Glucose as a Potential Key to Fuel Inflammation in Rheumatoid Arthritis

Masuko, Kayo

doi:10.3390/nu14112349

Cited by 9 publications

(4 citation statements)

References 77 publications

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“…45 Second, the persistence of hyperglycemia may promote the formation of advanced glycation end products, which have antigenicity and induce autoimmune reactions. 46 To our knowledge, this study is the first prospective cohort study to explore the direct influence of MetS on the incident RA. Our study found that participants with MetS had a higher risk of developing RA than non-MetS participants, and the risk of RA increased with increasing MetS components.…”

Section: Discussionmentioning

confidence: 94%

Metabolic Syndrome Is Associated With an Increased Risk of Rheumatoid Arthritis: A Prospective Cohort Study Including 369,065 Participants

Luo,

Xu,

et al. 2024

J Rheumatol

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ObjectiveTo explore the associations between metabolic syndrome (MetS) and its individual components and the risk of rheumatoid arthritis (RA).MethodsA total of 369,065 individuals were included in the present study based on the UK Biobank. Multivariable Cox proportional hazards regression models were applied to estimate the associations between MetS and its individual components and the risk of RA. Mediation analysis was performed to further assess the potential mediating role of C-reactive protein (CRP) in the relationship between MetS and RA.ResultsDuring a median follow-up period of 12.04 years, a total of 4901 incident RA cases were documented. MetS (hazard ratio [HR] 1.22, 95% CI 1.14-1.30) and 4 of its 5 components (elevated waist circumference [WC; HR 1.21, 95% CI 1.12-1.32], elevated triglyceride [TG] level [HR 1.12, 95% CI 1.05-1.19], reduced high-density lipoprotein cholesterol [HDL-C] level [HR 1.31, 95% CI 1.23-1.39], and hyperglycemia [HR 1.15, 95% CI 1.05-1.25]) were associated with an increased risk of RA. In addition, the risk of RA increased as the number of diagnosed MetS components increased, with the highest risk in participants with all 5 components. Mediation analysis showed that CRP might mediate the association between MetS and RA, accounting for 9.27% of the total effect.ConclusionThese findings indicated positive associations between MetS and 4 of its components (WC, TG, HDL-C, and hyperglycemia) and the risk of RA, highlighting the importance of MetS management in the prevention of RA.

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Section: Discussionmentioning

confidence: 94%

Metabolic Syndrome Is Associated With an Increased Risk of Rheumatoid Arthritis: A Prospective Cohort Study Including 369,065 Participants

Luo,

Xu,

et al. 2024

J Rheumatol

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“…Uric acid crystals activated NLRP3 via the AMPK-mTOR-ROS-TXNIP and TLR/NF-jB pathway [86,132,133], while cholesterol crystals depended on both NF-jB and Nrf2 to activate NLRP3 [134,135]. Glycometabolism-derived DAMPs, such as glucose and its precursor-AGEsare involved in the progression of T1D, RA, and SLE by driving pro-inflammatory cytokines (e.g., TNF-a, IL-6, and IL-1b) [136][137][138][139][140] and perpetuating chronic inflammation via PI3K/Akt pathway and NF-kB signaling [141][142][143]. They may also drive disease progression by affecting epigenetic modifications and causing oxidative stress [144,145].…”

Section: Metabolite-derived Damps and Autoimmune Diseasesmentioning

confidence: 99%

“…[79,82,83,84,85,86,136,137,138,139,140,141,142,143,144,145,162,163,164,165,166,167,168,169,170,171,172,173,174] T1D, RA, SLE [80,81,95,96,97,98,99,100,101,136,137, 138,139,140,141,142,143,144,145,149,150] [106,107,108,109,110,111,112,113,159,160,161] Uric acid crystalNLRP3, TRPV4 Gout, T1D, RA[105,114,115,116,117,118,119,120,121,132,133] …”

mentioning

confidence: 99%

Metabolite‐derived damage‐associated molecular patterns in immunological diseases

