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Clinical Research in Urology  •  Vol 3  •  Issue 1  •  2020 22
INTRODUCTION
D
iabetes poses a serious health risk among elderly
individuals.[1]
It is a disease that is associated with a
deficiency of insulin or its impairment. It is a known
fact that the pancreas releases insulin to aid the body store
and use sugar and fat from the food. Diabetes can result
when insulin is reduced or lacking or when the body does not
respond actively to insulin.[2]
Some studies identified an essential regulatory agent called
hepcidin, which acts as a major regulator of systemic iron
metabolism.[3]
It is a small peptide with antimicrobial
properties which affects systemic iron availability. It is
mainly generated by liver sinusoidal endothelial cells in
response to iron-load. The hepcidin molecule participates
in parts in innate immunity and iron metabolism and can
be isolated from individual blood and urine;[4]
actually,
reversible diabetes conditions consist of prediabetes and
gestational diabetes. Prediabetes results when the blood
glucose levels are increased than normal but not too high to
be classified as diabetes. Prediabetes is mainly the precursor
of diabetes unless appropriate measures are taken to prevent
progression. Gestational diabetes results during pregnancy
but may resolve after the baby is delivered.[5]
The extrahepatic generation of hepcidin occurs gradually
and rarely at these sites it acts as an antimicrobial peptide. In
the kidney, hepcidin modulates the defense barriers against
urinary tract infections.[6]
Some researchers determined the important role of
interleukins (ILs) play in the human system. IL is a group
of cytokines with complex immunomodulatory functions
consisting of cell proliferation, maturation, migration, and
adhesion, which contributes in immune cell differentiation
and activation.[7]
This type of cytokine called IL-6 is an endogenous chemical
which is sensitive in inflammation and in B cell maturation.
Apart from being an immune protein, it is equally a pyrogen,
which contributes to fever in autoimmune, infectious, or
non-infectious disease. It is produced in the body, wherever
there is inflammation, either acute or chronic. This includes
situations such as trauma, burns, cancers, and infection. It
ORIGINAL ARTICLE
Alterations of Hepcidin and Interleukin in Diabetics
Johnkennedy Nnodim1
, Nwaokoro Joakin Chidozie2
, Nwanguma Eberechi1
,
Bako Hauwa3
, Ohalete Chinyere3
, Njoku-Obi Treasure4
1
Department of Medical Laboratory Science, Faculty of Health Science, Imo State University, Owerri, Nigeria,
2
Department of Public Health, Federal University of Technology, Owerri, Nigeria, 3
Department of Medical
Laboratory Science, College of Medical Sciences Ahmadu Bello University, Zaria Kaduna State, Nigeria,
4
Department of Microbiology, Faculty of Sciences, Imo State University, Owerri, Nigeria
ABSTRACT
Aim:Thisstudywasdonetodeterminethelevelsofhepcidinandinterleukin-6(IL-6)indiabetics.Materials and Methods: The
study involved 100 diabetics and 100 apparently normal subjects of the same age group 40–70. The levels of hepcidin
and IL-6 were measured with an enzyme-linked immunosorbent assay method. Results: The level of hepcidin and IL-6
significantly increased in the diabetics when compared to the controls (P  0.05). Conclusion: This study probably indicated
a significant increase in serum IL-6 and hepcidin levels in patients with diabetics.
Key words: Diabetics, interleukin-6, hepcidin
Address for correspondence:
Dr. Johnkennedy Nnodim, Department of Medical Laboratory Science, Faculty of Health Science, Imo State University,
Owerri, Nigeria. Tel.: +2348034237000
https://doi.org/10.33309/2638-7670.030105 www.asclepiusopen.com
© 2020 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.
Nnodim, et al.: Hepcidin and interleukin in diabetics
2 Clinical Research in Urology  •  Vol 3  •  Issue 1  •  2020
interacts with IL-6 receptor alpha to induce transcription of
inflammatory gene products.[8]
IL-6isimplicatedinahostofchronicdiseaseconditionslinked
with inflammation. IL-6 tends to lead higher susceptibility to
diabetes mellitus, as well as the systemic form of juvenile
rheumatoid arthritis.[9]
Hence, IL-6 participates in the short-term defense against
infection or damage. It equally warns the immune system
against the origin of inflammation. The disorder of this
regulation of molecule leads to disease.[10]
IL-6 insufficiency has a great response on immune activation
and IgA antibodies. Besides, IL-6 overexpression has clear,
effectiveresponses.Itregulatescellgrowthanddifferentiation
of various tissues.[11]
In this study, assessment of the hepcidin and IL-6 in diabetic
patients to provide further information for better management
MATERIALS AND METHODS
Subjects
This study included 100 confirmed diabetics. Age of the
participantsrangedfrom40to70years.Therewere50malesand
50 females. One hundred apparently healthy subjects matched
with the age and the sex matched were chosen as controls.
