koch RO, Theurl I, et al. Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload. Gastroenterology 2001; 120(6): 1412-9.
[http://dx.doi.org/10.1053/gast.2001.24033] [PMID: 11313311]
[69]
Ruivard M, Lainé F, Ganz T, et al. Iron absorption in dysmetabolic iron overload syndrome is decreased and correlates with increased plasma hepcidin. J Hepatol 2009; 50(6): 1219-25.
[http://dx.doi.org/10.1016/j.jhep.2009.01.029] [PMID: 19398238]
[70]
Rametta R, Dongiovanni P, Pelusi S, et al. Hepcidin resistance in dysmetabolic iron overload. Liver international: Official journal of the International Association for the Study of the Liver 2016; 36: 1540-8.
[http://dx.doi.org/10.1111/liv.13124]
[71]
Zimmermann MB, Zeder C, Muthayya S, et al. Adiposity in women and children from transition countries predicts decreased iron absorption, iron deficiency and a reduced response to iron fortification. Int J Obes 2008; 32(7): 1098-104.
[http://dx.doi.org/10.1038/ijo.2008.43] [PMID: 18427564]
[72]
Sonnweber T, Ress C, Nairz M, et al. High-fat diet causes iron deficiency via hepcidin-independent reduction of duodenal iron absorption. J Nutr Biochem 2012; 23(12): 1600-8.
[http://dx.doi.org/10.1016/j.jnutbio.2011.10.013] [PMID: 22444869]
[73]
Michalaki MA, Vagenakis AG, Leonardou AS, et al. Thyroid function in humans with morbid obesity. Thyroid 2006; 16: 73e8
[http://dx.doi.org/10.1089/thy.2006.16.73]
[74]
Bastemir M, Akin F, Alkis E, Kaptanoglu B. Obesity is associated with increased serum TSH level, independent of thyroid function. Swiss Med Wkly 2007; 137: 431e4
[75]
Stichel H, I'Allemand D, Gruter A. Thyroid function and obesity in children and adolescents. Horm Res 2000; 54: 14e9-.
[76]
Bhowmick SK, Dasari G, Levens KL, Rettig KR. The prevalence of elevated serum thyroid-stimulating hormone in childhood/ adolescent obesity and of autoimmune thyroid diseases in a subgroup. J Natl Med Assoc 2007; 99: 773e6
[77]
Lapenna D, Pierdomenico SD, Ciofani G, et al. Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques. Free Radic Biol Med 2007; 42(4): 492-8.
[http://dx.doi.org/10.1016/j.freeradbiomed.2006.11.014] [PMID: 17275681]
[78]
Ganz T, Nemeth E. Iron imports. IV. Hepcidin and regulation of body iron metabolism. Am J Physiol Gastrointest Liver Physiol 2006; 290(2): G199-203.
[http://dx.doi.org/10.1152/ajpgi.00412.2005] [PMID: 16407589]
[79]
Lee TS, Shiao MS, Pan CC, Chau LY. Iron-deficient diet reduces atherosclerotic lesions in apoE-deficient mice. Circulation 1999; 99(9): 1222-9.
[http://dx.doi.org/10.1161/01.CIR.99.9.1222] [PMID: 10069791]
[80]
Zacharski LR, Chow BK, Howes PS, et al. Reduction of iron stores and cardiovascular outcomes in patients with peripheral arterial disease: a randomized controlled trial. JAMA 2007; 297(6): 603-10.
[http://dx.doi.org/10.1001/jama.297.6.603] [PMID: 17299195]
[81]
van der A DL, Peeters PH, Grobbee DE, et al. HFE mutations and risk of coronary heart disease in middle-aged women. Eur J Clin Invest 2006; 36(10): 682-90.
[http://dx.doi.org/10.1111/j.1365-2362.2006.01711.x] [PMID: 16968463]
[82]
Pardo Silva MC, Njajou OT, Alizadeh BZ, et al. HFE gene mutations increase the risk of coronary heart disease in women. Eur J Epidemiol 2010; 25(9): 643-9.
