Cytokines in the blood of patients with type 2 diabetes mellitus depending on the level of overweight/obesity (literature review and own data)

Authors

  • K.P. Zak State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • V.V. Popova State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0002-4116-0671
  • V.L. Orlenko State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0002-8400-576X
  • O.V. Furmanova State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • N.D. Tronko State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0001-7421-0981

DOI:

https://doi.org/10.22141/2224-0721.17.7.2021.244969

Keywords:

type 2 diabetes mellitus, immunity, cytokines, COVID-19

Abstract

The paper analyzes the current literature data and the results of our own researches concerning the state of the cytokine network: pro- and anti-inflammatory cytokines (interleukin (IL) 1α, IL-1β, IL-4, IL-6, IL-10, IL-17 and tumor necrosis factor (TNF) α), α- and β-chemokines, including IL-8 and IL-16, as well as adipokines (leptin and adiponectin) in the peripheral blood of patients with type 2 diabetes (T2D) with normal and increased body weight/obesity. It has been shown that patients with T2D are cha­racterized by an increased content of proinflammatory cytokines (IL-1, IL-6, IL-17, TNFα), α- and β-chemokines in the peripheral blood, including IL-8 and IL-16, as well as leptin with a decrease in adiponectin content. In lean patients (with body mass index (BMI) < 25.5 kg/m2) compared to lean normoglycemic individuals from the control group (BMI < 25.5 kg/m2), there is a small but significant increase in IL-1β, IL-6, IL-17, TNFα and leptin, which, as BMI increases, significantly increases in severe obesity (BMI > 30.0 kg/m2), especially in obese women (BMI > 35.0 kg/m2). Similarly, an increase in proinflammatory cytokines is observed in normoglycemic people, but not as signifi­cant as in T2D. Less clear data were obtained when during determination of the anti-inflammatory cytokines IL-4 and IL-10, which is explained by a significant polymorphism of their genes, and both protective and compensatory effects on pro-inflammatory cytokine rise. In T2D patients, especially those with obesity, there is an increase in the leptin level and a decrease in the adiponectin content. The severity of the course and the percentage of mortality are closely associated with the BMI of patients. The effectiveness of the fight against an increase in the incidence of T2D should be primarily aimed at preventing obesity, and in case of already developed T2D — at reducing concomitant obesity. The analysis of the data presented also suggests that a sharp increase in the content of pro-inflammatory cytokines (so called cytokine storm) observed in patients with T2D and obesity infected with COVID-19, is a consequence of the summation and potentiation of already existing inflammatory process.

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References

Paul WE, editor. Fundamental Immunology. 4th ed. Philadelphia: Lippincott-Raven; 1998. 1589 p.

Vozianov AF, Butenko AK, Zak KP. Tsitokiny. Biologicheskie i protivoopukholevye svoistva [Cytokines. Biological and antitumor properties]. Kyiv: Naukova dumka; 1998. 320 p. (in Russian).

Zak KP, Tron'ko ND, Popova VV, Butenko AK. Sakharnyi diabet. Immunitet. Tsitokiny [Diabetes. Immunity. Cytokines]. Kyiv: Knyga pljus; 2015. 485 p. (in Russian).

Tronko MD, Zak KP. Current advances in clinical pathophysiology in the study of the pathogenesis of type 1 and type 2 diabetes mellitus in humans. Mìžnarodnij endokrinologìčnij žurnal. 2019;15(6):422-434. doi:10.22141/ 2224-0721.15.6.2019.185403. (in Russian).

O'Shea JJ, Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science. 2010 Feb 26;327(5969):1098-1102. doi:10.1126/science.1178334.

Sabat IE, Lindsey AP, Membere A, et al. Invisible disabilities: unique strategies for workplace allies. Industrial and Organizational Psychology. 2014 Jun;7(2):259-265. doi:10.1111/iops.12145.

Zak KP, Gruzov MI, Khomenko BM, Shlyakhovenko VS. Ultrastructure of large granule-containing lymphocytes of human blood. Reports of the National Academy of Sciences of Ukraine. 1983;(4):73-77. (in Russian).

Hedjazifar S, Khatib Shahidi R, Hammarstedt A, et al. The Novel Adipokine Gremlin 1 Antagonizes Insulin Action and Is Increased in Type 2 Diabetes and NAFLD/NASH. Diabetes. 2020 Mar;69(3):331-341. doi:10.2337/db19-0701.

Kondratska I, Melnichenko S, Mankovsky B, Zak K. Serum interleukin-16 levels in patients with metabolic syndrome and diabetes mellitus. J Clin Lipidology. 2008;2(5 Suppl 1):S104. doi:10.1016/j.jacl.2008.08.227.

Mello VDF, Kolehmainen M, Schwab U, et al. Weight reduction decreases TNF-α and increases IL-6 gene expression in lymphocytes in subjects with metabolic syndrome - the GENOBIN study. In: 42nd EASD Annual Meeting of the European Association for the Study of Diabetes. 2006, September 14-17; Copenhagen, Denmark. Diabetologia. 2006;49(Suppl 1):466. doi:10.1007/s00125-006-0358-5.

Zhang Z, Yuan W, Sun L, et al. 1,25-Dihydroxyvitamin D3 targeting of NF-kappaB suppresses high glucose-induced MCP-1 expression in mesangial cells. Kidney Int. 2007 Jul;72(2):193-201. doi:10.1038/sj.ki.5002296.

Badr E, Assar M, Elshayeb EI, Fath El-Bab S, El-Kousy S. A preliminary study of the relation between IL-4 and hypertension in type II diabetes mellitus. Mol Biol Rep. 2018 Dec;45(6):1967-1972. doi:10.1007/s11033-018-4349-7.

Rodrigues KF, Pietrani NT, Bosco AA, Campos FMF, Sandrim VC, Gomes KB. IL-6, TNF-α, and IL-10 levels/polymorphisms and their association with type 2 diabetes mellitus and obesity in Brazilian individuals. Arch Endocrinol Metab. 2017 Sept-Oct;61(5):438-446. doi:10.1590/2359-3997000000254.

Williams A, Greene N, Kimbro K. Increased circulating cytokine levels in African American women with obesity and elevated HbA1c. Cytokine. 2020 Apr;128:154989. doi:10.1016/j.cyto.2020.154989.

