Abstract
Background: In rheumatoid arthritis (RA), insulin resistance (IR) is related to inflammatory markers, disease activity, and progression of atherosclerotic changes. Triglyceride-glucose (TyG) index is a relatively new indicator of IR.
Aims: The present study aimed to investigate the relationship between TyG index, disease activity and subclinical atherosclerosis (SCA) in RA patients.
Methods: The present case-control study included 100 RA patients and 50 age- and sex-matched healthy controls. All participants were subjected to careful history taking through clinical examination and standard laboratory assessment. The TyG index was calculated as TyG index = ln (Fasting triglyceride (mg/dL) × fasting glucose (mg/dL))/2. Carotid intima-media thickness (CIMT) measurement was done using B-mode ultrasound.
Results: Patients had significantly higher TyG index as compared to controls. Patients with high disease activity had significantly higher frequency of extraarticular manifestations (39.6% versus 51.6%, p = 0.028), higher Larsen score (3.8 ± 1.3 versus 2.8 ± 1.2, p < 0.001), higher anti-cyclic citrullinated peptide (anti-CCP) levels (median (IQR): 243.1 (205.0-408.0) U/ml versus 99.0 (78.0-332.5), p < 0.001), higher TyG index (4.8 ± 0.22 versus 4.67 ± 0.24, p = 0.006), and higher CIMT (0.87 ± 0.22 versus 0.77 ± 0.17 mm, p = 0.018). Patients with SCA had higher BMI (34.6 ± 6.2 versus 30.5 ± 5.3 Kg/m2, p < 0.001), higher Larsen score (3.7 ± 1.4 versus 3.1 ± 1.3, p = 0.028) and higher TyG index (4.89 ± 0.23 versus 4.64 ± 0.19, p < 0.001). Binary logistic regression analysis identified patients’ age (OR (95% CI): 0.94 (0.89-0.99), p = 0.018), Larsen score (OR (95% CI): 1.93 (1.32-2.82), p = <0.001), anti-CCP (OR (95%): 1.04 (1.02-1.07), p = 0.032), and TyG index (OR (95% CI): 22.67 (2.14-240.4), p = 0.01) as significant predictors of high disease activity in multivariate analysis.
Conclusion: IR estimated by the TyG index is related to disease activity and SCA in RA patients.
Keywords: Rheumatoid arthritis, triglyceride-glucose index, subclinical atherosclerosis, autoimmune disease, insulin resistance (IR), disease.
Graphical Abstract
[1]
Finckh A, Gilbert B, Hodkinson B, et al. Global epidemiology of rheumatoid arthritis. Nat Rev Rheumatol 2022; 18(10): 591-602.
[PMID: 36068354]
[PMID: 36068354]
[2]
Sharma A, Goel A. Pathogenesis of rheumatoid arthritis and its treatment with anti-inflammatory natural products. Mol Biol Rep 2023; 50(5): 4687-706.
[http://dx.doi.org/10.1007/s11033-023-08406-4] [PMID: 37022525]
[http://dx.doi.org/10.1007/s11033-023-08406-4] [PMID: 37022525]
[3]
Khanna N, Kumar A, Pawar SV. A review on rheumatoid arthritis interventions and current developments. Curr Drug Targets 2021; 22(4): 463-83.
[http://dx.doi.org/10.2174/1389450121999201125200558] [PMID: 33243118]
[http://dx.doi.org/10.2174/1389450121999201125200558] [PMID: 33243118]
[4]
Alivernini S, Firestein GS, McInnes IB. The pathogenesis of rheumatoid arthritis. Immunity 2022; 55(12): 2255-70.
[http://dx.doi.org/10.1016/j.immuni.2022.11.009] [PMID: 36516818]
[http://dx.doi.org/10.1016/j.immuni.2022.11.009] [PMID: 36516818]
[5]
Desai N, Federico L, Baker JF. Lifestyle, hormonal, and metabolic environmental risks for rheumatoid arthritis. Rheum Dis Clin North Am 2022; 48(4): 799-811.
[http://dx.doi.org/10.1016/j.rdc.2022.06.003] [PMID: 36332996]
[http://dx.doi.org/10.1016/j.rdc.2022.06.003] [PMID: 36332996]
[6]
Kerekes G, Nurmohamed MT, González-Gay MA, et al. Rheumatoid arthritis and metabolic syndrome. Nat Rev Rheumatol 2014; 10(11): 691-6.
