The Difference Levels of Hepcidin and Interleukin-6 between Obese and Non-Obese Type 2 Diabetes Mellitus

Mabruratussania Maherdika, Indranila Kustarini Samsuria, Meita Hendrianingtyas, Nyoman Suci Widyastiti, Muji Rahayu


BACKGROUND: Inflammation occurs in chronic diseases such as type 2 diabetes mellitus (DM). Insulin resistance and inflammation in type 2 DM with obesity can increase interleukin (IL)-6, causing an increase in hepcidin synthesis in the liver. Increased inflammation can exacerbate the course of type 2 DM. This study aims to prove that there are differences in the levels of hepcidin and IL-6 between obese and non-obese type 2 DM.

METHODS: This cross-sectional study was conducted on 61 patients with type 2 DM, consist of 22 male and 39 female with an age of more than 40 years. Type 2 DM subjects were obtained from a doctor's diagnosis and were divided into obese and non-obese groups based on body mass index (BMI). Hepcidin and IL-6 levels were examined using the Enzyme-Linked Immunosorbent Assay (ELISA) principle. The data were analyzed using an independent t-test and Mann-Whitney test.

RESULTS: The mean level of hepcidin in the obese with type 2 DM group was 25.32±11.54 ng/mL, and non-obese was 11.94±5.31 ng/mL. The median level of IL-6 in the obese with type 2 DM group was 11.9 (5-61) pg/mL, and non-obese 4.8 (1.5-9.8) pg/mL. There was a significant difference in hepcidin and IL-6 levels between the obese and non-obese groups (p=0.000).

CONCLUSION: Hepcidin and IL-6 levels in the obese group with type 2 DM were higher than non-obese group.

KEYWORDS: type 2 diabetes mellitus, obesity, hepcidin, interleukin-6

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Perkumpulan Endokrinologi Indonesia. Pedoman Pengelolaan Dan Pencegahan Diabetes Mellitus Tipe 2 Dewasa Di Indonesia 2021. Jakarta: Perkumpulan Endokrinologi Indonesia; 2021, article.

World Health Organization. Global Report on Diabetes. Geneva: World Health Organization; 2016, article.

Ganz ML, Wintfeld N, Li Q, Alas V, Langer J, Hammer M. The association of body mass index with the risk of type 2 diabetes: A case-control study nested in an electronic health records system in the United States. Diabetol Metab Syndr. 2014; 6(1): 50, CrossRef.

World Health Organization [Internet]. Obesity [cited 2020 Sep 3, 2022]. Available from:

Hsu WC, Araneta MRG, Kanaya AM, Chiang JL, Fujimoto W. BMI cut points to identify at-risk asian americans for type 2 diabetes screening. Diabetes Care. 2015; 38(1): 150–8, CrossRef.

Ambachew S, Biadgo B. Hepcidin in iron homeostasis: diagnostic and therapeutic implications in type 2 diabetes mellitus patients. Acta Haematol. 2018; 138(4): 183–93, CrossRef.

Andrews M, Arredondo M. Ferritin levels and hepcidin mRNA expression in peripheral mononuclear cells from anemic type 2 diabetic patients. Biol Trace Elem Res. 2012; 149(1): 1-4, CrossRef.

Kevin M. Korelasi kadar hepcidin serum dengan indeks massa tubuh dan lingkar pinggang [Undergraduate Thesis]. Semarang: Universitas Diponegoro; 2017.

Ndevahoma F, Mukesi M, Dludla P V, Nkambule BB, Nepolo EP, Nyambuya TM. Body weight and its influence on hepcidin levels in patients with type 2 diabetes: A systematic review and meta-analysis of clinical studies. Heliyon. 2021; 7(3): e06429, CrossRef.

Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014; 6(10): a016295, CrossRef.

Rehman K, Akash MSH, Liaqat A, Kamal S, Qadir MI, Rasul A. Role of interleukin-6 in development of insulin resistance and type 2 diabetes mellitus. Crit Rev Eukaryot Gene Expr. 2017; 27(3): 229–36, CrossRef.

Rehman K, Akash MSH. Mechanisms of inflammatory responses and development of insulin resistance: How are they interlinked? J Biomed Sci. 2016; 23(1): 87, CrossRef.

Tsalamandris S, Antonopoulos AS, Oikonomou E, Papamikroulis GA, Vogiatzi G, Papaioannou S, et al. The role of inflammation in diabetes: current concepts and future perspectives. Eur Cardiol. 2019; 14(1): 50–9, CrossRef.