International Diabetes Federation (IDF). IDF Diabetes Atlas. 9th ed. Brussels, Belgium: IDF; 2019. 176 p.

Bommer C, Sagalova V, Heesemann E, et al. Global Economic Burden of Diabetes in Adults: Projections From 2015 to 2030. Diabetes Care. 2018 May;41(5):963-970. doi:10.2337/dc17-1962.

Donath MY. Multiple benefits of targeting inflammation in the treatment of type 2 diabetes. Diabetologia. 2016 Apr;59(4):679-682. doi:10.1007/s00125-016-3873-z.

Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011 Feb;11(2):98-107. doi:10.1038/nri2925.

Netea MG, Balkwill F, Chonchol M, et al. A guiding map for inflammation. Nat Immunol. 2017 Jul 19;18(8):826-831. doi:10.1038/ni.3790.

Duncan BB, Schmidt MI, Pankow JS, et al. Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes. 2003 Jul;52(7):1799-1805. doi:10.2337/diabetes.52.7.1799.

Hu FB, Meigs JB, Li TY, Rifai N, Manson JE. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004 Mar;53(3):693-700. doi:10.2337/diabetes.53.3.693.

Furmanova OV, Zak KP, Popova VV, Tronko MD. Blood leukocyte composition and neutrophil to lymphocyte ratio in patients with newly diagnosed type 2 diabetes mellitus depending on the degree of overweight/obesity. Mìžnarodnij endokrinologìčnij žurnal. 2020;16(7):526-533. doi:10.22141/2224-0721.16.7.2020.219006. (in Russian).

Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A. Inflammatory process in type 2 diabetes: The role of cytokines. Ann N Y Acad Sci. 2006 Nov;1084:89-117. doi:10.1196/annals.1372.039.

Dinarello CA, Donath MY, Mandrup-Poulsen T. Role of IL-1beta in type 2 diabetes. Curr Opin Endocrinol Diabetes Obes. 2010 Aug;17(4):314-321. doi:10.1097/MED.0b013e32833bf6dc.

Mirza S, Hossain M, Mathews C, et al. 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 Jan;57(1):136-142. doi:10.1016/j.cyto.2011.09.029.

Donath MY, Dalmas É, Sauter NS, Böni-Schnetzler M. Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity. Cell Metab. 2013 Jun 4;17(6):860-872. doi:10.1016/j.cmet.2013.05.001.

Guarino D, Antonioli L, Fornai M, et al. Diabetes, obesity and inflammation: Persistence of elevated IL-1b after bariatric surgery. In: 53rd EASD Annual Meeting of the European Association for the Study of Diabetes. 2017, September 11-15; Lisbon, Portugal. Diabetologia. 2017;60(Suppl 1):1-97. doi:10.1007/s00125-017-4350-z.

Herder C, Zierer A, Koenig W, Roden M, Meisinger C, Thorand B. Transforming growth factor-beta1 and incident type 2 diabetes: results from the MONICA/KORA case-cohort study, 1984-2002. Diabetes Care. 2009 Oct;32(10):1921-1923. doi:10.2337/dc09-0476.

Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007 Apr 12;356(15):1517-1526. doi:10.1056/NEJMoa065213.

Mandrup-Poulsen T. Interleukin-1 antagonism: a sturdy companion for immune tolerance induction in type 1 diabetes? Diabetes. 2014 Jun;63(6):1833-1835. doi:10.2337/db14-0371.

Pham MN, Hawa MI, Pfleger C, et al. Pro- and anti-inflammatory cytokines in latent autoimmune diabetes in adults, type 1 and type 2 diabetes patients: Action LADA 4. Diabetologia. 2011 Jul;54(7):1630-1638. doi:10.1007/s00125-011-2088-6.

Spranger J, Kroke A, Möhlig M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes. 2003 Mar;52(3):812-817. doi:10.2337/diabetes.52.3.812.

Wannamethee SG, Papacosta O, Lawlor DA, et al. Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women's Heart Health Study. Diabetologia. 2012 Jan;55(1):80-87. doi:10.1007/s00125-011-2284-4.

Jafar N, Edriss H, Nugent K. The Effect of Short-Term Hyperglycemia on the Innate Immune System. Am J Med Sci. 2016 Feb;351(2):201-211. doi:10.1016/j.amjms.2015.11.011.

Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004 Jan;25(1):4-7. doi:10.1016/j.it.2003.10.013.

Banerjee M, Saxena M. Interleukin-1 (IL-1) family of cytokines: role in type 2 diabetes. Clin Chim Acta. 2012 Aug 16;413(15-16):1163-1170. doi:10.1016/j.cca.2012.03.021.

Dror E, Dalmas E, Meier DT, et al. Postprandial macrophage-derived IL-1β stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat Immunol. 2017 Mar;18(3):283-292. doi:10.1038/ni.3659.

Herder C, Brunner EJ, Rathmann W, et al. Elevated levels of the anti-inflammatory interleukin-1 receptor antagonist precede the onset of type 2 diabetes: the Whitehall II study. Diabetes Care. 2009 Mar;32(3):421-423. doi:10.2337/dc08-1161.

Carstensen M, Herder C, Kivimäki M, et al. Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes. 2010 May;59(5):1222-1227. doi:10.2337/db09-1199.

Herder C, Baumert J, Thorand B, et al. Chemokines and incident coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002. Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2147-2152. doi:10.1161/01.ATV.0000235691.84430.86.

Urwyler SA, Schuetz P, Ebrahimi F, Donath MY, Christ-Crain M. Interleukin-1 antagonism decreases cortisol levels in obese individuals. J Clin Endocrinol Metab. 2017 May 1;102(5):1712-1718. doi:10.1210/jc.2016-3931.

Cartier A, Lemieux I, Alméras N, Tremblay A, Bergeron J, Després JP. Visceral obesity and plasma glucose-insulin homeostasis: contributions of interleukin-6 and tumor necrosis factor-alpha in men. J Clin Endocrinol Metab. 2008 May;93(5):1931-1938. doi:10.1210/jc.2007-2191.

Goyal R, Faizy AF, Siddiqui SS, Singhai M. Evaluation of TNF-α and IL-6 Levels in Obese and Non-obese Diabetics: Pre- and Postinsulin Effects. N Am J Med Sci. 2012 Apr;4(4):180-184. doi:10.4103/1947-2714.94944.