Kang

et al. 2023

The FEBS Journal

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Damage‐associated molecular patterns (DAMPs) are typically derived from the endogenous elements of necrosis cells and can trigger inflammatory responses by activating DAMPs‐sensing receptors on immune cells. Failure to clear DAMPs may lead to persistent inflammation, thereby contributing to the pathogenesis of immunological diseases. This review focuses on a newly recognized class of DAMPs derived from lipid, glucose, nucleotide, and amino acid metabolic pathways, which are then termed as metabolite‐derived DAMPs. This review summarizes the reported molecular mechanisms of these metabolite‐derived DAMPs in exacerbating inflammation responses, which may attribute to the pathology of certain types of immunological diseases. Additionally, this review also highlights both direct and indirect clinical interventions that have been explored to mitigate the pathological effects of these DAMPs. By summarizing our current understanding of metabolite‐derived DAMPs, this review aims to inspire future thoughts and endeavors on targeted medicinal interventions and the development of therapies for immunological diseases.

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“…Diabetes mellitus (DM) is a metabolic disorder characterized by abnormal glucose metabolism, with glycated hemoglobin (HbA1c) serving as a crucial marker for long-term glucose control in individuals with diabetes [6]. Emerging evidence suggests a close link between DM and RA, as both conditions share common pathophysiological features, such as chronic in ammation and metabolic dysregulation [7][8][9][10]. Numerous studies have reported a relationship between RA and DM incidence; however, the risk of RA in patients with established DM has been less investigated and yielded con icting results.…”

Section: Introductionmentioning

confidence: 99%

Effect of Higher Glycated Hemoglobin (HbA1c) Levels on rheumatoid arthritis Risk:A Mendelian Randomization Study

Liu

Zhang

Deng

et al. 2023

Preprint

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Introduction：Published studies have suggested a potential association between diabetes mellitus (DM) and RA, with glycated hemoglobin (HbA1c) serving as an important biomarker for DM. The purpose of this study was to investigate the causal relationship between HbA1c levels and RA risk using Mendelian randomization (MR) analysis. methods：A two-sample Mendelian randomization (MR) study was conducted using genetic variants as instrumental variables (IVs) related to HbA1c. Summary statistics from genome-wide association studies (GWAS) were obtained from the publicly accessible Integrative Epidemiology Unit (IEU) OpenGWAS database. A systematic selection process was employed to identify high-quality instrumental single-nucleotide polymorphisms (SNPs) strongly associated with the exposure. Various MR methodologies, such as inverse-variance weighted (IVW) and MR-Egger, were implemented to determine causal effects. The MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis were used to evaluate horizontal pleiotropy, heterogeneities, and stability of the association. Odds ratios (OR) and 95% confidence intervals (CI) were computed. Results：A total of 9 SNPs were identified as final IVs. The MR analysis demonstrated a significant causal relationship between elevated HbA1c levels and an increased risk of seronegative RA [odds ratio (OR) = 1.358, 95% confidence interval (CI), 1.044-1.767]. However, no significant evidence of a causal relationship was observed between HbA1c and seropositive RA [OR = 1.033, 95% CI, 0.850-1.257] or overall RA [OR = 1.093, 95% CI, 0.935-1.278]. Sensitivity analyses supported the robustness of the findings, with no significant evidence of heterogeneity or bias and no potential SNPs affecting the causal link. Conclusions:This study provides evidence of a causal relationship between HbA1c levels and seropositive RA risk, emphasizing the importance of closely monitoring and managing HbA1c levels in patients. Further research is needed to elucidate shared pathophysiological mechanisms between DM and RA, which may lead to novel therapeutic strategies.

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Glucose as a Potential Key to Fuel Inflammation in Rheumatoid Arthritis

Cited by 9 publications

References 77 publications

Metabolic Syndrome Is Associated With an Increased Risk of Rheumatoid Arthritis: A Prospective Cohort Study Including 369,065 Participants

Metabolic Syndrome Is Associated With an Increased Risk of Rheumatoid Arthritis: A Prospective Cohort Study Including 369,065 Participants

Metabolite‐derived damage‐associated molecular patterns in immunological diseases

Effect of Higher Glycated Hemoglobin (HbA1c) Levels on rheumatoid arthritis Risk:A Mendelian Randomization Study

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