Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.7)
Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2015, vol. 24, nr 1, January-February, p. 69–78

doi: 10.17219/acem/38158

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Correlation of Hepcidin Level with Insulin Resistance and Endocrine Glands Function in Major Thalassemia

Hussein K. Al-Hakeim1,A,C,D,F, Manal M. Al-Khakani1,A,B,F, Mahmood A. Al-Kindi2,B,E,F

1 Department of Chemistry, College of Science, Kufa University, Iraq

2 Department of Internal Medicine, College of Medicine, Kufa University, Iraq

Abstract

Background. Hepcidin is a master regulator of iron metabolism that inhibits the transport of iron out of enterocytes and macrophages. Thalassemia major (TM) is associated with some of the endocrine disorders. However, studies have yet to be conducted on the correlation of hepcidin with hormone levels and insulin resistance (IR) in patients with TM.
Objectives. In the present study, the correlation of hepcidin level with some endocrine and biochemical parameters was investigated to determine the factors that mainly affect hepcidin correlation in patients with thalassemia. These factors include hormones, iron status, and IR parameters.
Material and Methods. Hepcidin and other measured biochemical parameters were compared between the TM patients (100) and healthy children (37).
Results. Serum thyroid-stimulating hormone (TSH) was positively correlated (p < 0.05) with hepcidin, iron, and ferritin. T4 hormone was correlated with ferritin only. Other hormones showed different correlation patterns with iron status parameters but were statistically insignificant (p > 0.05). The percentage of β-cell function was the only parameter among the IR parameters that showed a significant difference between thalassemic and control groups.
Conclusion. Thyroid and β-cells dysfunctions are common in TM patients with frequent blood transfusions. In addition, hepcidin and TSH levels can be predicted significantly using the most correlated factors with hepcidin. These factors, including ferritin, insulin and TSH were used to construct predicting equations: S. Hepcidin = = 0.003*Ferritin + 3.02*TSH + 0.12*Insulin + 16.85 (± 7.78) and TSH = 0.0083 × Insulin + 0.0042 × Ferritin + + 0.0937 × Hepcidin + 1.91 (± 1.373).

Key words

thalassemia, hepcidin, insulin resistance, hormones.

References (31)