Hansen D, Dendale P, Beelen M, et al. Plasma adipokine and inflammatory marker concentrations are altered in obese, as opposed to non-obese, type 2 diabetes patients. Eur J Appl Physiol. 2010 Jun;109(3):397-404. doi:10.1007/s00421-010-1362-5.

Herder C, Zierer A, Koenig W. Elevated serum levels of transforming growth factor-beta1 (TGFbeta-1) precede the development of type 2 diabetes: MONICA/KORA Augsburg case-cohort study, 1984-2002. In: Minutes of the 44th Genral Assembly of the European Association for the Study of Diabetes. Diabetologia. 2009;52(Suppl 1):A837. doi:10.1007/s00125-009-1445-1.

Thorand B, Kolb H, Baumert J, et al. Elevated levels of interleukin-18 predict the development of type 2 diabetes: results from the MONICA/KORA Augsburg Study, 1984-2002. Diabetes. 2005 Oct;54(10):2932-2938. doi:10.2337/diabetes.54.10.2932.

Zak KP, Mankovsky BN, Kondratska IN, et al. Immunity in patients with type 2 diabetes mellitus with concomitant metabolic syndrome/obesity. Communication 1. Composition of blood leukocytes, immunophenotype of lymphocytes, and ultrastructure of neutrophils. Endokrynologia. 2013;18(1):27-36. (in Russian).

Ellingsgaard H, Hauselmann I, Schuler B, et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011 Oct 30;17(11):1481-1489. doi:10.1038/nm.2513.

Wueest S, Laesser CI, Böni-Schnetzler M, et al. IL-6-Type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion. Diabetes. 2018 Jan;67(1):36-45. doi:10.2337/db17-0637.

Orlenko VL, Zak KP. Treatment with glucagon-like peptide-1 analogues - a breakthrough in diabetes mellitus type 2 therapy. Mìžnarodnij endokrinologìčnij žurnal. 2014;(60):112-117. doi:10.22141/2224-0721.4.60.2014.76690. (in Russian).

Wang X, Bao W, Liu J, et al. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2013 Jan;36(1):166-175. doi:10.2337/dc12-0702.

Daniele G, Guardado Mendoza R, et al. The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol. 2014 Feb;51(1):123-131. doi:10.1007/s00592-013-0543-1.

Hang H, Yuan S, Yang Q, Yuan D, Liu Q. Multiplex bead array assay of plasma cytokines in type 2 diabetes mellitus with diabetic retinopathy. Mol Vis. 2014 Aug 4;20:1137-11345.

Kopecky J, Krusinova E, Wohl P. Effect of 24-hour hypertriglyceridaemia on tumor necrosis factor alpha and resistin in type 2 diabetes and healthy subjects. In: Minutes of the 43rd General Assembly of the European Association for the Study of Diabetes. Diabetologia. 2008;51(Suppl 1):322. doi:10.1007/s00125-008-1117-6.

Lindmark S, Burén J, Eriksson JW. Insulin resistance, endocrine function and adipokines in type 2 diabetes patients at different glycaemic levels: potential impact for glucotoxicity in vivo. Clin Endocrinol (Oxf). 2006 Sep;65(3):301-309. doi:10.1111/j.1365-2265.2006.02593.x.

Mishima Y, Kuyama A, Tada A, Takahashi K, Ishioka T, Kibata M. Relationship between serum tumor necrosis factor-alpha and insulin resistance in obese men with Type 2 diabetes mellitus. Diabetes Res Clin Pract. 2001 May;52(2):119-123. doi:10.1016/s0168-8227(00)00247-3.

Su SC, Pei D, Hsieh CH, Hsiao FC, Wu CZ, Hung YJ. Circulating pro-inflammatory cytokines and adiponectin in young men with type 2 diabetes. Acta Diabetol. 2011 Jun;48(2):113-119. doi:10.1007/s00592-009-0171-y.

Zak KP, Mankovsky BN, Melnichenko SV, et al. Immunity in patients with type 2 diabetes mellitus in complex with concomitant metabolic syndrome/obesity. Communication 2. Role of adipocytokines (interleukin-6, tumor necrosis factor alpha, leptin and adiponectin). Endokrynologia. 2013;18(2):26-32. (in Russian).

Zak KP, Furmanova OV. Immune and anti-inflammatory factors in the mechanism of therapeutic effect of metformin in type 2 diabetes mellitus (analytical review including the results of own researches). Mìžnarodnij endokrinologìčnij žurnal. 2018;14(2):173-181. doi:10.22141/2224-0721.14.2.2018.130564. (in Russian).

Zhao Z, Tang X, Song K, Li X, Zhang Y. Association of -308G/A and -238G/A polymorphisms of TNF-α and osteosarcoma risk. Int J Clin Exp Pathol. 2015 Apr 1;8(4):4177-4181.

Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005 Nov;6(11):1123-1132. doi:10.1038/ni1254.

Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005 Nov;6(11):1133-1141. doi:10.1038/ni1261.

Zak KP, Popova VV. The role of IL-17 in the pathogenesis of type 1 and type 2 diabetes mellitus in humans. Mìžnarodnij endokrinologìčnij žurnal. 2018;14(5):514-521. doi:10.22141/2224-0721.14.5.2018.142690. (in Russian).

Fatima N, Faisal SM, Zubair S, Siddiqui SS, Moin S, Owais M. Emerging role of Interleukins IL-23/IL-17 axis and biochemical markers in the pathogenesis of Type 2 Diabetes: Association with age and gender in human subjects. Int J Biol Macromol. 2017 Dec;105(Pt 1):1279-1288. doi:10.1016/j.ijbiomac.2017.07.155.

Fores JP, Crisostomo LG, Orii NM, et al. Th17 pathway in recent-onset autoimmune diabetes. Cell Immunol. 2018 Feb;324:8-13. doi:10.1016/j.cellimm.2017.11.005.

Zhang C, Xiao C, Wang P, et al. The alteration of Th1/Th2/Th17/Treg paradigm in patients with type 2 diabetes mellitus: Relationship with diabetic nephropathy. Hum Immunol. 2014 Apr;75(4):289-296. doi:10.1016/j.humimm.2014.02.007.

