Impact of Disease Activity on Impaired Glucose Metabolism in Patients with Rheumatoid Arthritis

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2021 Mar 27

PMID 33771189

Citations 6

Authors

Gorica G Ristic

Vesna Subota

Dejana Stanisavljevic

Danilo Vojvodic

Arsen D Ristic

Branislava Glisic

Milan Petronijevic

Dusan Z Stefanovic

Affiliations

Soon will be listed here.

Abstract

Objective: To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3).

Methods: This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of β-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses.

Results: RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient's global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (β = 0.206, P = 0.014; β = 0.192, P = 0.009; β = 0.121, P = 0.005; β = 0.148, P = 0.007; β = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (β = 0.090, P = 0.022; β = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2-2.5) vs. 1.2 (0.8-1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9-1.9) vs. 1.2 (0.8-1.4), P = 0.375].

Conclusions: RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors.

Citing Articles

Levamisole Ameliorates Rheumatoid Arthritis by Downregulating the PI3K/Akt Pathway in SD Rats.

Guo M, Yu X, Yang Z, Zheng H, Zhang J, Wang J Pharmaceuticals (Basel). 2024; 17(11).

PMID: 39598415 PMC: 11597538. DOI: 10.3390/ph17111504.

Diabetes and Osteoarthritis: Exploring the Interactions and Therapeutic Implications of Insulin, Metformin, and GLP-1-Based Interventions.

Halabitska I, Babinets L, Oksenych V, Kamyshnyi O Biomedicines. 2024; 12(8).

PMID: 39200096 PMC: 11351146. DOI: 10.3390/biomedicines12081630.

Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case-control study.

Moellering D, Smith-Johnston K, Kelley C, Sammy M, Benedict J, Brock G Arthritis Res Ther. 2023; 25(1):85.

PMID: 37210569 PMC: 10199606. DOI: 10.1186/s13075-023-03065-z.

Identification and validation of metabolism-related genes signature and immune infiltration landscape of rheumatoid arthritis based on machine learning.

Guo Z, Ma Y, Wang Y, Xiang H, Cui H, Fan Z Aging (Albany NY). 2023; 15(9):3807-3825.

PMID: 37166429 PMC: 10449312. DOI: 10.18632/aging.204714.

Repurposing antidiabetic drugs for rheumatoid arthritis: results from a two-sample Mendelian randomization study.

Qin C, Diaz-Gallo L, Tang B, Wang Y, Nguyen T, Harder A Eur J Epidemiol. 2023; 38(7):809-819.

PMID: 37052755 PMC: 10276071. DOI: 10.1007/s10654-023-01000-9.

References

Avina-Zubieta J, Thomas J, Sadatsafavi M, Lehman A, Lacaille D . Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012; 71(9):1524-9. DOI: 10.1136/annrheumdis-2011-200726. View

Kumeda Y, Inaba M, Goto H, Nagata M, Henmi Y, Furumitsu Y . Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis. Arthritis Rheum. 2002; 46(6):1489-97. DOI: 10.1002/art.10269. View

van Halm V, Peters M, Voskuyl A, Boers M, Lems W, Visser M . Rheumatoid arthritis versus diabetes as a risk factor for cardiovascular disease: a cross-sectional study, the CARRE Investigation. Ann Rheum Dis. 2008; 68(9):1395-400. DOI: 10.1136/ard.2008.094151. View

Giles J, Danielides S, Szklo M, Post W, Blumenthal R, Petri M . Insulin resistance in rheumatoid arthritis: disease-related indicators and associations with the presence and progression of subclinical atherosclerosis. Arthritis Rheumatol. 2014; 67(3):626-36. PMC: 6058692. DOI: 10.1002/art.38986. View

Svenson K, Pollare T, Lithell H, Hallgren R . Impaired glucose handling in active rheumatoid arthritis: relationship to peripheral insulin resistance. Metabolism. 1988; 37(2):125-30. DOI: 10.1016/s0026-0495(98)90005-1. View

Festa A, DAgostino Jr R, Howard G, Mykkanen L, Tracy R, Haffner S . Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2000; 102(1):42-7. DOI: 10.1161/01.cir.102.1.42. View

Muniyappa R, Lee S, Chen H, Quon M . Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2007; 294(1):E15-26. DOI: 10.1152/ajpendo.00645.2007. View

Chung C, Oeser A, Solus J, Gebretsadik T, Shintani A, Avalos I . Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis Rheum. 2008; 58(7):2105-12. PMC: 2755593. DOI: 10.1002/art.23600. View

Levy J, Matthews D, Hermans M . Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998; 21(12):2191-2. DOI: 10.2337/diacare.21.12.2191. View

10.

Sattar N, McCarey D, Capell H, McInnes I . Explaining how "high-grade" systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation. 2003; 108(24):2957-63. DOI: 10.1161/01.CIR.0000099844.31524.05. View

11.

Wagenknecht L, Langefeld C, Scherzinger A, Norris J, Haffner S, Saad M . Insulin sensitivity, insulin secretion, and abdominal fat: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Diabetes. 2003; 52(10):2490-6. DOI: 10.2337/diabetes.52.10.2490. View

12.

Tejera-Segura B, Lopez-Mejias R, de Vera-Gonzalez A, Jimenez-Sosa A, Olmos J, Hernandez J . Relationship Between Insulin Sensitivity and β-Cell Secretion in Nondiabetic Subjects with Rheumatoid Arthritis. J Rheumatol. 2018; 46(3):229-236. DOI: 10.3899/jrheum.180198. View

13.

Peters M, van Halm V, Voskuyl A, Smulders Y, Boers M, Lems W . Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study. Arthritis Rheum. 2009; 61(11):1571-9. DOI: 10.1002/art.24836. View

14.

Lerner A, Neidhofer S, Reuter S, Matthias T . MMP3 is a reliable marker for disease activity, radiological monitoring, disease outcome predictability, and therapeutic response in rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2019; 32(4):550-562. DOI: 10.1016/j.berh.2019.01.006. View

15.

Shahin D, Eltoraby E, Mesbah A, Houssen M . Insulin resistance in early untreated rheumatoid arthritis patients. Clin Biochem. 2010; 43(7-8):661-5. DOI: 10.1016/j.clinbiochem.2010.01.012. View

16.

Ferraz-Amaro I, Garcia-Dopico J, Medina-Vega L, Gonzalez-Gay M, Diaz-Gonzalez F . Impaired beta cell function is present in nondiabetic rheumatoid arthritis patients. Arthritis Res Ther. 2013; 15(1):R17. PMC: 3672807. DOI: 10.1186/ar4149. View

17.

Choy E, Ganeshalingam K, Semb A, Szekanecz Z, Nurmohamed M . Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment. Rheumatology (Oxford). 2014; 53(12):2143-54. PMC: 4241890. DOI: 10.1093/rheumatology/keu224. View

18.

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

19.

Ristic G, Lepic T, Glisic B, Stanisavljevic D, Vojvodic D, Petronijevic M . Rheumatoid arthritis is an independent risk factor for increased carotid intima-media thickness: impact of anti-inflammatory treatment. Rheumatology (Oxford). 2010; 49(6):1076-81. DOI: 10.1093/rheumatology/kep456. View

20.

Hoes J, van der Goes M, van Raalte D, van der Zijl N, den Uyl D, Lems W . Glucose tolerance, insulin sensitivity and β-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids. Ann Rheum Dis. 2011; 70(11):1887-94. DOI: 10.1136/ard.2011.151464. View