[http://dx.doi.org/10.1038/nrrheum.2014.121] [PMID: 25090948]
[http://dx.doi.org/10.1038/nrrheum.2014.121] [PMID: 25090948]
[7]
Venetsanopoulou AI, Pelechas E, Voulgari PV, Drosos AA. The lipid paradox in rheumatoid arthritis: The dark horse of the augmented cardiovascular risk. Rheumatol Int 2020; 40(8): 1181-91.
[http://dx.doi.org/10.1007/s00296-020-04616-2] [PMID: 32524301]
[http://dx.doi.org/10.1007/s00296-020-04616-2] [PMID: 32524301]
[8]
Quevedo-Abeledo JC, Sánchez-Pérez H, Tejera-Segura B, et al. Higher prevalence and degree of insulin resistance in patients with rheumatoid arthritis than in patients with systemic lupus erythematosus. J Rheumatol 2021; 48(3): 339-47.
[http://dx.doi.org/10.3899/jrheum.200435] [PMID: 32541071]
[http://dx.doi.org/10.3899/jrheum.200435] [PMID: 32541071]
[9]
Cai W, Yu Y, Zong S, Wei F. Metabolic reprogramming as a key regulator in the pathogenesis of rheumatoid arthritis. Inflamm Res 2020; 69(11): 1087-101.
[http://dx.doi.org/10.1007/s00011-020-01391-5] [PMID: 32797249]
[http://dx.doi.org/10.1007/s00011-020-01391-5] [PMID: 32797249]
[10]
Masoumi M, Hashemi N, Moadab F, et al. Immunometabolism dysfunction in the pathophysiology and treatment of rheumatoid arthritis. Curr Med Chem 2022; 30(27): 3119-136.
[http://dx.doi.org/10.2174/0929867329666220907151213] [PMID: 36082869]
[http://dx.doi.org/10.2174/0929867329666220907151213] [PMID: 36082869]
[11]
Romano S, Salustri E, Ruscitti P, Carubbi F, Penco M, Giacomelli R. Cardiovascular and metabolic comorbidities in rheumatoid arthritis. Curr Rheumatol Rep 2018; 20(12): 81.
[http://dx.doi.org/10.1007/s11926-018-0790-9] [PMID: 30397830]
[http://dx.doi.org/10.1007/s11926-018-0790-9] [PMID: 30397830]
[12]
Santos-Moreno P, Rodríguez-Vargas GS, Martínez S, Ibatá L, Rojas-Villarraga A. Metabolic abnormalities, cardiovascular disease, and metabolic syndrome in adult rheumatoid arthritis patients: Current perspectives and clinical implications. Open Access Rheumatol 2022; 14: 255-67.
[http://dx.doi.org/10.2147/OARRR.S285407] [PMID: 36388145]
[http://dx.doi.org/10.2147/OARRR.S285407] [PMID: 36388145]
[13]
Manrique-Arija S, Mena-Vazquez N, Ureña I, et al. Cumulative inflammatory burden and obesity as determinants of insulin resistance in patients with established rheumatoid arthritis: Cross-sectional study. BMJ Open 2021; 11(2): e044749.
[http://dx.doi.org/10.1136/bmjopen-2020-044749] [PMID: 33563625]
[http://dx.doi.org/10.1136/bmjopen-2020-044749] [PMID: 33563625]
[14]
Ye L, Zhang X, Wu H, et al. Insulin resistance and adverse lipid profile in untreated very early rheumatoid arthritis patients: A single-center, cross-sectional study in China. Arch Rheumatol 2022; 37(4): 593-602.
[http://dx.doi.org/10.46497/ArchRheumatol.2022.9117] [PMID: 36879573]
[http://dx.doi.org/10.46497/ArchRheumatol.2022.9117] [PMID: 36879573]
[15]
Diaz-Rubio GI, Corona-Meraz FI, Madrigal-Ruiz PM, et al. CCR2/CCL2 and CMKLR1/RvE1 chemokines system levels are associated with insulin resistance in rheumatoid arthritis. PLoS One 2021; 16(1): e0246054.