Chen C, Shao Y, Wu X, Huang C, Lu W. Elevated interleukin-17 levels in patients with newly diagnosed type 2 diabetes mellitus. Biochem Physiol. 2016;5(206):2-10.  doi:10.4172/2168-9652.1000206.

Fabbrini E, Cella M, McCartney SA, et al. Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology. 2013 Aug;145(2):366-74.e1-3. doi:10.1053/j.gastro.2013.04.010.

Ohashi K, Ouchi N, Matsuzawa Y. Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie. 2012 Oct;94(10):2137-2142. doi:10.1016/j.biochi.2012.06.008.

Roohi A, Tabrizi M, Abbasi F, et al. Serum IL-17, IL-23, and TGF-β levels in type 1 and type 2 diabetic patients and age-matched healthy controls. Biomed Res Int. 2014;2014:718946. doi:10.1155/2014/718946.

Zak KP, Furmanova OV, Popova VV, Sayenko YaA. The content of pro-inflammatory cytokines IL-1β, IL-6, IL-17A and TNFα in the blood of patients with type 2 diabetes after therapy with metformin. Ukr Biochem J. 2020;92(6):105-112. doi:10.15407/ubj92.06.105.

Abdel-Moneim A, Bakery HH, Allam G. The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus. Biomed Pharmacother. 2018 May;101:287-92. doi:10.1016/j.biopha.2018.02.103.

Ho KT, Shiau MY, Chang YH, Chen CM, Yang SC, Huang CN. Association of interleukin-4 promoter polymorphisms in Taiwanese patients with type 2 diabetes mellitus. Metabolism. 2010 Dec;59(12):1717-1722. doi:10.1016/j.metabol.2010.04.010.

Silva-Filho JL, Caruso-Neves C, Pinheiro AAS. IL-4: an important cytokine in determining the fate of T cells. Biophys Rev. 2014 Mar;6(1):111-118. doi:10.1007/s12551-013-0133-z.

Sartangello C, Marchetti P, Marselli L. Suppressors of cytokine signaling (SOCS) in cytokine-induced human islet cell damage. In: Abstracts of the 37th Annual Meeting of the EASD. 2001, September 9-13; Glasgow, United Kingdom. Diabetologia. 2001;44(Suppl 1):A41. doi:10.1007/BF03180172.

Te Velde AA, Huijbens RJ, Heije K, de Vries JE, Figdor CG. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood. 1990 Oct 1;76(7):1392-1397.

Cheung DL, Hart PH, Vitti GF, Whitty GA, Hamilton JA. Contrasting effects of interferon-gamma and interleukin-4 on the interleukin-6 activity of stimulated human monocytes. Immunology. 1990 Sep;71(1):70-75.

Binisor ID, Moldovan R, Moldovan I, Andrei AM, Banita MI. Abdominal Obesity and Type 2 Diabetes Mellitus are Associated With Higher Seric Levels of IL 4 in Adults. Curr Health Sci J. 2016 Jul-Sep;42(3):231-237. doi:10.12865/CHSJ.42.03.03.

Shiau MY, Chuang PH, Yang CP, et al. Mechanism of Interleukin-4 Reducing Lipid Deposit by Regulating Hormone-Sensitive Lipase. Sci Rep. 2019 Aug 19;9(1):11974. doi:10.1038/s41598-019-47908-9.

Alsaid A, El-Missiry M, Hatata el-S, Tarabay M, Settin A. Association of IL-4-590 C>T and IL-13-1112 C>T gene polymorphisms with the susceptibility to type 2 diabetes mellitus. Dis Markers. 2013;35(4):243-247. doi:10.1155/2013/107470.

Blüher M, Fasshauer M, Tönjes A, Kratzsch J, Schön MR, Paschke R. Association of interleukin-6, C-reactive protein, interleukin-10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism. Exp Clin Endocrinol Diabetes. 2005 Oct;113(9):534-537. doi:10.1055/s-2005-872851.

Esposito K, Pontillo A, Giugliano F, et al. Association of low interleukin-10 levels with the metabolic syndrome in obese women. J Clin Endocrinol Metab. 2003 Mar;88(3):1055-1058. doi:10.1210/jc.2002-021437.

Van Exel E, Gussekloo J, de Craen AJ, et al. Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: the Leiden 85-Plus Study. Diabetes. 2002 Apr;51(4):1088-1092. doi:10.2337/diabetes.51.4.1088.

Straczkowski M, Kowalska I, Nikolajuk A, Krukowska A, Gorska M. Plasma interleukin-10 concentration is positively related to insulin sensitivity in young healthy individuals. Diabetes Care. 2005 Aug;28(8):2036-2037. doi:10.2337/diacare.28.8.2036.

Kim YH, Pyo S. Interleukin-10 suppresses adipogenesis via Wnt5a signaling pathway in 3T3-L1 preadipocytes. Biochem Biophys Res Commun. 2019 Feb 19;509(4):877-885. doi:10.1016/j.bbrc.2019.01.033.

Canecki-Varžić S, Prpić-Križevac I, Mihaljević S, et al. Association Between Interleukin-10 Gene (-1082g/A) Polymorphism and Type 2 Diabetes, Diabetes-Related Traits, and Microvascular Complications in the Croatian Population. Acta Clin Croat. 2018 Mar;57(1):71-81. doi:10.20471/acc.2018.57.01.08.

Zhang Z, Yuan W, Sun L, et al. 1,25-Dihydroxyvitamin D3 targeting of NF-kappaB suppresses high glucose-induced MCP-1 expression in mesangial cells. Kidney Int. 2007 Jul;72(2):193-201. doi:10.1038/sj.ki.5002296.

Coll B, Alonso-Villaverde C, Joven J. Monocyte chemoattractant protein-1 and atherosclerosis: is there room for an additional biomarker? Clin Chim Acta. 2007 Aug;383(1-2):21-29. doi:10.1016/j.cca.2007.04.019.

Chow FY, Nikolic-Paterson DJ, Ozols E, Atkins RC, Rollin BJ, Tesch GH. Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice. Kidney Int. 2006 Jan;69(1):73-80. doi:10.1038/sj.ki.5000014.

