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Current Medicinal Chemistry

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Systematic Review Article

Serum Hepcidin, the Hepcidin/Ferritin Ratio and the Risk of Type 2 Diabetes: A Systematic Review and Meta-Analysis

Author(s): Nahid Karamzad, Aziz Eftekhari, Ahad Ashrafi-Asgarabad, Mark J.M. Sullman, Amirhossein Sahebkar and Saeid Safiri*

Volume 28, Issue 6, 2021

Published on: 07 February, 2020

Page: [1224 - 1233] Pages: 10

DOI: 10.2174/0929867327666200207120158

Price: $65

Abstract

Objectives: To perform a meta-analysis on the relationship type 2 diabetes has with serum hepcidin and the hepcidin/ferritin ratio.

Methods: The following databases were searched using all relevant keywords: Web of Science, Medline, Scopus, Embase and Google Scholar. All studies that examined the relationship type 2 diabetes has with serum hepcidin or the hepcidin/ferritin ratio were included in this meta-analysis and systematic review provided, were published in English between 2011 and 2018. A random-effects model was used to pool the standardized mean difference (SMD).

Results: The SMD of serum hepcidin among patients with type 2 diabetes and healthy controls were compared across eight studies (n cases=878; n controls=2306). The pooled SMD of serum hepcidin did not differ significantly between study groups (SMD: 0.04; 95% confidence interval (CI): -0.29 to 0.35). In contrast, the serum hepcidin/ferritin ratio was examined across five studies (n cases=229; n controls=1426) and was found to be negatively associated with the risk of type 2 diabetes (SMD: -0.52; 95% confidence interval (CI): -0.85 to -0.19). There was no publication bias found for the associations serum hepcidin (Egger´s test: P =0.97) or the hepcidin/ferritin ratio (Egger´s test: P =0.75) had with type 2 diabetes.

Conclusion: Although hepcidin has been proposed as a risk marker for type 2 diabetes, our metaanalysis found that the hepcidin/ferritin ratio was superior to hepcidin alone as a risk marker.

Keywords: Type 2 diabetes mellitus, hepcidins, ferritins, risk marker, meta-analysis, Serum Hepcidin, Hepcidin/ Ferritin Ratio, study groups.

