Resistin is Associated with Inflammation and Renal Function, but not with Insulin Resistance in Type 2 Diabetes

Abstract

The aim of the study was to investigate the association of adipokines (resistin, leptin and adiponectin) with obesity, insulin resistance (IR) and inflammation in type 2 diabetes mellitus (T2DM). A total of 284 patients with T2DM were included. Concentrations of resistin, leptin, adiponectin, and inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)] were measured and homeostatic model assessment for IR (HOMA-IR) index was calculated. Resistin correlated negatively with estimated glomerular filtration rate (eGFR) and positively with hsCRP, TNF-α, IL-6, and white blood cell count (WBC). Leptin correlated positively with HOMA-IR, whereas adiponectin correlated negatively. Leptin also correlated positively with body mass index (BMI), waist circumference, IL-6, WBC and negatively with eGFR. Adiponectin correlated negatively with waist circumference, WBC, and eGFR. Multivariate logistic regression indicated lower eGFR and higher WBC and IL-6 as independent predictive factors of resistin concentration above the upper quartile (CAQ3), whereas female sex and higher BMI and HOMA-IR of leptin CAQ3, and lower HOMA-IR and older age of adiponectin CAQ3. In conclusion, in contrast to leptin and adiponectin, in T2DM patients, resistin is not associated with BMI and IR, but with inflammation and worse kidney function.

Key words

resistin - adipokines - diabetes mellitus - inflammation - renal function - insulin resistance