Zorena K, Mysliwska J, Lipowski P. Chemokines in aqueous humor and serum in patients with cataract and proliferative diabetic retinopathy: a preliminary study. In: Abstracts of the 3rd International Congress on Prediabetes and the Metabolic Syndrome. 2009; April 1-4; Nice, France. J Diabetes. 2009;1(Suppl 1):A165. doi:10.1111/j.1753-0407.2009.00020.x.

Müller S, Martin S, Koenig W, et al. Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors. Diabetologia. 2002 Jun;45(6):805-812. doi:10.1007/s00125-002-0829-2.

Zozuliñska D, Majchrzak A, Sobieska M, Wiktorowicz K, Wierusz-Wysocka B. Serum interleukin-8 level is increased in diabetic patients. Diabetologia. 1999 Jan;42(1):117-118. doi:10.1007/s001250051124.

Aukrust P, Halvorsen B, Yndestad A, et al. Chemokines and cardiovascular risk. Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1909-1919. doi:10.1161/ATVBAHA.107.161240.

Hernández C, Segura RM, Fonollosa A, Carrasco E, Francisco G, Simó R. Interleukin-8, monocyte chemoattractant protein-1 and IL-10 in the vitreous fluid of patients with proliferative diabetic retinopathy. Diabet Med. 2005 Jun;22(6):719-722. doi:10.1111/j.1464-5491.2005.01538.x.

Maedler K, Santer NS, Schulthess FT. The chemokine IP-10 induces beta cell death through TLR-4 signaling. In: 40th EASD Annual Meeting of the European Association for the Study of Diabetes. 2004, September 5-9; Munich, Germany. Diabetologia. 2004;47(Suppl 1):A158. doi:10.1007/BF03375463.

Shah R, Hinkle CC, Ferguson JF, et al. Fractalkine is a novel human adipochemokine associated with type 2 diabetes. Diabetes. 2011 May;60(5):1512-1518. doi:10.2337/db10-0956.

Zak KP, Kondratskaia IN, Mel'nichenko SV, Popova VV. Circulating interleukin-16 in blood of patients with metabolic syndrome and type 2 diabetes mellitus. Lik Sprava. 2007 Jul-Sep;(5-6):46-49. (in Russian).

Scherer PE. The Multifaceted Roles of Adipose Tissue-Therapeutic Targets for Diabetes and Beyond: the 2015 Banting Lecture. Diabetes. 2016 Jun;65(6):1452-1461. doi:10.2337/db16-0339.

Zhao S, Kusminski CM, Elmquist JK, Scherer PE. Leptin: Less Is More. Diabetes. 2020 May;69(5):823-829. doi:10.2337/dbi19-0018.

Schmidt MI, Duncan BB, Vigo A, et al. Leptin and incident type 2 diabetes: risk or protection? Diabetologia. 2006 Sep;49(9):2086-2096. doi:10.1007/s00125-006-0351-z.

Snijder MB, Heine RJ, Seidell JC, et al. Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women: the hoorn study. Diabetes Care. 2006 Nov;29(11):2498-2503. doi:10.2337/dc06-0952.

Li VL, Kim JT, Long JZ. Adipose tissue lipokines: recent progress and future directions. Diabetes. 2020 Dec;69(12):2541-2548. doi:10.2337/dbi20-0012.

Kondratska I, Zak K, Mankovsky B. Plasma levels of leptin and adiponectin in patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MS). In: Abstracts of the 3rd International Congress on Prediabetes and the Metabolic Syndrome. 2009; April 1-4; Nice, France. J Diabetes. 2009;1(Suppl 1):A172. doi:10.1111/j.1753-0407.2009.00020.x.

German JP, Wisse BE, Thaler JP, et al. Leptin deficiency causes insulin resistance induced by uncontrolled diabetes. Diabetes. 2010 Jul;59(7):1626-1634. doi:10.2337/db09-1918.

Hanley AJ, Wagenknecht LE, Norris JM, et al. Adiponectin and the incidence of type 2 diabetes in Hispanics and African Americans: the IRAS Family Study. Diabetes Care. 2011 Oct;34(10):2231-2236. doi:10.2337/dc11-0531.

Rasmusen MS, Lihn AS, Bruun JM. Regulation of adiponectin receptor 1 and 2 in human adipose tissue. In: 40th EASD Annual Meeting of the European Association for the Study of Diabetes. 2004, September 5-9; Munich, Germany. Diabetologia. 2004;47(Suppl 1):A76. doi:10.1007/BF03375463.

Rewers M, Maahs D, Wadwa P. Adiponectin and soluble IL-2 receptor levels predict progression of coronary artery calcification in type 1 diabetes. In: 40th EASD Annual Meeting of the European Association for the Study of Diabetes. 2004, September 5-9; Munich, Germany. Diabetologia. 2004;47(Suppl 1):A47. doi:10.1007/BF03375463.

Rubin D, Helwig U, Lemke N. Postprandial adiponectin levels after an oral lipid tolerance test versus oral glucose tolerance test and association with parameters of the metabolic syndrome. In: 40th EASD Annual Meeting of the European Association for the Study of Diabetes. 2004, September 5-9; Munich, Germany. Diabetologia. 2004;47(Suppl 1):A227. doi:10.1007/BF03375463.

Sattar N, McConnachie A, Shaper AG, et al. Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies. Lancet. 2008 Jun 7;371(9628):1927-1935. doi:10.1016/S0140-6736(08)60602-9.

Stefan N, Machicao F, Staiger H, et al. Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat. Diabetologia. 2005 Nov;48(11):2282-2291. doi:10.1007/s00125-005-1948-3.

Wannamethee SG, Lowe GD, Rumley A, Cherry L, Whincup PH, Sattar N. Adipokines and risk of type 2 diabetes in older men. Diabetes Care. 2007 May;30(5):1200-1205. doi:10.2337/dc06-2416.

Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2009 Jul 8;302(2):179-188. doi:10.1001/jama.2009.976.

Turer AT, Scherer PE. Adiponectin: mechanistic insights and clinical implications. Diabetologia. 2012 Sep;55(9):2319-2326. doi:10.1007/s00125-012-2598-x.

Tate J, Knuiman M, Davis WA, Davis TME, Bruce DG. A comparison of obesity indices in relation to mortality in type 2 diabetes: the Fremantle Diabetes Study. Diabetologia. 2020 Mar;63(3):528-536. doi:10.1007/s00125-019-05057-8.

Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979 May 11;241(19):2035-2038. doi:10.1001/jama.241.19.2035.