[http://dx.doi.org/10.1371/journal.pone.0246054] [PMID: 33508012]
[http://dx.doi.org/10.1371/journal.pone.0246054] [PMID: 33508012]
[16]
Guin A, Sinhamahapatra P, Misra S, Mazumder CSR, Chatterjee S, Ghosh A. Incidence and effect of insulin resistance on progression of atherosclerosis in rheumatoid arthritis patients of long disease duration. Biomed J 2019; 42(6): 394-402.
[http://dx.doi.org/10.1016/j.bj.2019.01.007] [PMID: 31948603]
[http://dx.doi.org/10.1016/j.bj.2019.01.007] [PMID: 31948603]
[17]
Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F. The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord 2008; 6(4): 299-304.
[http://dx.doi.org/10.1089/met.2008.0034] [PMID: 19067533]
[http://dx.doi.org/10.1089/met.2008.0034] [PMID: 19067533]
[18]
Tao LC, Xu J, Wang T, Hua F, Li JJ. Triglyceride-glucose index as a marker in cardiovascular diseases: Landscape and limitations. Cardiovasc Diabetol 2022; 21(1): 68.
[http://dx.doi.org/10.1186/s12933-022-01511-x] [PMID: 35524263]
[http://dx.doi.org/10.1186/s12933-022-01511-x] [PMID: 35524263]
[19]
Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62(9): 2569-81.
[http://dx.doi.org/10.1002/art.27584] [PMID: 20872595]
[http://dx.doi.org/10.1002/art.27584] [PMID: 20872595]
[20]
Ozisler C, Ates A, Karaaslan Y, et al. Clinical significance of aortic stiffness, carotid intima-media thickness and serum osteoprotegerin level in rheumatoid arthritis patients. Egypt Rheumatol 2019; 41(2): 111-5.
[http://dx.doi.org/10.1016/j.ejr.2018.07.002]
[http://dx.doi.org/10.1016/j.ejr.2018.07.002]
[21]
Prevoo MLL, Van’T HMA, Kuper HH, Van Leeuwen MA, Van De Putte LBA, Van Riel PLCM. Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38(1): 44-8.
[http://dx.doi.org/10.1002/art.1780380107] [PMID: 7818570]
[http://dx.doi.org/10.1002/art.1780380107] [PMID: 7818570]
[22]
Touboul PJ, Hennerici MG, Meairs S, et al. Mannheim intima-media thickness consensus. Cerebrovasc Dis 2004; 18(4): 346-9.
[http://dx.doi.org/10.1159/000081812] [PMID: 15523176]
[http://dx.doi.org/10.1159/000081812] [PMID: 15523176]
[23]
Kavurt S, Uzlu SE, Bas AY, et al. Can the triglyceride-glucose index predict insulin resistance in LGA newborns? J Perinatol 2022; 43: 1119-24.
[http://dx.doi.org/10.1038/s41372-022-01586-0] [PMID: 36564472]
[http://dx.doi.org/10.1038/s41372-022-01586-0] [PMID: 36564472]
[24]
Reckziegel MB, Nepomuceno P, Machado T, et al. The triglyceride-glucose index as an indicator of insulin resistance and cardiometabolic risk in Brazilian adolescents. Arch Endocrinol Metab 2023; 67(2): 153-61.
[http://dx.doi.org/10.20945/2359-3997000000506] [PMID: 36651702]
[http://dx.doi.org/10.20945/2359-3997000000506] [PMID: 36651702]
[25]
Jog KS, Eagappan S, Santharam RK, Subbiah S. Comparison of novel biomarkers of insulin resistance with homeostasis model assessment of insulin resistance, its correlation to metabolic syndrome in south indian population and proposition of population specific cutoffs for these indices. Cureus 2023; 15(1): e33653.
[http://dx.doi.org/10.7759/cureus.33653] [PMID: 36788883]
[http://dx.doi.org/10.7759/cureus.33653] [PMID: 36788883]
[26]
Luo P, Cao Y, Li P, et al. TyG index performs better than homa-ir in chinese type 2 diabetes mellitus with a BMI < 35 kg/m2: A hyperglycemic clamp validated study. Medicina 2022; 58(7): 876.
[http://dx.doi.org/10.3390/medicina58070876] [PMID: 35888595]
[http://dx.doi.org/10.3390/medicina58070876] [PMID: 35888595]
[27]
Zheng Y, Yin G, Chen F, Lin L, Chen Y. Evaluation of triglyceride glucose index and homeostasis model of insulin resistance in patients with polycystic ovary syndrome. Int J Womens Health 2022; 14: 1821-9.
