Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2024; 70(6): 9-16


FERRITIN IN THE BLOOD OF PATIENTS WITH TYPE 2 DIABETES AND DIABETIC RETINOPATHY: A MARKER OF INFLAMMATION OR ANEMIA?

L.V. Natrus1, V.S. Tsybulskyi2, V.M. Hanyuk1, Iu.O. Panchenko2,

  1. Bogomolets National medical university, Kyiv, Ukraine
  2. Shupyk National University of Health Care of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz70.06.009


Abstract

Measuring the ferritin content in the blood is the most informative test for detecting iron deficiency and is recommended by the protocols for the diagnosis of anemia. However, ferritin as a marker of acute and chronic inflammation is nonspecifically increased in various inflammatory conditions. Mechanisms reflecting the significant role of chronic low-intensity inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) are being actively studied. Our aim was to analyze the content of ferritin in the plasma of patients with different stages of diabetic retinopathy (DR) on the background of T2DM in comparison with hemogram indicators and inflammatory markers. Ferritin content in blood plasma was determined by enzyme immunoassay in 106 patients with non-proliferative DR, moderate and progressive proliferative DR. The patients showed an increase in ferritin content relative to the control group and a progressive increase with deepening of the stage of retinopathy. In the group of moderate proliferative DR, the indicator was higher than the control by 23%, and in the group of progressive proliferative DR by 26%. The difference in ferritin content was observed in patients depending on gender. In men, an increase in ferritin content was found by 1.6 times relative to the value in women, in groups of proliferative DR, the indicators differed by 1.1 and 1.3 times. Indicators of the number of erythrocytes and hemoglobin content in the blood of male patients had a tendency to decrease compared to similar indicators of healthy men. In patients with T2DM, the ferritin content was elevated regardless of the underlying anemic state, therefore, it cannot be used as a diagnostic test for iron deficiency. A significant two-way correlation of ferritin and interleukin-10 content was found (r = 0.235). No correlation was found with the index of interleukin-1b and non-neuronal enolase, which characterizes the content of ferritin in the blood of patients with DR on the background of T2DM as a marker of chronic inflammation.

Keywords: ferritin; erythrocytes; hemoglobin; proliferative; non-proliferative diabetic retinopathy; low intensity inflammation.

References

  1. Guillemin C, Plomteux G, Dezier JF, Paris M, Pressac M, Revenant MC, Vernet M. Valeurs de référence de la ferritine érythrocytaire chez l'enfant et l'adulte [Reference values of erythrocyte ferritin in children and adults]. Ann Biol Clin (Paris). 1989;47(4):203-6.
  2. Guyatt GH, Oxman AD, Ali M, Willan A, McIlroy W, Patterson C. Laboratory diagnosis of iron-deficiency anemia: an overview. J Gen Int Med. 1992;7:145-53. CrossRef PubMed
  3. Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: Past, present and future. Biochim Biophys Acta. 2010 Aug;1800(8):760-9. CrossRef PubMed PubMedCentral
  4. Zandman-Goddard G, Shoenfeld Y. Ferritin in autoimmune diseases. Autoimmun Rev. 2007;6:457-63. CrossRef PubMed
  5. Tran TN, Eubanks SK, Schaffer KJ, Zhou CY, Linder MC. Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron. Blood. 1997;90:4979-86. CrossRef PubMed
  6. Ruddell RG, Hoang-Le D, Barwood JM, Rutherford PS, Piva TJ, Watters DJ, Santambrogio P, Arosio P, Ramm GA. Ferritin functions as a proinflammatory cytokine via iron-independent protein kinase C zeta/nuclear factor kappaB-regulated signaling in rat hepatic stellate cells. Hepatology. 2009;49:887-900. CrossRef PubMed PubMedCentral
  7. Ganz T, Nemeth E. Iron sequestration and anemia of inflammation. Semin Hematol. 2009;46:387-93. CrossRef PubMed PubMedCentral
  8. Ganz T. Systemic iron homeostasis. Physiol Rev. 2013;93:1721-41. CrossRef
  9. Hintze KJ, Theil EC. Cellular regulation and molecular interactions of the ferritins. Cell Mol Life Sci. 2006;63:591-600. CrossRef PubMed PubMedCentral
  10. Sangkhae V, Nemeth E. Regulation of the iron homeostatic hormone hepcidin. Adv Nutr. 2017 Jan 17;8(1):126-36. CrossRef PubMed PubMedCentral
  11. Davis M, Fisher M, Gangnon R, et al. Risk factors for highrisk proliferative diabetic retinopathy and severe visual loss: Early treatment diabetic retinopathy study report
  12. Investigat Ophthalmol Vis Sci. 1998; 39: 233-52.
  13. Hanyuk V, Petrenko O, Natrus L, Prusak O. Morpho-functional and structural changes of erythrocytes of patients with proliferative diabetic retinopathy and different duration of type 2 diabetes mellitus. Oftalmol Zh. 2021; 5:21-7. CrossRef
  14. Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, Regan M, Weatherall D, Chou DP, Eisele TP, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123:615-24. CrossRef PubMed PubMedCentral
  15. Camaschella C. Iron-deficiency anemia. N Engl J Med 2015;372:1832-43. CrossRef PubMed
  16. Galaris D, Pantopoulos K. Oxidative stress and iron homeostasis: mechanistic and health aspects. Crit Rev Clin Lab Sci 2008;45:1-23. CrossRef PubMed
  17. Muriach M, Flores-Bellver M, Romero FJ, Barcia JM. Diabetes and the brain: oxidative stress, inflammation, and autophagy. Oxid Med Cell Long. 2014, 102158. CrossRef PubMed PubMedCentral
  18. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058-70. CrossRef PubMed PubMedCentral
  19. Mikheytseva IM. Current view on pathogenic mechanisms of diabetic retinopathy. Fiziol Zh. 202369(3): 106-4.
  20. Bianco L, Arrigo A, Aragona E, Antropoli A, Berni A, Saladino A, Battaglia Parodi M, Bandello F. Neuroinflammation and neurodegeneration in diabetic retinopathy. Front Aging Neurosci. 2022, Aug 16;14:937999. CrossRef PubMed PubMedCentral
  21. Esmaeili MH, Enayati M, Abkenar FK, Ebrahimian F, Salari A-A. Glibenclamide mitigates cognitive impairment and hippocampal neuroinflammation in rats with type 2 diabetes and sporadic Alzheimer-like disease. Behav Brain Res. 2020;379:112359. CrossRef PubMed
  22. Galicia-Garcia U, Benito-Vicente A, Jebari S, LarreaSebal A, Siddiqi H, Uribe KB, Ostolaza H, Martin C. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 2020;21(17):6275. CrossRef PubMed PubMedCentral
  23. Olefsky JM, Glass CK, et al. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219-46. CrossRef PubMed
  24. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011;121:2111-7. CrossRef PubMed PubMedCentral
  25. Nishimura S, Manabe I, Nagasaki M et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15:914-20. CrossRef PubMed
  26. Tsalamandris S, Antonopoulos AS, Oikonomou E, Papamikroulis GA, Vogiatzi G, Papaioannou S, Deftereos S, Tousoulis D. The role of inflammation in diabetes: Current concepts and future perspectives. Eur Cardiol. 2019 Apr;14(1):50-9. CrossRef PubMed PubMedCentral
  27. Panchenko IuO, Tsybulskyi VS, Natrus LV, Zakharevych GL. The level of neuroinflammatory markers in patients with diabetic retinopathy in the setting of type 2 diabetes mellitus and genetically determined hyperhomocysteinaemia. Oftalmolog Zh. 2024; 4:13-20.

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2025.