Bottle A, Millett C, Khunti K, Majeed A. Trends in cardiovascular admissions and procedures for people with and without diabetes in England, 1996-2005. Diabetologia. 2009 Jan;52(1):74-80. doi:10.1007/s00125-008-1170-1.

Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care. 2014 Oct;37(10):2864-2883. doi:10.2337/dc14-1296.

Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010 Jul 10;376(9735):124-136. doi:10.1016/S0140-6736(09)62124-3.

Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med. 2012 Mar 29;366(13):1227-1239. doi:10.1056/NEJMra1005073.

Kumar S, Wilson B, Watson L, Alsop J. Obesity is associated with poorer clinical outcomes following insulin initiation for patients with type 2 diabetes. In: Abstracts of the 45th General Assembly of the European Association for the Study of Diabetes. 2009, September 30 - October 2; Vienna, Austria. Diabetologia. 2009;52(Suppl 1):1-550. doi:10.1007/s00125-009-1445-1.

Lichiardopol R, Popescu LD, Ionescu I, Dovan D, Pencea C. Abdominal obesity in type 1 and type 2 diabetes patients. In: Abstracts of the 44th Annual Meeting of the European Association for the Study of Diabetes. 2008; September 8-11; Rome, Italy. Diabetologia. 2008;51(Suppl 1):S335. doi:10.1007/s00125-008-1117-6.

Scheja L, Heeren J. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat Rev Endocrinol. 2019 Sep;15(9):507-524. doi:10.1038/s41574-019-0230-6.

Cox AR, Chernis N, Bader DA, et al. STAT1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity in Obesity. Diabetes. 2020 Dec;69(12):2630-2641. doi:10.2337/db20-0384.

Donath MY, Dalmas É, Sauter NS, Böni-Schnetzler M. Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity. Cell Metab. 2013 Jun 4;17(6):860-872. doi:10.1016/j.cmet.2013.05.001.

Kim JY, Bacha F, Tfayli H, Michaliszyn SF, Yousuf S, Arslanian S. Adipose Tissue Insulin Resistance in Youth on the Spectrum From Normal Weight to Obese and From Normal Glucose Tolerance to Impaired Glucose Tolerance to Type 2 Diabetes. Diabetes Care. 2019 Feb;42(2):265-272. doi:10.2337/dc18-1178.

Kopelman PG. Obesity as a medical problem. Nature. 2000 Apr 6;404(6778):635-643. doi:10.1038/35007508.

Harwood HJ Jr. The adipocyte as an endocrine organ in the regulation of metabolic homeostasis. Neuropharmacology. 2012 Jul;63(1):57-75. doi:10.1016/j.neuropharm.2011.12.010.

Almuraikhy S, Kafienah W, Bashah M, et al. Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance. Diabetologia. 2016 Nov;59(11):2406-2416. doi:10.1007/s00125-016-4031-3.

Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004 Jun;89(6):2548-2556. doi:10.1210/jc.2004-0395.

Trayhurn P, Bing C. Appetite and energy balance signals from adipocytes. Philos Trans R Soc Lond B Biol Sci. 2006 Jul 29;361(1471):1237-1249. doi:10.1098/rstb.2006.1859.

Nolan JJ, Færch K. Estimating insulin sensitivity and beta cell function: perspectives from the modern pandemics of obesity and type 2 diabetes. Diabetologia. 2012 Nov;55(11):2863-2867. doi:10.1007/s00125-012-2684-0.

Tron'ko ND, Zak KP. Obesity and diabetes mellitus. Lik Sprava. 2013 Dec;(8):3-21. (in Russian).

Di Angelantonio E, Bhupathiraju ShN, Wormser D, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016 Aug 20;388(10046):776-786. doi:10.1016/S0140-6736(16)30175-1.

Boutens L, Stienstra R. Adipose tissue macrophages: going off track during obesity. Diabetologia. 2016 May;59(5):879-894. doi:10.1007/s00125-016-3904-9.

McLaughlin T, Abbasi F, Lamendola C, et al. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation. 2002 Dec 3;106(23):2908-2912. doi:10.1161/01.cir.0000041046.32962.86.

Guarino D, Antonioli L, Fornai M, et al. Diabetes, obesity and inflammation: Persistence of elevated IL-1b after bariatric surgery. In: 53rd EASD Annual Meeting of the European Association for the Study of Diabetes. 2017, September 11-15; Lisbon, Portugal. Diabetologia. 2017;60(Suppl 1):1-97. doi:10.1007/s00125-017-4350-z.

Somm E, Cettour-Rose P, Asensio C, еt al. Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents. Diabetologia. 2006 Feb;49(2):387-393. doi:10.1007/s00125-005-0046-x.

Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001 May;280(5):E745-751. doi:10.1152/ajpendo.2001.280.5.E745.

De Carvalho MH, Colaço AL, Fortes ZB. Cytokines, endothelial dysfunction, and insulin resistance. Arq Bras Endocrinol Metabol. 2006 Apr;50(2):304-312. doi:10.1590/s0004-27302006000200016. (in Portuguese).

Ryu O, Kim H, Shin D. Effects of exercise on inflammatory markers, insulin resistance, and arterial stiffness. In: 42nd EASD Annual Meeting of the European Association for the Study of Diabetes. 2006, September 14-17; Copenhagen, Denmark. Diabetologia. 2006;49(Suppl 1):470. doi:10.1007/s00125-006-0358-5.

Sumarac-Dumanovic M, Stevanovic D, Ljubic A, et al. Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. Int J Obes (Lond). 2009 Jan;33(1):151-156. doi:10.1038/ijo.2008.216.

Laouali N, Mancini FR, Hajji-Louati M, et al. Dietary inflammatory index and type 2 diabetes risk in a prospective cohort of 70991 women followed for 20 years: the mediating role of BMI. Diabetologia. 2019 Dec;62(12):2222-2232. doi:10.1007/s00125-019-04972-0.

Formoso G, Baldassarre MPA, Taraborrelli M, et al. Visceral fat reduction is associated with increased IL 10 levels in obese subjects that underwent caloric restriction. In: Abstracts of the 46th General Assembly of the European Association for the Study of Diabetes (EASD). 2010, September 20-24; Stockholm, Sweden. Diabetologia. 2010 Sep;53(Suppl 1):A783. doi:10.1007/s00125-010-1872-z.