[http://dx.doi.org/10.2147/IJWH.S387942] [PMID: 36582617]
[http://dx.doi.org/10.2147/IJWH.S387942] [PMID: 36582617]
[28]
Son DH, Lee HS, Lee YJ, Lee JH, Han JH. Comparison of triglyceride-glucose index and HOMA-IR for predicting prevalence and incidence of metabolic syndrome. Nutr Metab Cardiovasc Dis 2022; 32(3): 596-604.
[http://dx.doi.org/10.1016/j.numecd.2021.11.017] [PMID: 35090800]
[http://dx.doi.org/10.1016/j.numecd.2021.11.017] [PMID: 35090800]
[29]
Jin M, Lv P, Liang H, et al. Association of triglyceride-glucose index with major depressive disorder: A cross-sectional study. Medicine 2023; 102(24): e34058.
[http://dx.doi.org/10.1097/MD.0000000000034058] [PMID: 37327285]
[http://dx.doi.org/10.1097/MD.0000000000034058] [PMID: 37327285]
[30]
Zhao Y, Yang X, Wu Y, et al. Association of triglyceride–glucose index and its 6-year change with risk of hypertension: A prospective cohort study. Nutr Metab Cardiovasc Dis 2023; 33(3): 568-76.
[http://dx.doi.org/10.1016/j.numecd.2022.12.001] [PMID: 36642606]
[http://dx.doi.org/10.1016/j.numecd.2022.12.001] [PMID: 36642606]
[31]
Muhammad IF, Bao X, Nilsson PM, Zaigham S. Triglyceride-glucose (TyG) index is a predictor of arterial stiffness, incidence of diabetes, cardiovascular disease, and all-cause and cardiovascular mortality: A longitudinal two-cohort analysis. Front Cardiovasc Med 2023; 9: 1035105.
[http://dx.doi.org/10.3389/fcvm.2022.1035105] [PMID: 36684574]
[http://dx.doi.org/10.3389/fcvm.2022.1035105] [PMID: 36684574]
[32]
Liu F, Ling Q, Xie S, et al. Association between triglyceride glucose index and arterial stiffness and coronary artery calcification: A systematic review and exposure-effect meta-analysis. Cardiovasc Diabetol 2023; 22(1): 111.
[http://dx.doi.org/10.1186/s12933-023-01819-2] [PMID: 37179288]
[http://dx.doi.org/10.1186/s12933-023-01819-2] [PMID: 37179288]
[33]
Pei H, Li S, Su X, Lu Y, Wang Z, Wu S. Association between triglyceride glucose index and sleep disorders: Results from the NHANES 2005–2008. BMC Psychiatry 2023; 23(1): 156.
[http://dx.doi.org/10.1186/s12888-022-04434-9] [PMID: 36899383]
[http://dx.doi.org/10.1186/s12888-022-04434-9] [PMID: 36899383]
[34]
Contreras-Haro B, Hernandez-Gonzalez SO, Gonzalez-Lopez L, et al. Fasting triglycerides and glucose index: A useful screening test for assessing insulin resistance in patients diagnosed with rheumatoid arthritis and systemic lupus erythematosus. Diabetol Metab Syndr 2019; 11(1): 95.
[http://dx.doi.org/10.1186/s13098-019-0495-x] [PMID: 31788032]
[http://dx.doi.org/10.1186/s13098-019-0495-x] [PMID: 31788032]
[35]
Costa NT, Iriyoda VTM, Kallaur AP, et al. Influence of insulin resistance and TNF- α on the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis. Oxid Med Cell Longev 2016; 2016: 1-9.
[http://dx.doi.org/10.1155/2016/8962763] [PMID: 27340510]
[http://dx.doi.org/10.1155/2016/8962763] [PMID: 27340510]
[36]
Bellan M, Bor S, Gibbin A, et al. Inflammatory markers predict insulin sensitivity in active rheumatoid arthritis but not in psoriatic arthritis. Reumatismo 2018; 70(4): 232-40.