« Previous Next »
[1]
Kirii, K.; Mizoue, T.; Iso, H.; Takahashi, Y.; Kato, M.; Inoue, M.; Noda, M.; Tsugane, S. Japan Public Health Center-based Prospective Study Group. Calcium, vitamin D and dairy intake in relation to type 2 diabetes risk in a Japanese cohort. Diabetologia, 2009, 52(12), 2542-2550.
[http://dx.doi.org/10.1007/s00125-009-1554-x] [PMID: 19823801]
[2]
Vela, D.; Sopi, R.B.; Mladenov, M. Low hepcidin in diabetes mellitus: examining the molecular links and their clinical implications. Can. J. Diabetes, 2018, 42(2), 179-187.
[http://dx.doi.org/10.1016/j.jcjd.2017.04.007]] [PMID: 28662967]
[3]
Aregbesola, A.; Voutilainen, S.; Virtanen, J.K.; Aregbesola, A.; Tuomainen, T-P. Serum hepcidin concentrations and type 2 diabetes. World J. Diabetes, 2015, 6(7), 978-982.
[http://dx.doi.org/10.4239/wjd.v6.i7.978] [PMID: 26185605]
[4]
Derbent, A.U.; Simavli, S.A.; Kaygusuz, I.; Gumus, I.I.; Yılmaz, S.; Yildirim, M.; Uysal, S. Serum hepcidin is associated with parameters of glucose metabolism in women with gestational diabetes mellitus. J. Matern. Fetal Neonatal Med., 2013, 26(11), 1112-1115.
[http://dx.doi.org/10.3109/14767058.2013.770462] [PMID: 23356500]
[5]
Guo, L-N.; Yang, Y-Z.; Feng, Y-Z. Serum and salivary ferritin and Hepcidin levels in patients with chronic periodontitis and type 2 diabetes mellitus. BMC Oral Health, 2018, 18(1), 63.
[http://dx.doi.org/10.1186/s12903-018-0524-4] [PMID: 29636044]
[6]
Sam, A.H.; Busbridge, M.; Amin, A.; Webber, L.; White, D.; Franks, S.; Martin, N.M.; Sleeth, M.; Ismail, N.A.; Daud, N.M.; Papamargaritis, D.; Le Roux, C.W.; Chapman, R.S.; Frost, G.; Bloom, S.R.; Murphy, K.G. Hepcidin levels in diabetes mellitus and polycystic ovary syndrome. Diabet. Med., 2013, 30(12), 1495-1499.
[http://dx.doi.org/10.1111/dme.12262] [PMID: 23796160]
[7]
Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G.; Group, P. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med., 2009, 6(7)e1000097
[http://dx.doi.org/10.1371/journal.pmed.1000097] [PMID: 19621072]
[8]
Vandenbroucke, J.P.; von Elm, E.; Altman, D.G.; Gøtzsche, P.C.; Mulrow, C.D.; Pocock, S.J.; Poole, C.; Schlesselman, J.J.; Egger, M.; Initiative, S. STROBE initiative. Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration. PLoS Med., 2007, 4(10)e297
[http://dx.doi.org/10.1371/journal.pmed.0040297] [PMID: 17941715]
[9]
Modesti, P.A.; Reboldi, G.; Cappuccio, F.P.; Agyemang, C.; Remuzzi, G.; Rapi, S.; Perruolo, E.; Parati, G. ESH Working Group on CV Risk in Low Resource Settings. Panethnic differences in blood pressure in Europe: a systematic review and meta-analysis. PLoS One, 2016, 11(1)e0147601
[http://dx.doi.org/10.1371/journal.pone.0147601] [PMID: 26808317]
[10]
Wells, G.A.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2018. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (Access date December 10 2020
[11]
Egger, M.; Smith, G.D.; Schneider, M.; Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109), 629-634.
[http://dx.doi.org/10.1136/bmj.315.7109.629] [PMID: 9310563]
[12]
Aso, Y.; Takebayashi, K.; Wakabayashi, S.; Momobayashi, A.; Sugawara, N.; Terasawa, T.; Naruse, R.; Hara, K.; Suetsugu, M.; Morita, K.; Inukai, T. 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), 250-255.
[http://dx.doi.org/10.1016/j.diabres.2010.09.008] [PMID: 20888657]
[13]
Park, C.H.; Valore, E.V.; Waring, A.J.; Ganz, T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J. Biol. Chem., 2001, 276(11), 7806-7810.
[http://dx.doi.org/10.1074/jbc.M008922200] [PMID: 11113131]
[14]
Koenig, M.D.; Tussing-Humphreys, L.; Day, J.; Cadwell, B.; Nemeth, E. Hepcidin and iron homeostasis during pregnancy. Nutrients, 2014, 6(8), 3062-3083.
[http://dx.doi.org/10.3390/nu6083062] [PMID: 25093277]
[15]
Birkenfeld, A.L.; Shulman, G.I. Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology, 2014, 59(2), 713-723.
[http://dx.doi.org/10.1002/hep.26672] [PMID: 23929732]
[16]
Del Prato, S.; Bianchi, C.; Dardano, A.; Miccoli, R. Insulin as an early treatment for type 2 diabetes: ORIGIN or end of an old question? Diabetes Care, 2013, 36(Suppl. 2), S198-S204.
[http://dx.doi.org/10.2337/dcS13-2019] [PMID: 23882046]
[17]
Knight, Z.A.; Schmidt, S.F.; Birsoy, K.; Tan, K.; Friedman, J.M. A critical role for mTORC1 in erythropoiesis and anemia. eLife, 2014, 3e01913
[http://dx.doi.org/10.7554/eLife.01913] [PMID: 25201874]
[18]