Campbell JJ, Hedrick J, Zlotnik A, Siani MA, Thompson DA, Butcher EC. Chemokines and the arrest of lymphocytes rolling under flow conditions. Science. 1998 Jan 16;279(5349):381-384. doi:10.1126/science.279.5349.381.

Fernández-Real JM, Pickup JC. Innate immunity, insulin resistance and type 2 diabetes. Diabetologia. 2012 Feb;55(2):273-278. doi:10.1007/s00125-011-2387-y.

Mazurek T. Local epicardial adipose tissue inflammation is associated with serum insulin and insulin resistance in patients with advanced coronary artery disease. In: 40th EASD Annual Meeting of the European Association for the Study of Diabetes. 2004, September 5-9; Munich, Germany. Diabetologia. 2004;47(Suppl 1):A31. doi:10.1007/BF03375463.

Murdolo G, Hammarstedt A, Sandqvist M, et al. Monocyte chemoattractant protein-1 in subcutaneous abdominal adipose tissue: characterization of interstitial concentration and regulation of gene expression by insulin. J Clin Endocrinol Metab. 2007 Jul;92(7):2688-2695. doi:10.1210/jc.2006-2814.

Ouwens DM, Bekaeri M, Lapauw B, Lehr S, Hartwig S, Herzfeld de Wiza D. Sex steroid-induced changes in circulating monocyte  chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men. In: Abstracts of the 48th EASD Annual Meeting. 2012; October 1-5; Berlin, Germany. Diabetologia. 2012;55(Suppl 1):A654. doi:10.1007/s00125-012-2688-9.

Fukami A, Adachi H, Yamagishi S-I, et al. A strong association betweem serum level of monocyte chemoattractant protein 1 (MCP-1) and insulin resistant syndrome. In: Minutes of the 42nd General Assembly of the European Association for the Study of Diabetes Annual Meeting. 2006, September 16; Copenhagen, Denmark. Diabetologia. 2007 Sep;50(Suppl 1):S166. doi:10.1007/s00125-007-0809-7.

Nio Y, Yamauchi T, Iwabu M, et al. Monocyte chemoattractant protein-1 (MCP-1) deficiency enhances alternatively activated M2 macrophages and ameliorates insulin resistance and fatty liver in lipoatrophic diabetic A-ZIP transgenic mice. Diabetologia. 2012 Dec;55(12):3350-3358. doi:10.1007/s00125-012-2710-2.

Farooqi IS, O'Rahilly S. Leptin: a pivotal regulator of human energy homeostasis. Am J Clin Nutr. 2009 Mar;89(3):980S-984S. doi:10.3945/ajcn.2008.26788C.

Scott EM, Grant PJ. Neel revisited: the adipocyte, seasonality and type 2 diabetes. Diabetologia. 2006 Jul;49(7):1462-1466. doi:10.1007/s00125-006-0280-x.

Lönnqvist F, Nordfors L, Schalling M. Leptin and its potential role in human obesity. J Intern Med. 1999 Jun;245(6):643-652. doi:10.1046/j.1365-2796.1999.00493.x.

Winkler G, Baranyi E, Melczer Z. Role of TNF-α system and leptin in insulin resistance in patients with gestational diabetes. In: 36th EASD Annual Meeting of the European Association for the Study of Diabetes. 2000, Septemeber 17-21; Jerusalem, Israel. Diabetologia. 2000;43(Suppl 1):A172. doi:10.1007/BF03375455.

Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006 Dec 14;444(7121):860-867. doi:10.1038/nature05485.

Dalmas E, Venteclef N, Caer C, et al. T cell-derived IL-22 amplifies IL-1β-driven inflammation in human adipose tissue: relevance to obesity and type 2 diabetes. Diabetes. 2014 Jun;63(6):1966-1977. doi:10.2337/db13-1511.

Hoffstedt J, Andersson DP, Eriksson Hogling D, et al. Long-term protective changes in adipose tissue after gastric bypass. Diabetes Care. 2017 Jan;40(1):77-84. doi:10.2337/dc16-1072.

Top C, Uslu SA, Onde ME. The relationship between body surface area and insulin resistance, serum IL-6 levels in patients with type 2 diabetes. In: Abstracts of the 3rd International Congress on Prediabetes and the Metabolic Syndrome. 2009; April 1-4; Nice, France. J Diabetes. 2009;1(Suppl 1):A167-168. doi:10.1111/j.1753-0407.2009.00020.x.

Seyhan A, Nunez-Lopez Yu, Garufi G. Differences in serum cytokine concentrations in lean and obese individuals with prediabetes and type 2 diabetes. In: 75th American Diabetes Association (ADA) Scientific Sessions. 2015, June 05-09; Boston, Massachusetts. Diabetes. 2015;64(Suppl 1):A472. doi:10.2337/db15-1801-1846.

Ellingsgaard H, Seelig E, Timper K, et al. GLP-1 secretion is regulated by IL-6 signalling: a randomised, placebo-controlled study. Diabetologia. 2020 Feb;63(2):362-373. doi:10.1007/s00125-019-05045-y.

Grosz A, Nagy E, Halmos T. Inflammatory parametwers in type 2 diabetics and in the metabolic syndrome. In: 42nd EASD Annual Meeting of the European Association for the Study of Diabetes. 2006, September 14-17; Copenhagen, Denmark. Diabetologia. 2006;49(Suppl 1):446. doi:10.1007/s00125-006-0358-5.

Monroy A, Kamath S, Chavez AO, et al. Impaired regulation of the TNF-alpha converting enzyme/tissue inhibitor of metalloproteinase 3 proteolytic system in skeletal muscle of obese type 2 diabetic patients: a new mechanism of insulin resistance in humans. Diabetologia. 2009 Oct;52(10):2169-2181. doi:10.1007/s00125-009-1451-3.

Aas A-M, Seljeflot I, Birkeland KI. Effects of lifestyle intervention and insulin treatment on PAI-1, Hs-CRP and TNF-α levels in patients with type 2 diabetes. In: 40th EASD Annual Meeting of the European Association for the Study of Diabetes. 2004, September 5-9; Munich, Germany. Diabetologia. 2004;47(Suppl 1):A295. doi:10.1007/BF03375463.