Daryabor G, Atashzar MR, Kabelitz D, Meri S, Kalantar K. The effects of type 2 diabetes mellitus on organ metabolism and the immune system. Front Immunol. 2020; 11: 1582, CrossRef.

Mao X, Chen H, Tang J, Wang L, Shu T. Hepcidin links gluco-toxicity to pancreatic beta cell dysfunction by inhibiting Pdx-1 expression. J Endocrinol. 2017; 6(3): 121–8, CrossRef.

Kanazawa M, Yoshiike N, Osaka T, Numba Y, Zimmet P, Inoue S. Criteria and classification of obesity in Japan and Asia-Oceania. World Rev Nutr Diet. 2005; 94: 1–12, CrossRef.

Leeners B, Geary N, Tobler PN, Asarian L. Ovarian hormones and obesity. Hum Reprod Update. 2017; 23(3): 300–21, CrossRef.

Chandrasekaran A. Body mass index-is it reliable indicator of obesity? J Nutr Weight Loss. 2018; 3(1): 111, CrossRef.

Kalyani RR, Egan JM. Diabetes and altered glucose metabolism with aging. Endocrinol Metab Clin North Am. 2013; 42(2): 333–47, CrossRef.

Al-Goblan AS, Al-Alfi MA, Khan MZ. Mechanism linking diabetes mellitus and obesity. Diabetes, Metab Syndr Obes Targets Ther. 2014; 7: 587–91, CrossRef.

Yogita R, Potheineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis. 2018; 11(8): 215–25, CrossRef.

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): 51–7, CrossRef.

Aignera E, Feldera KT, Oberkoflera H, Hahnea P, Auera S, Soyala S, et al. Glucose acts as a regulator of serum iron by increasing serum hepcidin concentrations. J Nutr Biochem. 2013; 24(1): 112–7, CrossRef.

Aregbesola A, Voutilainen S, Virtanen J, Aregbesola A, Tuomainen T-P. Serum hepcidin concentrations and type 2 diabetes. World J Diabetes. 2015; 6(7): 978–82, CrossRef.

Meiliana A, Dewi NM, Wijaya A. Adipose tissue, inflammation (meta-inflammation) and obesity management. Indones Biomed J. 2015; 7(3): 129–46, CrossRef.

Lina Y, Lawrence GS, Wijaya A. Association of free fatty acid (FFA), fatty acid binding protein (FABP) and adiponectin with tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) among obese non diabetic males. Indones Biomed J. 2009; 1(2): 31-7, CrossRef.

Tussing-Humphreys LM, Nemeth E, Fantuzzi G, Freels S, Guzman G, Holterman AXL, et al. Elevated systemic hepcidin and iron depletion in obese premenopausal females. Obesity. 2010; 18(7): 1449–56, CrossRef.

Ahmed AA. The significance of serum hepcidin on iron status in overweight and obese patients with iron-deficiency anemia. Iraqi J Hematol. 2020; 9(1): 30–3, CrossRef.

Laishram V, Debnath S, Hijam D, Das T, Saha S. Evaluation of serum interleukin 6 in type II diabetes mellitus. Int J Med Res Prof. 2017; 3(1): 156–60, CrossRef.

Susantiningsih T, Mustofa S. Ekspresi IL-6 dan TNF-α pada obesitas. J Kedokt UNILA. 2018; 2(2): 1956, article.

Bastard J-P, Maachi M, Lagathu C. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006; 17(1): 4–12, PMID.

Khaodhiar L, Ling PR, Blackburn GL, Bistrian BR. Serum levels of interleukin-6 and C-reactive protein correlate with body mass index across the broad range of obesity. J Parenter Enter Nutr. 2004; 28(6): 410–4, CrossRef.

Rodríguez-Mortera R, Caccavello R, Hermo R, Garay-Sevilla ME, Gugliucci, Alejandro. Higher hepcidin levels in adolescents with obesity are associated with metabolic syndrome dyslipidemia and visceral fat. Antioxidant. 2021; 10(5): 751, CrossRef.

Fillebeen C, Lam NH, Chow S, Botta A, Sweeney G, Pantopoulos, et al. Regulatory connections between iron and glucose metabolism. Int J Mol Sci. 2020; 21(20): 7773, CrossRef.

Vela D, Leshoski J, Gjorgievska ES, Hadzi-Petrushev N, Jakupaj M, Sopi RB, et al. The role of insulin therapy in correcting hepcidin levels in patients with type 2 diabetes mellitus. Oman Med J. 2017; 32(3): 195–200, CrossRef.


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