[http://dx.doi.org/10.4081/reumatismo.2018.1061] [PMID: 30570241]
[http://dx.doi.org/10.4081/reumatismo.2018.1061] [PMID: 30570241]
[37]
Gallagher L, Cregan S, Biniecka M, et al. Insulin-resistant pathways are associated with disease activity in rheumatoid arthritis and are subject to disease modification through metabolic reprogramming: A potential novel therapeutic approach. Arthritis Rheumatol 2020; 72(6): 896-902.
[http://dx.doi.org/10.1002/art.41190] [PMID: 31840936]
[http://dx.doi.org/10.1002/art.41190] [PMID: 31840936]
[38]
Masuko K. Angiopoietin-like 4: A molecular link between insulin resistance and rheumatoid arthritis. J Orthop Res 2017; 35(5): 939-43.
[http://dx.doi.org/10.1002/jor.23507] [PMID: 28004425]
[http://dx.doi.org/10.1002/jor.23507] [PMID: 28004425]
[39]
Wei Y, Xia N, Zhang W, et al. Serum retinol-binding protein 4 is associated with insulin resistance in patients with early and untreated rheumatoid arthritis. Joint Bone Spine 2019; 86(3): 335-41.
[http://dx.doi.org/10.1016/j.jbspin.2018.07.002] [PMID: 30025962]
[http://dx.doi.org/10.1016/j.jbspin.2018.07.002] [PMID: 30025962]
[40]
Corrado A, Colia R, Rotondo C, Sanpaolo E, Cantatore FP. Changes in serum adipokines profile and insulin resistance in patients with rheumatoid arthritis treated with anti-TNF- α. Curr Med Res Opin 2019; 35(12): 2197-205.
[http://dx.doi.org/10.1080/03007995.2019.1654988] [PMID: 31397188]
[http://dx.doi.org/10.1080/03007995.2019.1654988] [PMID: 31397188]
[41]
van den Oever IAM, Baniaamam M, Simsek S, et al. The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis. Rheumatol Int 2021; 41(2): 319-28.
[http://dx.doi.org/10.1007/s00296-020-04666-6] [PMID: 32776224]
[http://dx.doi.org/10.1007/s00296-020-04666-6] [PMID: 32776224]
[42]
Wang CR, Tsai HW. Immediate-release tofacitinib reduces insulin resistance in non-diabetic active rheumatoid arthritis patients: A single-center retrospective study. World J Diabetes 2022; 13(6): 454-65.
[http://dx.doi.org/10.4239/wjd.v13.i6.454] [PMID: 35800413]
[http://dx.doi.org/10.4239/wjd.v13.i6.454] [PMID: 35800413]
[43]
Bissell LA, Erhayiem B, Fent G, et al. Carotid artery volumetric measures associate with clinical ten-year cardiovascular (CV) risk scores and individual traditional CV risk factors in rheumatoid arthritis; a carotid-MRI feasibility study. Arthritis Res Ther 2018; 20(1): 266.
[http://dx.doi.org/10.1186/s13075-018-1761-2] [PMID: 30509325]
[http://dx.doi.org/10.1186/s13075-018-1761-2] [PMID: 30509325]
[44]
Reiss AB, Silverman A, Khalfan M, et al. Accelerated atherosclerosis in rheumatoid arthritis: Mechanisms and treatment. Curr Pharm Des 2019; 25(9): 969-86.
[http://dx.doi.org/10.2174/1381612825666190430113212] [PMID: 31208307]
[http://dx.doi.org/10.2174/1381612825666190430113212] [PMID: 31208307]
[45]
Mangoni AA, Tommasi S, Sotgia S, et al. Asymmetric dimethylarginine: A key player in the pathophysiology of endothelial dysfunction, vascular inflammation and atherosclerosis in rheumatoid arthritis? Curr Pharm Des 2021; 27(18): 2131-40.
[http://dx.doi.org/10.2174/1381612827666210106144247] [PMID: 33413061]
[http://dx.doi.org/10.2174/1381612827666210106144247] [PMID: 33413061]
[46]
Yang M, Luo Y, Liu T, et al. The effect of puerarin on carotid intima-media thickness in patients with active rheumatoid arthritis: A randomized controlled trial. Clin Ther 2018; 40(10): 1752-1764.e1.
[http://dx.doi.org/10.1016/j.clinthera.2018.08.014] [PMID: 30245282]
[http://dx.doi.org/10.1016/j.clinthera.2018.08.014] [PMID: 30245282]
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