Silvestri, L.; Colucci, S.; Pagani, A.; Artuso, I.; Pettinato, M.; Nai, A.; Camaschella, C. A novel crosstalk between iron homeostasis and mTOR mediated by the immunophilin FKBP12. Am. Soc. Hematol.,, 2016..
[http://dx.doi.org/10.1182/blood.V128.22.261.261]
[19]
Zhang, W.; Thompson, B.J.; Hietakangas, V.; Cohen, S.M. MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila. PLoS Genet., 2011, 7(12)e1002429
[http://dx.doi.org/10.1371/journal.pgen.1002429] [PMID: 22242005]
[20]
Rothman, K.J.; Greenland, S.; Lash, T.L. Modern epidemiology, 3rd Edition; Lippincott Williams & Wilkins: Philadelphia, 2008.
[21]
Haap, M.; Fritsche, A.; Mensing, H.J.; Häring, H-U.; Stumvoll, M. Association of high serum ferritin concentration with glucose intolerance and insulin resistance in healthy people. Ann. Intern. Med., 2003, 139(10), 869-871.
[http://dx.doi.org/10.7326/0003-4819-139-10-200311180-00029] [PMID: 14623634]
[22]
Fernández-Real, J-M.; Ricart-Engel, W.; Arroyo, E.; Balançá, R.; Casamitjana-Abella, R.; Cabrero, D.; Fernández-Castañer, M.; Soler, J. Serum ferritin as a component of the insulin resistance syndrome. Diabetes Care, 1998, 21(1), 62-68.
[http://dx.doi.org/10.2337/diacare.21.1.62] [PMID: 9580307]
[23]
Tuomainen, T-P.; Nyyssönen, K.; Salonen, R.; Tervahauta, A.; Korpela, H.; Lakka, T.; Kaplan, G.A.; Salonen, J.T. Body iron stores are associated with serum insulin and blood glucose concentrations. Population study in 1,013 eastern Finnish men. Diabetes Care, 1997, 20(3), 426-428.
[http://dx.doi.org/10.2337/diacare.20.3.426] [PMID: 9051399]
[24]
Mainous, A.G., III; Wells, B.J.; Everett, C.J.; Gill, J.M.; King, D.E. Association of ferritin and lipids with C-reactive protein. Am. J. Cardiol., 2004, 93(5), 559-562.
[http://dx.doi.org/10.1016/j.amjcard.2003.11.018] [PMID: 14996579]
[25]
Sherwood, R.A.; Pippard, M.J.; Peters, T.J. Iron homeostasis and the assessment of iron status. Ann. Clin. Biochem., 1998, 35(Pt 6), 693-708.
[http://dx.doi.org/10.1177/000456329803500601] [PMID: 9838982]
[26]
Chang, J.; Bird, R.; Clague, A.; Carter, A. Clinical utility of serum soluble transferrin receptor levels and comparison with bone marrow iron stores as an index for iron-deficient erythropoiesis in a heterogeneous group of patients. Pathology, 2007, 39(3), 349-353.
[http://dx.doi.org/10.1080/00313020701329732] [PMID: 17558864]
[27]
Chen, X.; Scholl, T.O.; Stein, T.P. Association of elevated serum ferritin levels and the risk of gestational diabetes mellitus in pregnant women: The Camden study. Diabetes Care, 2006, 29(5), 1077-1082.
[http://dx.doi.org/10.2337/dc06-0164] [PMID: 16644640]
[28]
Jiang, F.; Sun, Z-Z.; Tang, Y-T.; Xu, C.; Jiao, X-Y. Hepcidin expression and iron parameters change in Type 2 diabetic patients. Diabetes Res. Clin. Pract., 2011, 93(1), 43-48.
[http://dx.doi.org/10.1016/j.diabres.2011.03.028] [PMID: 21513996]
[29]
Ramos, E.; Ruchala, P.; Goodnough, J.B.; Kautz, L.; Preza, G.C.; Nemeth, E.; Ganz, T.J.B. Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis., 2012, 120(48), 3829-3836.
[http://dx.doi.org/10.1182/blood-2012-07-440743]
[30]
Suárez-Ortegón, M.F.; Moreno, M.; Arbeláez, A.; Xifra, G.; Mosquera, M.; Moreno-Navarrete, J.M.; Aguilar-de Plata, C.; Esteve, E.; Ricart, W.; Fernández-Real, J.M. Circulating hepcidin in type 2 diabetes: A multivariate analysis and double blind evaluation of metformin effects. Mol. Nutr. Food Res., 2015, 59(12), 2460-2470.
[http://dx.doi.org/10.1002/mnfr.201500310] [PMID: 26394887]
[31]
Andrews, M.; Soto, N.; Arredondo-Olguín, M. Association between ferritin and hepcidin levels and inflammatory status in patients with type 2 diabetes mellitus and obesity. Nutrition, 2015, 31(1), 51-57.
[http://dx.doi.org/10.1016/j.nut.2014.04.019] [PMID: 25441587]
[32]
Pechlaner, R.; Weiss, G.; Bansal, S.; Mayr, M.; Santer, P.; Pallhuber, B.; Notdurfter, M.; Bonora, E.; Willeit, J.; Kiechl, S. Inadequate hepcidin serum concentrations predict incident type 2 diabetes mellitus. Diabetes Metab. Res. Rev., 2016, 32(2), 187-192.
[http://dx.doi.org/10.1002/dmrr.2711] [PMID: 26378394]
[33]
Guo, X.; Zhou, D.; An, P.; Wu, Q.; Wang, H.; Wu, A.; Mu, M.; Zhang, D.; Zhang, Z.; Wang, H.; He, L.; Liu, Y.; Wang, F. Associations between serum hepcidin, ferritin and Hb concentrations and type 2 diabetes risks in a Han Chinese population. Br. J. Nutr., 2013, 110(12), 2180-2185.
[http://dx.doi.org/10.1017/S0007114513001827] [PMID: 23742704]

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