Publication History

Received: 01 December 2020

Accepted after revision: 19 April 2021

Article published online:
24 June 2021

• References

• 1 Saeedi P, Petersohn I, Salpea P. et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019; 157: 107843
• 2 [Anonymous] Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43: S14-S31
• 3 Cosentino F, Grant PJ, Aboyans V. et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020; 41: 255-323
• 4 Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89: 2548-2556
• 5 Kocot J, Dziemidok P, Kielczykowska M. et al. Adipokine Profile in Patients with Type 2 Diabetes Depends on Degree of Obesity. Med Sci Monitor 2017; 23: 4995-5004
• 6 Liu W, Zhou X, Li Y. et al. Serum leptin, resistin, and adiponectin levels in obese and non-obese patients with newly diagnosed type 2 diabetes mellitus: A population-based study. Medicine 2020; 99: e19052
• 7 Kontunen P, Vuolteenaho K, Nieminen R. et al. Resistin is linked to inflammation, and leptin to metabolic syndrome, in women with inflammatory arthritis. Scand J Rheumatol 2011; 40: 256-262
• 8 Kaplon-Cieslicka A, Postula M, Rosiak M. et al. Association of adipokines and inflammatory markers with lipid control in type 2 diabetes. Polsk Arch Med Wewnetr 2015; 125: 414-423
• 9 Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011; 29: 415-445
• 10 Moreno LO, Salvemini L, Mendonca C. et al. Serum resistin and glomerular filtration rate in patients with type 2 diabetes. PLoS One 2015; 10: e0119529
• 11 Steppan CM, Bailey ST, Bhat S. et al. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307-312
• 12 Huang X, Yang Z. Resistin’s, obesity and insulin resistance: The continuing disconnect between rodents and humans. J Endocrinol Invest 2016; 39: 607-615
• 13 Cebeci E, Cakan C, Gursu M. et al. The Main determinants of serum resistin level in type 2 diabetic patients are renal function and inflammation not presence of microvascular complication, obesity and insulin resistance. Exp Clin Endocrinol Diabetes 2019; 127: 189-194
• 14 Axelsson J, Bergsten A, Qureshi AR. et al. Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. Kidney Int 2006; 69: 596-604
• 15 Kawamura R, Doi Y, Osawa H. et al. Circulating resistin is increased with decreasing renal function in a general Japanese population: the Hisayama Study. Nephrol Dialysis Transplant 2010; 25: 3236-3240
• 16 German JP, Wisse BE, Thaler JP. et al. Leptin deficiency causes insulin resistance induced by uncontrolled diabetes. Diabetes 2010; 59: 1626-1634
• 17 Moon HU, Ha KH, Han SJ. et al. The Association of adiponectin and visceral fat with insulin resistance and beta-cell dysfunction. J Kor. Med Sci 2019; 34: e7
• 18 Uslu S, Kebapci N, Kara M. et al. Relationship between adipocytokines and cardiovascular risk factors in patients with type 2 diabetes mellitus. Exp Therap Med 2012; 4: 113-120
• 19 Postula M, Kaplon-Cieslicka A, Rosiak M. et al. Genetic determinants of platelet reactivity during acetylsalicylic acid therapy in diabetic patients: Evaluation of 27 polymorphisms within candidate genes. J Thromb Haemost 2011; 9: 2291-2301
• 20 Rosiak M, Postula M, Kaplon-Cieslicka A. et al. The effect of doubling the dose of acetylsalicylic acid (ASA) on platelet function parameters in patients with type 2 diabetes and platelet hyperreactivity during treatment with 75 mg of ASA: A subanalysis of the AVOCADO study. Kardiol Pol 2013; 71: 552-557
• 21 Kaplon-Cieslicka A, Rosiak M, Postula M. et al. Predictors of high platelet reactivity during aspirin treatment in patients with type 2 diabetes. Kardiol Pol 2013; 71: 893-902
• 22 Kaplon-Cieslicka A, Postula M, Rosiak M. et al. Younger age, higher body mass index and lower adiponectin concentration predict higher serum thromboxane B2 level in aspirin-treated patients with type 2 diabetes: an observational study. Cardiovasc Diabetol 2014; 13: 112
• 23 Kaplon-Cieslicka A, Tyminska A, Rosiak M. et al. Resistin is a prognostic factor for death in type 2 diabetes. Diabetes/Metab Res Rev 2019; 35: e3098
• 24 Postula M, Janicki PK, Rosiak M. et al. New single nucleotide polymorphisms associated with differences in platelets reactivity in patients with type 2 diabetes treated with acetylsalicylic acid: Genome-wide association approach and pooled DNA strategy. J Thromb Thrombol 2013; 36: 65-73
• 25 Eyileten C, Zaremba M, Janicki PK. et al. Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity but not to Genetic Polymorphisms within BDNF Encoding Gene in Patients with Type 2 Diabetes. Med Sci Monitor 2016; 22: 69-76
• 26 Milanowski L, Pordzik J, Janicki PK. et al. New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid: an observational study. Acta Diabetol 2017; 54: 343-351
• 27 Eyileten C, Mirowska-Guzel D, Milanowski L. et al. Serum brain-derived neurotrophic factor is related to platelet reactivity and metformin treatment in adult patients with type 2 diabetes mellitus. Canad J Diabetes 2019; 43: 19-26
• 28 Park HK, Kwak MK, Kim HJ. et al. Linking resistin, inflammation, and cardiometabolic diseases. Kor J Intern Med 2017; 32: 239-247
• 29 Patel L, Buckels AC, Kinghorn IJ. et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 2003; 300: 472-476
• 30 Engin A. The Pathogenesis of Obesity-Associated Adipose Tissue Inflammation. Adv Exp Med Biol 2017; 960: 221-245
• 31 Park H, Hasegawa G, Obayashi H. et al. Relationship between insulin resistance and inflammatory markers and anti-inflammatory effect of losartan in patients with type 2 diabetes and hypertension. Clin Chim Acta 2006; 374: 129-134
• 32 Chen BH, Song Y, Ding EL. et al. Circulating levels of resistin and risk of type 2 diabetes in men and women: results from two prospective cohorts. Diabetes Care 2009; 32: 329-334
• 33 Su KZ, Li YR, Zhang D. et al. Relation of circulating resistin to insulin resistance in type 2 diabetes and obesity: A systematic review and meta-analysis. Front Physiol 2019; 10: 1399
• 34 Bellia C, Cosma C, Lo Sasso B. et al. Glycated albumin as a glycaemic marker in patients with advanced chronic kidney disease and anaemia: a preliminary report. Scand J Clin Lab Invest 2019; 79: 293-297
• 35 Filkova M, Haluzik M, Gay S. et al. The role of resistin as a regulator of inflammation: Implications for various human pathologies. Clin Immunol (Orlando, Fla) 2009; 133: 157-170
• 36 Mostafazadeh M, Haiaty S, Rastqar A. et al. Correlation Between Resistin Level and Metabolic Syndrome Component: A Review. Horm Metab Res 2018; 50: 521-536
• 37 Acquarone E, Monacelli F, Borghi R. et al. Resistin: A reappraisal. Mech Ageing Develop 2019; 178: 46-63
• 38 Pine GM, Batugedara HM, Nair MG. Here, there and everywhere: Resistin-like molecules in infection, inflammation, and metabolic disorders. Cytokine 2018; 110: 442-451
• 39 Li B, Fang J, Zuo Z. et al. Activation of the porcine alveolar macrophages via toll-like receptor 4/NF-kappaB mediated pathway provides a mechanism of resistin leading to inflammation. Cytokine 2018; 110: 357-366
• 40 Zuniga MC, Raghuraman G, Hitchner E. et al. PKC-epsilon and TLR4 synergistically regulate resistin-mediated inflammation in human macrophages. Atherosclerosis 2017; 259: 51-59
• 41 Thomas MC, Cooper ME, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol 2016; 12: 73-81
• 42 Landray MJ, Wheeler DC, Lip GY. et al. Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study. Am J Kidney Dis 2004; 43: 244-253
• 43 Kielstein JT, Becker B, Graf S. et al. Increased resistin blood levels are not associated with insulin resistance in patients with renal disease. Am J Kidney Dis 2003; 42: 62-66
• 44 Frankel DS, Vasan RS, D'Agostino RB. et al. Resistin, adiponectin, and risk of heart failure the Framingham offspring study. J Am College Cardiol 2009; 53: 754-762
• 45 Ramirez JL, Khetani SA, Zahner GJ. et al. Serum resistin is associated with impaired endothelial function and a higher rate of adverse cardiac events in patients with peripheral artery disease. J Vasc Surg 2019; 69: 497-506
• 46 Abdella NA, Mojiminiyi OA, Moussa MA. et al. Plasma leptin concentration in patients with Type 2 diabetes: relationship to cardiovascular disease risk factors and insulin resistance. Diab Med 2005; 22: 278-285
• 47 Horakova D, Stepanek L, Nagelova R. et al. Total and high-molecular-weight adiponectin levels and prediction of insulin resistance. Endokrynol Pol 2018; 69: 375-380
• 48 Lee JM, Kim SR, Yoo SJ. et al. The relationship between adipokines, metabolic parameters and insulin resistance in patients with metabolic syndrome and type 2 diabetes. J Int Med Res 2009; 37: 1803-1812
• 49 Kaleta D, Makowiec-Dabrowska T, Dziankowska-Zaborszczyk E. et al. Prevalence and socio-demographic correlates of daily cigarette smoking in Poland: results from the Global Adult Tobacco Survey (2009-2010). Int J Occup Med Environ Health 2012; 25: 126-136
• 50 Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004; 27: 1487-1495
• 51 Sarafidis PA, Lasaridis AN, Nilsson PM. et al. Validity and reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and McAuley's indices in patients with hypertension and type II diabetes. J Hum Hypertens 2007; 21: 709-716