This study was conducted in accordance with the guidelines
approved by the Ethics Committee of the hospital. Informed
consent was also obtained from all the study participants.
Specimen collection and evaluation
Five milliliters of blood sample were collected by standard
venipuncture method from each participant and were
dispensed into the dry bottle. This was centrifuged to get the
serum for the analysis of the hepcidin and IL-6. Informed
consent of the participants was obtained.
Biochemical assay
The serum hepcidin and IL-6 were determined by the enzyme
link immunosorbent method.[12]
Statistical analysis
Student’s t-test for independent samples was used to compare
different study groups. All data were designated in terms
of mean  ±  standard deviation (SD). A value 0.05 was
considered to be statistically significant for this study. All
the statistical calculations were done using the computer
program Statistical Package for the Social Science (SPSS);
SPSS Inc., Chicago, IL, USA).
RESULTS
The results from Table 1 showed that the levels of hepcidin
and interleukin-6 were significantly increased in diabetes
when compared with the non-diabetes at P  0.05.
DISCUSSION
In the present study, the serum hepcidin was observed to
have significant increases in diabetics’ patients than healthy
controls. This is in line with other studies.[13]
This increase in
hepcidin among diabetic patients can be linked to oxidative
stress.[14]
Furthermore, a high statistically significant difference has
been observed in the level of IL-6 in diabetics when compared
with the controls. This was in line with the earlier studies
in which immunological cells such as macrophages and
T-lymphocytes release more pro-inflammatory cytokines,
particularly IL-6, which later lead to the generation of
hepcidin.[15]
This induction of hepcidin expression results in
hypoferremia, which accompanied inflammatory. Elevated
hepcidin generation stimulated by IL-6 enhances iron
retention in reticuloendothelial cells. Hence, weakening iron
release subsequently represses intestinal iron absorption.[16,17]
CONCLUSION
This study probably has shown the necessity of determining
the levels of hepcidin and IL-6 in diabetes, which tend to
maintain overall iron homeostasis in the body. This may lead
to a better outcome in the management of diabetics.
REFERENCES
1.	 Ripsin CM, Kang H, Urban RJ. Management of blood glucose
in Type 2 diabetes mellitus. Am Fam Physician 2009;79:29-36.
2.	 Kenny C. When hypoglycemia is not obvious: Diagnosing
and treating under-recognized and undisclosed hypoglycemia.
Prim Care Diabetes 2014;8:3-11.
3.	 MacIsaac RJ, Jerums G, Ekinci, EI. Glycemic control as
primary prevention for diabetic kidney disease. Adv Chronic
Kidney Dis 2018;25:141-8.
4.	 Ganz T. Hepcidin, a key regulator of iron metabolism and
mediator of anemia of inflammation. Blood 2003;102:783-8.
5.	 Valore EV, Ganz T. Posttranslational processing of hepcidin in
human hepatocytes is mediated by the prohormone convertase
furin. Blood Cells Mol Dis 2008;40:132-8.
6.	 Galushko EA. The clinical significance of hepcidin detection
Table 1: Mean value of hepcidin and interleukin-6 in
diabetics and non-diabetics
Biochemical parameters Diabetics Non-diabetics
Hepcidin (ng/ml) 6.50±1.99* 1.34±0.92
IL-6 (ng/ml) 163±3.95* 28.00±12.11
*Significantly decreased when compared with non-diabetics at
P0.05
Nnodim, et al.: Hepcidin and interleukin in diabetics
Clinical Research in Urology  •  Vol 3  •  Issue 1  •  2020 24
in the patients with anemia and rheumatoid arthritis. Klin Med
(Mosk) 2014;92:21-7.
7.	 Angelo GD. Role of hepcidin in the pathophysiology and
diagnosis of anemia. Blood Res 2013;48:10-5.