  1. Hershko C: Pathogenesis and management of iron toxicity in thalassemia. Ann N Y Acad Sci 2010, 1202, 1–9.
  2. Li H, Rybicki AC, Suzuka SM, von Bonsdorff L, Breuer W, Hall CB, Cabantchik ZI: Transferrin therapy ameliorates disease in beta-thalassemic mice. Nat Med 2010, 16, 177–182.
  3. Gardenghi S, Ramos P, Marongiu MF, Melchiori L, Breda L, Guy E: Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice. J Clin Invest 2010, 120, 4466–4477.
  4. Parrow NL, Gardenghi S, Rivella S: Prospects for a hepcidin mimic to treat beta-thalassemia and hemochromatosis. Expert Rev Hematol 2011, 4, 233–235.
  5. Al-Samarrai AH, Adaay MH, Al-Tikriti KA, Al-Anzy MM: Evaluation of some essential element levels in thalassemia major patients in Mosul district, Iraq. Saudi Med J 2008, 29, 94–97.
  6. Abdulzahraa MS, Al-Hakeim HK, Ridha MM: Study of the effect of iron overload on the function of endocrine glands in male thalassemia patients: Asian J Trans Sci 2011, 5, 127–131.
  7. Walter PB, Macklin EA, Porter J, Evans P, Kwiatkowski JL, Neufeld EJ: Thalassemia Clinical Research Network Inflammation and oxidant-stress in beta-thalassemia patients treated with iron chelators deferasirox (ICL670) or deferoxamine: an ancillary study of the Novartis CICL670A0107 trial. Haematologica 2008, 93, 817–825.
  8. Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC: Survival and complications in patients with thalassemia major treated with transfusion and deferoxaamine. Haematologica 2004, 89, 1187–1193.
  9. Piperno A, Mariani R, Trombini P, Girelli D: Hepcidin modulation in human diseases: from research to clinic. World J Gastroenterol 2009, 15, 538–551.
  10. Layden BT, Durai V, Lowe Jr WL: G-Protein-Coupled Receptors, Pancreatic Islets, and Diabetes. Nature Education 2010, 3, 13.
  11. Kennedy A, Kohn M, Lammi A, Clarke S: Iron status and haematological changes in adolescent female inpatients with anorexia nervosa. J Paediatr Child Health 2004, 40, 430–432.
  12. Al-Bayatti AA: Insulin resistance and upper-body obesity in polycystic ovary syndrome Middle East Fertility Society Journal 2006, 11, 202–209.
  13. Hall JI, Vora N, Langworthy R, Stock S, Momin A, Sherwood RA: Leptin/adiponectin ratio in patients with coronary heart disease: comparing subjects with and without metabolic syndrome. Ann Clin Biochem 2011, 48, 327–331.
  14. Larade K, Storey KB: Accumulation and translation of ferritin heavy chain transcripts following anoxia exposure in a marine invertebrate. J Exp Biol 2004, 207, 1353–1360.
  15. Wu EX, Kim D, Tosti CL, Tang H, Jensen JH, Cheung JS: Magnetic resonance assessment of iron overload by separate measurement of tissue ferritin and hemosiderin iron. Ann N Y Acad Sci 2010, 1202, 115–122.
  16. Shizukuda Y, Bolan C, Nguyen T, Botello G, Tripodi D, Yau Y: Oxidative stress in asymptomatic subjects with hereditary hemochromatosis. Am J Hematol 2007, 82, 249–250.
  17. Galanello R, Agus A, Campus S, Danjou F, Giardina PJ, Grady RW: Combined iron chelation therapy. Ann NY Acad Sci 2010, 1202, 79–86.
  18. Lekawanvijit S, Chattipakorn N: Iron overload thalassemic cardiomyopathy: Iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol 2009, 25, 213–218.
  19. Casanovas G, Swinkels DW, Altamura S, Schwarz K, Laarakkers CM, Gross HJ, Wiesneth M: Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II. J Mol Med (Berl) 2011, 89, 811–816.
  20. Verga Falzacappa MV, Spasic MV, Kessler R, Stolte J, Hentze MW, Muckenthaler MU: STAT-3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood 2007, 109, 353–358.
  21. Kroot JJ, Tjalsma H, Fleming RE, Swinkels DW: Hepcidin in human iron disorders: diagnostic implications. Clin Chem 2011, 57, 1650–1669.
  22. Rund D, Rachmilewitz E: Medical progress, β-Thalassemia. N Engl J Med 2005, 353, 1135–1146.
  23. Voskaridou E, Anagnostopoulos A, Konstantopoulos K, Stoupa E, Spyropoulou E, Kiamouris C: Zoledronic acid for the treatment of osteoporosis in patients with beta-thalassemia: results from a single-center, randomized, placebo-controlled trial. Haematologica 2006, 91, 1193–1202.
  24. Mohammadian S, Bazrafshan HR, Sadeghi-Nejad A: Endocrine gland abnormalities in thalassemia major: a brief review. J Pediatr Endocrinol Metab 2003, 16, 957–964.
  25. Hamrahian AH, Oseni TS, Arafah BM: Measurements of serum free cortisol in critically ill patients. N Engl J Med 2004, 350, 1629–1638.
  26. Delvecchio M, Cavallo L: Growth and endocrine function in thalassemia major in childhood and adolescence. J Endocrinol Invest 2010, 33, 61–68.
  27. Cook JD, Flowers CH, Skikne BS: The quantitative assessment of body iron. Blood 2003, 101, 3359–3364.
  28. Gardenghi S, Marongiu MF, Ramos P, Guy E, Breda L, Chadburn A, Liu Y: Ineffective erythropoiesis in betathalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood 2007, 109, 5027–5035.
  29. Rivella S: Ineffective erythropoiesis and thalassemias. Cur Opin Hematol 2009, 16, 187–194.
  30. Filosa A, Di Maio S, Aloj G, Acampora C: Longitudinal study on thyroid function in patients with thalassemia major. J Pediatr Endocrinol Metab 2006, 19, 1397–1404.
  31. Toumba M, Sergis A, Kanaris C, Skordis N: Endocrine complications in patients with Thalassaemia Major. Pediatr Endocrinol Rev 2007, 5, 642–648.
© Wroclaw Medical University