Impact of disease activity on impaired glucose metabolism in patients with rheumatoid arthritis

Gorica G Ristić; Vesna Subota; Dejana Stanisavljević; Danilo Vojvodić; Arsen D Ristić; Branislava Glišić; Milan Petronijević; Dušan Z Stefanović

doi:10.1186/s13075-021-02476-0

Impact of disease activity on impaired glucose metabolism in patients with rheumatoid arthritis

Arthritis Res Ther. 2021 Mar 26;23(1):95. doi: 10.1186/s13075-021-02476-0.

Authors

Gorica G Ristić¹, Vesna Subota², Dejana Stanisavljević³, Danilo Vojvodić⁴, Arsen D Ristić⁵, Branislava Glišić⁶, Milan Petronijević⁶, Dušan Z Stefanović⁶

Affiliations

¹ Department of Rheumatology and Clinical Immunology of the Military Medical Academy and Medical Faculty of the Military Medical Academy, University of Defense in Belgrade, Crnotravska 17, Belgrade, 11000, Serbia. goricaris@eunet.rs.
² Institute of Medical Biochemistry of the Military Medical Academy and Medical Faculty of the Military Medical Academy, University of Defense in Belgrade, Belgrade, Serbia.
³ Institute of Medical Statistics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
⁴ Institute for Medical Research of the Military Medical Academy and Medical Faculty of the Military Medical Academy, University of Defense in Belgrade, Belgrade, Serbia.
⁵ Department of Cardiology of the University Clinical Centre of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
⁶ Department of Rheumatology and Clinical Immunology of the Military Medical Academy and Medical Faculty of the Military Medical Academy, University of Defense in Belgrade, Crnotravska 17, Belgrade, 11000, Serbia.

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 (R²), 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.

Keywords: Insulin resistance; Matrix metalloproteinase-3; Rheumatoid arthritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid* / diagnosis
Biomarkers
Blood Sedimentation
C-Reactive Protein / analysis
Glucose
Humans
Insulin Resistance*
Risk Factors
Severity of Illness Index

Substances

Biomarkers
C-Reactive Protein
Glucose