8.	 YacoubMF,FerwizHF,SaidF.Effectofinterleukinandhepcidin
in anemia of chronic diseases. Anemia 2020;2020:3041738.
9.	 den Elzen WP, de Craen AJ, Wiegerinck ET, Westendorp RG,
Swinkels DW, Gussekloo J. Plasma hepcidin levels and
anemia in old age. The Leiden 85-plus study. Haematologica
2013;98:448-54.
10.	 Ali ET, Jabbar AS, Mohammed AL. A comparative study of
interleukin 6, inflammatory markers, ferritin, and hematological
profile in rheumatoid arthritis patients with anemia of chronic
diseaseandirondeficiencyanemia.Anemia2019;2019:3457347.
11.	 Kulaksiz H, Fein E, Redecker P, Stremmel W, Adler G,
Cetin Y. Pancreatic beta-cells express hepcidin, an iron-uptake
regulatory peptide. J Endocrinol 2008;197:241-9.
12.	 Franchini M, Montagnana M, Lippi G. Hepcidin and iron
metabolism: From laboratory to clinical implications. Clin
Chim Acta 2010;411:1565-9.
13.	 Alex A, Sari V, Jyrki KV, Adeola A, Tomi-Pekka T. Serum
hepcidin concentrations and Type 2 diabetes. World J Diabetes
2015;6:978-82.
14.	 Singh B, Arora S, Agrawal P, Gupta SK. Hepcidin: A novel
peptide hormone regulating iron metabolism. Clin Chim Acta
2011;412:823-30.
15.	 Kulaksiz H, Theilig F, Bachmann S, Gehrke SG, Rost D,
JanetzkoA,etal.Theiron-regulatorypeptidehormonehepcidin:
Expression and cellular localization in the mammalian kidney.
J Endocrinol 2005;184:361-70.
16.	 Kell DB. Iron behaving badly: Inappropriate iron chelation
as a major contributor to the aetiology of vascular and other
progressive inflammatory and degenerative diseases. BMC
Med Genomics 2009;2:2.
17.	 Sow FB, Florence WC, Satoskar AR, Schlesinger LS,
Zwilling BS, Lafuse WP. Expression and localization of
hepcidin in macrophages: A role in host defense against
tuberculosis. J Leukoc Biol 2007;82:934-45.
How to cite this article: Nnodimy J, Chidozie NJ,
Eberechi N, Hauwa B, Chinyere O,Treasure N.Alterations
of Hepcidin and Interleukin in Diabetics. Clinic Res Urol
2020;3(1):22-24.

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Alterations of Hepcidin and Interleukin in Diabetics

  • 1. Clinical Research in Urology  •  Vol 3  •  Issue 1  •  2020 22 INTRODUCTION D iabetes poses a serious health risk among elderly individuals.[1] It is a disease that is associated with a deficiency of insulin or its impairment. It is a known fact that the pancreas releases insulin to aid the body store and use sugar and fat from the food. Diabetes can result when insulin is reduced or lacking or when the body does not respond actively to insulin.[2] Some studies identified an essential regulatory agent called hepcidin, which acts as a major regulator of systemic iron metabolism.[3] It is a small peptide with antimicrobial properties which affects systemic iron availability. It is mainly generated by liver sinusoidal endothelial cells in response to iron-load. The hepcidin molecule participates in parts in innate immunity and iron metabolism and can be isolated from individual blood and urine;[4] actually, reversible diabetes conditions consist of prediabetes and gestational diabetes. Prediabetes results when the blood glucose levels are increased than normal but not too high to be classified as diabetes. Prediabetes is mainly the precursor of diabetes unless appropriate measures are taken to prevent progression. Gestational diabetes results during pregnancy but may resolve after the baby is delivered.[5] The extrahepatic generation of hepcidin occurs gradually and rarely at these sites it acts as an antimicrobial peptide. In the kidney, hepcidin modulates the defense barriers against urinary tract infections.[6] Some researchers determined the important role of interleukins (ILs) play in the human system. IL is a group of cytokines with complex immunomodulatory functions consisting of cell proliferation, maturation, migration, and adhesion, which contributes in immune cell differentiation and activation.