The role of inflammation IL-6, TNF-α in type -2 Diabetes Mellitus
DOI:
https://doi.org/10.36320/ajb/v17.i2.19615Keywords:
diabetes mellitus, TNF-α, insulin resistance, β-cell, IL-6Abstract
Background: Diabetes mellitus is a broad term that refers to a group of metabolic disorders characterized by persistent hyperglycemia, The reason is either a disruption in insulin secretion, varying degrees of insulin resistance, or both. In type 2 diabetes, the pathways leading to β-cell death and malfunction are less clear, but the common denominator seems to be inadequate β-cell insulin production, which often occurs in the context of insulin resistance. An essential indicator of long-term glycemic control and an accurate biomarker for the diagnosis and prognosis of diabetes is HbA1c. The glycation process produces HbA1c, which is a byproduct of Amadori rearrangement and accumulates up in red blood cells. Tumor necrosis factor-alpha (TNF-α) is a cytokine implicated in systemic inflammation that is generated by activated macrophages, CD4+ lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, and neurons. It usually causes an acute phase response. TNF-α was the first proinflammatory cytokine identified as having a role in the etiology of insulin resistance and type 2 diabetes. T2DM patients have been discovered to have higher levels of circulating inflammatory markers such TNF-α and IL6.In patients with One of the most prevalent metabolic diseases in the world, type 2 diabetes mellitus as a long-term metabolic condition marked by high blood glucose levels that eventually damages the heart, blood vessels, eyes, kidneys, and nerves. T2DM, which accounts for more than 90% of cases of diabetes mellitus, is characterized by tissue insulin resistance (IR), insufficient compensatory insulin secretory response, and insufficient insulin secretion by pancreatic islet β-cells that cause it elevated risk for mortality, CVD and the advancement of type 2 diabetes mellitus.
Methods: For this research, 120 blood samples were collected from patients with DM type 2 and 60 volunteers. A sandwich ELISA was used to estimate the serum levels of human TNF-α, and IL-6 and the results were statistically processed in SPSS.
Results: Results: The study showed no significant difference (p>0.407) in the mean age among patient groups was (44.51±12.33) years, while the control group was (41.13±10.22) years. The study also examined body weight distribution, finding no significant difference(p->0.32) between patients (24.54±3.44) and the control group (25.11±3.21), serum IL-6 patient groups was (6.44±2.11) while the control group was (1.43±0.32) and TNF-α patient groups was (16.22±2.45) while the control group was (2.34±0.33) in type 2 diabetes mellitus patients compared to the healthy control group.
Conclusions: The disease known as T2DM is complex One of the most prevalent metabolic diseases in the world, type 2 diabetes mellitus as a long-term metabolic condition marked by high blood glucose levels association with increase inflammatory biomarkers that leads to developments CVD and kidney failure.
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References
1. Roden M, Shulman GI: The integrative biology of type 2 diabetes. Nature 2019, 576(7785):51-60.
2. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C: Pathophysiology of Type 2 Diabetes Mellitus. 2020, 21(17):6275.
3. Bellou V, Belbasis L, Tzoulaki I, Evangelou EJPo: Risk factors for type 2 diabetes mellitus: an exposure-wide umbrella review of meta-analyses. 2018, 13(3):e0194127.
4. Sinha R, Dufour S, Petersen KF, LeBon V, Enoksson S, Ma Y-Z, Savoye M, Rothman DL, Shulman GI, Caprio SJD: Assessment of skeletal muscle triglyceride content by 1H nuclear magnetic resonance spectroscopy in lean and obese adolescents: relationships to insulin sensitivity, total body fat, and central adiposity. 2002, 51(4):1022-1027.
5. Cerf MEJFie: Beta cell dysfunction and insulin resistance. 2013, 4:37.
6. Meur G, Anindya R, Rutter GA: Chapter 10 - Biochemistry and immunology of inflammation-mediated responses in the development of diabetes mellitus. In: Biochemical Immunology of Diabetes and Associated Complications. Edited by Tripathi P, Tripathi RP, Kaushik MP: Academic Press; 2024: 169-207.
7. Khin PP, Lee JH, Jun H-S: Pancreatic Beta-cell Dysfunction in Type 2 Diabetes. 2023, 21:1721727X231154152.
8. Serbis A, Giapros V, Tsamis K, Balomenou F, Galli-Tsinopoulou A, Siomou E: Beta Cell Dysfunction in Youth- and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients. 2023, 15(9):2217.
9. Saisho YJJocm: Importance of beta cell function for the treatment of type 2 diabetes. 2014, 3(3):923-943.
10. Artasensi A, Pedretti A, Vistoli G, Fumagalli L: Type 2 Diabetes Mellitus: A Review of Multi-Target Drugs. 2020, 25(8):1987.
11. Liu C, Li Q, Feng X, Zhu J, Li Q: Deterioration of diabetic nephropathy via stimulating secretion of cytokines by atrial natriuretic peptide. BMC Endocr Disord 2021, 21(1):204.
12. Hotamisligil GSJN: Inflammation and metabolic disorders. 2006, 444(7121):860-867.
13. Pickup JCJDc: Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. 2004, 27(3):813-823.
14. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PMJj: C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. 2001, 286(3):327-334.
15. Zand H, Morshedzadeh N, Naghashian FJD, Research MSC, Reviews: Signaling pathways linking inflammation to insulin resistance. 2017, 11:S307-S309.