[http://dx.doi.org/10.1007/s10654-010-9489-6] [PMID: 20640879]
[83]
Danesh J, Appleby P. Coronary heart disease and iron status: meta-analyses of prospective studies. Circulation 1999; 99(7): 852-4.
[http://dx.doi.org/10.1161/01.CIR.99.7.852] [PMID: 10027804]
[84]
Sullivan JL. Macrophage iron, hepcidin, and atherosclerotic plaque stability. Exp Biol Med (Maywood) 2007; 232(8): 1014-20.
[http://dx.doi.org/10.3181/0703-MR-54] [PMID: 17720947]
[85]
Theurl I, Theurl M, Seifert M, et al. Autocrine formation of hepcidin induces iron retention in human monocytes. Blood 2008; 111(4): 2392-9.
[http://dx.doi.org/10.1182/blood-2007-05-090019] [PMID: 18073346]
[86]
Hua NW, Stoohs RA, Facchini FS. Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians. Br J Nutr 2001; 86(4): 515-9.
[http://dx.doi.org/10.1079/BJN2001421] [PMID: 11591239]
[87]
Lainé F, Ruivard M, Loustaud-Ratti V, et al. Metabolic and hepatic effects of bloodletting in dysmetabolic iron overload syndrome: A randomized controlled study in 274 patients. Hepatology 2017; 65(2): 465-74.
[http://dx.doi.org/10.1002/hep.28856] [PMID: 27685251]
[88]
Fernández-Real JM, Peñarroja G, Castro A, García-Bragado F, Hernández-Aguado I, Ricart W. Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and beta-cell function. Diabetes 2002; 51(4): 1000-4.
[http://dx.doi.org/10.2337/diabetes.51.4.1000] [PMID: 11916918]
[89]
Facchini FS, Hua NW, Stoohs RA. Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease. Gastroenterology 2002; 122(4): 931-9.
[http://dx.doi.org/10.1053/gast.2002.32403] [PMID: 11910345]
[90]
Houschyar KS, Lüdtke R, Dobos GJ, et al. Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: results from a randomized clinical trial. BMC Med 2012; 10: 54.
[http://dx.doi.org/10.1186/1741-7015-10-54] [PMID: 22647517]
[91]
Valenti L, Fracanzani AL, Dongiovanni P, et al. Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case-control study. Am J Gastroenterol 2007; 102(6): 1251-8.
[http://dx.doi.org/10.1111/j.1572-0241.2007.01192.x] [PMID: 17391316]
[92]
Valenti L, Fracanzani AL, Dongiovanni P, et al. A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia. World J Gastroenterol 2014; 20(11): 3002-10.
[http://dx.doi.org/10.3748/wjg.v20.i11.3002] [PMID: 24659891]
[93]
Beaton MD, Chakrabarti S, Levstik M, Speechley M, Marotta P, Adams P. Phase II clinical trial of phlebotomy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2013; 37(7): 720-9.
[http://dx.doi.org/10.1111/apt.12255] [PMID: 23441892]
[94]
Adams LA, Crawford DH, Stuart K, et al. The impact of phlebotomy in nonalcoholic fatty liver disease: A prospective, randomized, controlled trial. Hepatology 2015; 61(5): 1555-64.
[http://dx.doi.org/10.1002/hep.27662] [PMID: 25524401]
[95]
Lainé F, Bendavid C, Moirand R, et al. Prediction of liver fibrosis in patients with features of the metabolic syndrome regardless of alcohol consumption. Hepatology 2004; 39(6): 1639-46.
[http://dx.doi.org/10.1002/hep.20219] [PMID: 15185305]
[96]
Piperno A, Vergani A, Salvioni A, et al. Effects of venesections and restricted diet in patients with the insulin-resistance hepatic iron overload syndrome. Liver international: official journal of the International Association for the Study of the Liver 2004; 24: 471-6.
[http://dx.doi.org/10.1111/j.1478-3231.2004.0988.x]

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