[7] This type of cytokine called IL-6 is an endogenous chemical which is sensitive in inflammation and in B cell maturation. Apart from being an immune protein, it is equally a pyrogen, which contributes to fever in autoimmune, infectious, or non-infectious disease. It is produced in the body, wherever there is inflammation, either acute or chronic. This includes situations such as trauma, burns, cancers, and infection. It ORIGINAL ARTICLE Alterations of Hepcidin and Interleukin in Diabetics Johnkennedy Nnodim1 , Nwaokoro Joakin Chidozie2 , Nwanguma Eberechi1 , Bako Hauwa3 , Ohalete Chinyere3 , Njoku-Obi Treasure4 1 Department of Medical Laboratory Science, Faculty of Health Science, Imo State University, Owerri, Nigeria, 2 Department of Public Health, Federal University of Technology, Owerri, Nigeria, 3 Department of Medical Laboratory Science, College of Medical Sciences Ahmadu Bello University, Zaria Kaduna State, Nigeria, 4 Department of Microbiology, Faculty of Sciences, Imo State University, Owerri, Nigeria ABSTRACT Aim:Thisstudywasdonetodeterminethelevelsofhepcidinandinterleukin-6(IL-6)indiabetics.Materials and Methods: The study involved 100 diabetics and 100 apparently normal subjects of the same age group 40–70. The levels of hepcidin and IL-6 were measured with an enzyme-linked immunosorbent assay method. Results: The level of hepcidin and IL-6 significantly increased in the diabetics when compared to the controls (P 0.05). Conclusion: This study probably indicated a significant increase in serum IL-6 and hepcidin levels in patients with diabetics. Key words: Diabetics, interleukin-6, hepcidin Address for correspondence: Dr. Johnkennedy Nnodim, Department of Medical Laboratory Science, Faculty of Health Science, Imo State University, Owerri, Nigeria. Tel.: +2348034237000 https://doi.org/10.33309/2638-7670.030105 www.asclepiusopen.com © 2020 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.
  • 2. Nnodim, et al.: Hepcidin and interleukin in diabetics 2 Clinical Research in Urology  •  Vol 3  •  Issue 1  •  2020 interacts with IL-6 receptor alpha to induce transcription of inflammatory gene products.[8] IL-6isimplicatedinahostofchronicdiseaseconditionslinked with inflammation. IL-6 tends to lead higher susceptibility to diabetes mellitus, as well as the systemic form of juvenile rheumatoid arthritis.[9] Hence, IL-6 participates in the short-term defense against infection or damage. It equally warns the immune system against the origin of inflammation. The disorder of this regulation of molecule leads to disease.[10] IL-6 insufficiency has a great response on immune activation and IgA antibodies. Besides, IL-6 overexpression has clear, effectiveresponses.Itregulatescellgrowthanddifferentiation of various tissues.[11] In this study, assessment of the hepcidin and IL-6 in diabetic patients to provide further information for better management MATERIALS AND METHODS Subjects This study included 100 confirmed diabetics. Age of the participantsrangedfrom40to70years.Therewere50malesand 50 females. One hundred apparently healthy subjects matched with the age and the sex matched were chosen as controls. This study was conducted in accordance with the guidelines approved by the Ethics Committee of the hospital. Informed consent was also obtained from all the study participants. Specimen collection and evaluation Five milliliters of blood sample were collected by standard venipuncture method from each participant and were dispensed into the dry bottle. This was centrifuged to get the serum for the analysis of the hepcidin and IL-6. Informed consent of the participants was obtained. Biochemical assay The serum hepcidin and IL-6 were determined by the enzyme link immunosorbent method.[12] Statistical analysis Student’s t-test for independent samples was used to compare different study groups. All data were designated in terms of mean  ±  standard deviation (SD). A value 0.05 was considered to be statistically significant for this study. All the statistical calculations were done using the computer program Statistical Package for the Social Science (SPSS); SPSS Inc., Chicago, IL, USA). RESULTS The results from Table 1 showed that the levels of hepcidin and interleukin-6 were significantly increased in diabetes when compared with the non-diabetes at P 0.05. DISCUSSION In the present study, the serum hepcidin was observed to have significant increases in diabetics’ patients than healthy controls. This is in line with other studies.