16. Nieto-Vazquez I, Fernández-Veledo S, Krämer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo MJAop, biochemistry: Insulin resistance associated to obesity: the link TNF-alpha. 2008, 114(3):183-194.
17. Alzamil HJJoo: Elevated serum TNF‐α is related to obesity in type 2 diabetes mellitus and is associated with glycemic control and insulin resistance. 2020, 2020(1):5076858.
18. Fernández-Real JM, Ricart WJEr: Insulin resistance and chronic cardiovascular inflammatory syndrome. 2003, 24(3):278-301.
19. Wellen KE, Hotamisligil GSJTJoci: Inflammation, stress, and diabetes. 2005, 115(5):1111-1119.
20. Fadaei R, Bagheri N, Heidarian E, Nouri A, Hesari Z, Moradi N, Ahmadi A, Ahmadi R: Serum levels of IL-32 in patients with type 2 diabetes mellitus and its relationship with TNF-α and IL-6. Cytokine 2020, 125:154832.
21. Kado S, Nagase T, Nagata NJAd: Circulating levels of interleukin-6, its soluble receptor and interleukin-6/interleukin-6 receptor complexes in patients with type 2 diabetes mellitus. 1999, 36:67-72.
22. Souza JRM, Oliveira RT, Blotta MHS, Coelho ORJAbdc: Serum levels of interleukin-6 (Il-6), interleukin-18 (Il-18) and C-reactive protein (CRP) in patients with type-2 diabetes and acute coronary syndrome without ST-segment elevation. 2008, 90:94-99.
23. Su H, Lei CT, Zhang C: Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Frontiers in immunology 2017, 8:405.
24. Zheng M, Wang X, Guo H, Fan Y, Song Z, Lu Z, Wang J, Zheng C, Dong L, Ma YJJodr: The cytokine profiles and immune response are increased in COVID‐19 patients with type 2 diabetes mellitus. 2021, 2021(1):9526701.
25. Reddy VKK, Shiddapur G, Jagdale N, Kondapalli MP, Adapa S, Shiddapur GJC: Investigating Interleukin-6 Levels in Type 2 Diabetes Mellitus Patients With and Without Diabetic Nephropathy. 2024, 16(8).
26. Çelik SP, Parilti DN, Açik L, Yalçin MM, Yetkin İ, Yunusov E: NAMPT, IL-6, and vaspin gene expressions and serum protein levels in type 2 diabetes mellitus and related complication. Turkish journal of biology = Turk biyoloji dergisi 2024, 48(2):133-141.
27. Khdaer HM, Aldabagh MAH, Altai GA: FUNCTION ROLE OFIL-6-174 GENE POLYMORPHISMS IN ASSOCIATION WITH IL-6 LEVELS IN TYPE 2 DIABETES MELLITUS. Wiadomosci lekarskie (Warsaw, Poland : 1960) 2022, 75(3):659-663.
28. Mirza S, Hossain M, Mathews C, Martinez P, Pino P, Gay JL, Rentfro A, McCormick JB, Fisher-Hoch SP: Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: A cross-sectional study. Cytokine 2012, 57(1):136-142.
29. Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M: Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: A systematic review and meta-analysis. Cytokine 2016, 86:100-109.
30. Moller DE: Potential Role of TNF-α in the Pathogenesis of Insulin Resistance and Type 2 Diabetes. Trends in Endocrinology & Metabolism 2000, 11(6):212-217.
31. Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, García-Pérez J: Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nature reviews Nephrology 2011, 7(6):327-340.
32. Tangvarasittichai S, Pongthaisong S, Tangvarasittichai OJIJoCB: Tumor necrosis factor-Α, interleukin-6, C-reactive protein levels and insulin resistance associated with type 2 diabetes in abdominal obesity women. 2016, 31:68-74.
33. Pedersen M, Bruunsgaard H, Weis N, Hendel HW, Andreassen BU, Eldrup E, Dela F, Pedersen BK: Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mechanisms of Ageing and Development 2003, 124(4):495-502.
34. Wu W, Wang M, Sun Z, Wang X, Miao J, Zheng ZJAd: The predictive value of TNF-α and IL-6 and the incidence of macrovascular complications in patients with type 2 diabetes. 2012, 49:3-7.
35. Festa A, D'agostino Jr R, Howard G, Mykkänen L, Tracy RP, Haffner SMJKi: Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study. 2000, 58(4):1703-1710.
36. Pickup JC, Chusney GD, Thomas SM, Burt DJLs: Plasma interleukin-6, tumour necrosis factor α and blood cytokine production in type 2 diabetes. 2000, 67(3):291-300.
37. Festa A, D’Agostino Jr R, Howard G, Mykkänen L, Tracy RP, Haffner SMJC: Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). 2000, 102(1):42-47.
38. Arnalich F, Hernanz A, Lopez-Maderuelo D, Pena J, Camacho J, Madero R, Vazquez J, Montiel CJH, Research M: Enhanced acute-phase response and oxidative stress in older adults with type II diabetes. 2000, 32(10):407-412.
39. Reinehr T: Inflammatory markers in children and adolescents with type 2 diabetes mellitus. Clinica Chimica Acta 2019, 496:100-107.
40. Su X, He J, Cui J, Li H, Men J: The effects of aerobic exercise combined with resistance training on inflammatory factors and heart rate variability in middle-aged and elderly women with type 2 diabetes mellitus. Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc 2022, 27(6):e12996.
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