Zahorska-Markiewicz B, Janowska J, Olszanecka-Glinianowicz M, Zurakowski A. Serum concentrations of TNF-alpha and soluble TNF-alpha receptors in obesity. Int J Obes Relat Metab Disord. 2000 Nov;24(11):1392-1395. doi:10.1038/sj.ijo.0801398.

De Carvalho MH, Colaço AL, Fortes ZB. Cytokines, endothelial dysfunction, and insulin resistance. Arq Bras Endocrinol Metabol. 2006 Apr;50(2):304-312. doi:10.1590/s0004-27302006000200016. (in Portuguese).

Nikolajczyk BS, Zhu M, Blanche IP, et al. An inflammatory T.cell signature predicts obesity-associated type2 diabetes. In: 75th American Diabetes Association (ADA) Scientific Sessions. 2015, June 05-09; Boston, Massachusetts. Diabetes. 2015;64(Suppl 1):A62-234. doi:10.2337/db15-1-385.

Baig S, Rizi EP, Shabeer M, et al. Acute meall challenge and modulation of postprandial immune metabolic response in peripheral blood mononuclear cells, in lean, insulin sensitive and obese, insulin resistant Chinese. In: 75th American Diabetes Association (ADA) Scientific Sessions. 2015, June 05-09; Boston, Massachusetts. Diabetes. 2015;64(Suppl 1):A467. doi:10.2337/db15-1801-1846.

Chang Y, Piao SL, Gao S, Zheng DM. Regulatory effects of micronutrient complex on the expression of Th1 and Th2 cytokines in diabetic C57BL mice. Wei Sheng Yan Jiu. 2005 Jan;34(1):64-66. (in Chinese).

Erdmann J, Lippl F, Wagenpfeil S, Schusdziarra V. Differential association of basal and postprandial plasma ghrelin with leptin, insulin, and type 2 diabetes. Diabetes. 2005 May;54(5):1371-1378. doi:10.2337/diabetes.54.5.1371.

Zimmet PZ, Magliano DJ, De Courten B. Cytokines, advanced glycation end-products, leptin, adiponectin and diabetes: a nested case-control study. In: Minutes of the 43rd General Assembly of the European Association for the Study of Diabetes. Diabetologia. 2008;51(Suppl 1):S86. doi:10.1007/s00125-008-1117-6.

Lilja M, Rolandsson O, Norberg M. Leptin independently predicts diabetes in Swedish men. In: Abstracts of the 46th General Assembly of the European Association for the Study of Diabetes (EASD). 2010, September 20-24; Stockholm, Sweden. Diabetologia. 2010 Sep;53(Suppl 1):A394. doi:10.1007/s00125-010-1872-z.

Kautzky-Willer A, Pacini G, Tura A, et al. Increased plasma leptin in gestational diabetes. Diabetologia. 2001 Feb;44(2):164-172. doi:10.1007/s001250051595.

Kim SG, Ryu OH, Kim HY, et al. Effect of rosiglitazone on plasma adiponectin levels and arterial stiffness in subjects with prediabetes or non-diabetic metabolic syndrome. Eur J Endocrinol. 2006 Mar;154(3):433-440. doi:10.1530/eje.1.02100.

Kim JY, Ahn SV, Yoon JH, et al. Prospective study of serum adiponectin and incident metabolic syndrome: the ARIRANG study. Diabetes Care. 2013 Jun;36(6):1547-1553. doi:10.2337/dc12-0223.

Krusinova E, Wohl P, Fejfarova V. Effect of acute hyperinsulinaemia on plasma concentrations of selected cytokine antagonists in type 1 diabetes mellitus. In: 40th EASD Annual Meeting of the European Association for the Study of Diabetes. 2004, September 5-9; Munich, Germany. Diabetologia. 2004;47(Suppl 1):A-461. doi:10.1007/BF03375463.

Ong KL, Tso AW, Xu A, et al. Evaluation of the combined use of adiponectin and C-reactive protein levels as biomarkers for predicting the deterioration in glycaemia after a median of 5.4 years. Diabetologia. 2011 Oct;54(10):2552-2560. doi:10.1007/s00125-011-2227-0.

Silva-Nunes J, Duarte I, Veiga L. Should hypoadiponectinemia be included as a component of the metabolic syndrome. In: Abstracts of the 3rd International Congress on Prediabetes and the Metabolic Syndrome. 2009; April 1-4; Nice, France. J Diabetes. 2009;1(Suppl 1):A172. doi:10.1111/j.1753-0407.2009.00020.x.

Menzaghi C, Trischitta V. The Adiponectin Paradox for All-Cause and Cardiovascular Mortality. Diabetes. 2018 Jan;67(1):12-22. doi:10.2337/dbi17-0016.

Schrieks IC, Nozza A, Stähli BE, et al. Adiponectin, Free Fatty Acids, and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Acute Coronary Syndrome. Diabetes Care. 2018 Aug;41(8):1792-1800. doi:10.2337/dc18-0158.

McGonagle D, Sharif K, O'Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020 Jun;19(6):102537. doi:10.1016/j.autrev.2020.102537.

Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi:10.1016/S0140-6736(20)30628-0.

Crouse A, Grimes T, Li P, Might M, Ovalle F, Shalev A. Metformin use is associated with reduced mortality in a diverse population with Covid-19 and diabetes. medRxiv. 2020 Jul 31:2020.07.29.20164020. doi:10.1101/2020.07.29.20164020.

Ugwueze CV, Ezeokpo BC, Nnolim BI, Agim EA, Anikpo NC, Onyekachi KE. COVID-19 and diabetes mellitus: The link and clinical implications. Dubai Diabetes Endocrinol J. 2020;26(2):69-77. doi:10.1159/000511354.

Varghese E, Samuel SM, Liskova A, Kubatka P, Büsselberg D. Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing. PLoS Pathog. 2021 Jun 22;17(6):e1009634. doi:10.1371/journal.ppat.1009634.

Published

2022-01-12

How to Cite

Zak, K., Popova, V., Orlenko, V., Furmanova, O., & Tronko, N. (2022). Cytokines in the blood of patients with type 2 diabetes mellitus depending on the level of overweight/obesity (literature review and own data). INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), 17(7), 534–551. https://doi.org/10.22141/2224-0721.17.7.2021.244969

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