[13] This increase in hepcidin among diabetic patients can be linked to oxidative stress.[14] Furthermore, a high statistically significant difference has been observed in the level of IL-6 in diabetics when compared with the controls. This was in line with the earlier studies in which immunological cells such as macrophages and T-lymphocytes release more pro-inflammatory cytokines, particularly IL-6, which later lead to the generation of hepcidin.[15] This induction of hepcidin expression results in hypoferremia, which accompanied inflammatory. Elevated hepcidin generation stimulated by IL-6 enhances iron retention in reticuloendothelial cells. Hence, weakening iron release subsequently represses intestinal iron absorption.[16,17] CONCLUSION This study probably has shown the necessity of determining the levels of hepcidin and IL-6 in diabetes, which tend to maintain overall iron homeostasis in the body. This may lead to a better outcome in the management of diabetics. REFERENCES 1. Ripsin CM, Kang H, Urban RJ. Management of blood glucose in Type 2 diabetes mellitus. Am Fam Physician 2009;79:29-36. 2. Kenny C. When hypoglycemia is not obvious: Diagnosing and treating under-recognized and undisclosed hypoglycemia. Prim Care Diabetes 2014;8:3-11. 3. MacIsaac RJ, Jerums G, Ekinci, EI. Glycemic control as primary prevention for diabetic kidney disease. Adv Chronic Kidney Dis 2018;25:141-8. 4. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003;102:783-8. 5. Valore EV, Ganz T. Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin. Blood Cells Mol Dis 2008;40:132-8. 6. Galushko EA. The clinical significance of hepcidin detection Table 1: Mean value of hepcidin and interleukin-6 in diabetics and non-diabetics Biochemical parameters Diabetics Non-diabetics Hepcidin (ng/ml) 6.50±1.99* 1.34±0.92 IL-6 (ng/ml) 163±3.95* 28.00±12.11 *Significantly decreased when compared with non-diabetics at P0.05
  • 3. Nnodim, et al.: Hepcidin and interleukin in diabetics Clinical Research in Urology  •  Vol 3  •  Issue 1  •  2020 24 in the patients with anemia and rheumatoid arthritis. Klin Med (Mosk) 2014;92:21-7. 7. Angelo GD. Role of hepcidin in the pathophysiology and diagnosis of anemia. Blood Res 2013;48:10-5. 8. YacoubMF,FerwizHF,SaidF.Effectofinterleukinandhepcidin in anemia of chronic diseases. Anemia 2020;2020:3041738. 9. den Elzen WP, de Craen AJ, Wiegerinck ET, Westendorp RG, Swinkels DW, Gussekloo J. Plasma hepcidin levels and anemia in old age. The Leiden 85-plus study. Haematologica 2013;98:448-54. 10. Ali ET, Jabbar AS, Mohammed AL. A comparative study of interleukin 6, inflammatory markers, ferritin, and hematological profile in rheumatoid arthritis patients with anemia of chronic diseaseandirondeficiencyanemia.Anemia2019;2019:3457347. 11. Kulaksiz H, Fein E, Redecker P, Stremmel W, Adler G, Cetin Y. Pancreatic beta-cells express hepcidin, an iron-uptake regulatory peptide. J Endocrinol 2008;197:241-9. 12. Franchini M, Montagnana M, Lippi G. Hepcidin and iron metabolism: From laboratory to clinical implications. Clin Chim Acta 2010;411:1565-9. 13. Alex A, Sari V, Jyrki KV, Adeola A, Tomi-Pekka T. Serum hepcidin concentrations and Type 2 diabetes. World J Diabetes 2015;6:978-82. 14. Singh B, Arora S, Agrawal P, Gupta SK. Hepcidin: A novel peptide hormone regulating iron metabolism. Clin Chim Acta 2011;412:823-30. 15. Kulaksiz H, Theilig F, Bachmann S, Gehrke SG, Rost D, JanetzkoA,etal.Theiron-regulatorypeptidehormonehepcidin: Expression and cellular localization in the mammalian kidney. J Endocrinol 2005;184:361-70. 16. Kell DB. Iron behaving badly: Inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics 2009;2:2. 17. Sow FB, Florence WC, Satoskar AR, Schlesinger LS, Zwilling BS, Lafuse WP. Expression and localization of hepcidin in macrophages: A role in host defense against tuberculosis. J Leukoc Biol 2007;82:934-45. How to cite this article: Nnodimy J, Chidozie NJ, Eberechi N, Hauwa B, Chinyere O,Treasure N.Alterations of Hepcidin and Interleukin in Diabetics. Clinic Res Urol 2020;3(1):22-24.