Idiopathic pulmonary fibrosis and diabetes mellitus: a meta-analysis and systematic review

Bai, Le; Zhang, Li; Pan, Tingyu; Wang, Wei; Wang, Dian; Turner, C. H.; Zhou, Xianmei; He, Hailang

doi:10.1186/s12931-021-01760-6

Cited by 32 publications

(24 citation statements)

References 59 publications

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“… 24 25 There is an association between DM and ILD/IPF with an unknown mechanism. 26 Our study has shown that DM with end-organ damage increased RA-ILD mortality. Further study is needed to explore the pathophysiology linkage between DM and RA-ILD.…”

Section: Discussionmentioning

confidence: 57%

Analysis of risk factors of mortality in rheumatoid arthritis patients with interstitial lung disease: a nationwide, population-based cohort study in Taiwan

Chen

Lin

et al. 2022

RMD Open

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ObjectiveTo examine the risk and risk factors of mortality in patients with rheumatoid arthritis (RA) with interstitial lung disease (ILD).MethodsUsing the 1997–2013 Taiwanese National Health Insurance Research Database, we identified 32 289 incident patients with RA by using International Classification of Diseases, Ninth Revision codes from 2001 to 2013, and 214 patients developed ILD subsequently. We matched (1:10) RA-ILD with controls for sex, age, time of ILD diagnosis and disease duration. In addition, we conducted propensity score matching (PSM) (1:1) for selected comorbidities to choose RA-ILD patients and controls. Using the Cox proportional hazard model, we estimated the association of mortality with ILD for the two matched populations and assessed factors associated with mortality among 214 RA-ILD patients, shown as adjusted HRs (aHRs) with 95% CIs.ResultsIn the populations selected before and after PSM, we included 164 and 155 patients with RA-ILD and 1640 and 155 controls, respectively. ILD was associated with mortality in the population before PSM (aHR, 1.73; 95% CI 1.19 to 2.52) and in the PSM population (HR 4.38; 95% CI 2.03 to 9.43). Among 214 patients with RA-ILD, age (aHR 1.04; 95% CI 1.03 to 1.08), chronic obstructive pulmonary disease (COPD) (aHR 2.12; 95% CI 1.25 to 3.58), diabetes mellitus (DM) with end-organ damage and corticosteroid dose (prednisolone equivalent, mg/day) (aHR 1.09; 95% CI 1.07 to 1.11) were associated with mortality in RA-ILD.ConclusionThis population-based cohort study showed that ILD was associated with risk of mortality in patients with RA, and risk factors associated with mortality in patients with RA-ILD included age, COPD, DM with end-organ damage and average daily prednisolone dose.

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Section: Discussionmentioning

confidence: 57%

Analysis of risk factors of mortality in rheumatoid arthritis patients with interstitial lung disease: a nationwide, population-based cohort study in Taiwan

Chen

Lin

et al. 2022

RMD Open

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“…Therefore, the clinical effectiveness of MET in patients with PF should be combined with ongoing studies on PF-specific biomarkers ( Raghu et al, 2018 ). 3) PF may not be clinically isolated, often existing in combination with other diseases, and may be influenced by factors such as smoking, age, and sex of the patient, suggesting that confounding factors often influence these studies ( Bai et al, 2021 ). This may be the reason for some bias in the studies and the impact of the results.…”

Section: Discussionmentioning

confidence: 99%

“…Hyperglycemia causes inflammation and oxidative stress in the body, which are closely related to the core developmental mechanisms of PF, such as extracellular matrix (ECM) deposition, fibroblast/myofibroblast proliferation, and structural disruption of the lung tissue ( Willis & Borok, 2007 ). Similarly, in a meta-analysis, a significant increase in the prevalence of DM was demonstrated in patients with IPF compared with that in controls, suggesting a potential positive association between DM and the development of IPF ( Bai et al, 2021 ).…”

Section: Introductionmentioning

confidence: 93%

Effectiveness and mechanism of metformin in animal models of pulmonary fibrosis: A preclinical systematic review and meta-analysis

Xiao

Chen

et al. 2022

Front. Pharmacol.

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Background: Pulmonary fibrosis (PF) is a lung disease with no curative drug, characterized by a progressive decrease in lung function. Metformin (MET) is a hypoglycemic agent with the advantages of high safety and low cost and has been used in several in vivo trials to treat fibrotic diseases.Objective: This study aimed to explore the efficacy and safety of MET in treating PF and elaborate on its mechanism.Methods: Eight databases were searched for in vivo animal trials of MET for PF from the time of database creation until 1 March 2022. The risk of bias quality assessment of the included studies was conducted using SYRCLE’s risk of bias assessment. Pulmonary inflammation and fibrosis scores were the primary outcomes of this study. Hydroxyproline (HYP), type I collagen (collagen I), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), Smad, AMP-activated protein kinase (AMPK), and extracellular signal–regulated kinase (ERK) protein expression in lung tissues and animal mortality were secondary outcomes. Effect magnitudes were combined and calculated using Revman 5.3 and Stata 16.0 to assess the efficacy and safety of MET in animal models of PF. Inter-study heterogeneity was examined using the I2 or Q test, and publication bias was assessed using funnel plots and Egger’s test.Results: A total of 19 studies involving 368 animals were included, with a mean risk of bias of 5.9. The meta-analysis showed that MET significantly suppressed the level of inflammation and degree of PF in the lung tissue of the PF animal model. MET also reduced the content of HYP, collagen I, α-SMA, and TGF-β and phosphorylation levels of Smad2, Smad3, p-smad2/3/smad2/3, ERK1/2, and p-ERK1/2/ERK1/2 in lung tissues. MET also elevated AMPK/p-AMPK levels in lung tissues and significantly reduced animal mortality.Conclusion: The results of this study suggest that MET has a protective effect on lung tissues in PF animal models and may be a potential therapeutic candidate for PF treatment.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=327285, identifier CRD42022327285.

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“…The relatedness of IPF to diabetes is another finding worth discussion. There are several clinical studies including clinical meta analyses suggesting an association between IPF and diabetes [31][32][33][34] . Our computational study also indicates molecular relatedness of IPF to diabetes (Fig.…”

Section: Pre-clinical and Clinical Evidencementioning

confidence: 99%

Latent inter-organ mechanism of idiopathic pulmonary fibrosis unveiled by a generative computational approach

Kozawa

Tejima

Takagi

et al. 2023

Preprint

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Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease characterized by complex lung pathogenesis affecting approximately three million people worldwide. While the molecular and cellular details of the IPF mechanism is emerging, our current understanding is centered around the lung itself. On the other hand, many human diseases are the products of complex multi-organ interactions. Hence, we postulate that a dysfunctional crosstalk of the lung with other organs plays a causative role in the onset, progression and/or complications of IPF. In this study, we employed a generative computational approach to identify such inter-organ mechanism of IPF. The approach works as follows: 1) To find unexpected relatedness of IPF to other diseases of non-lung organs and to identify molecular features that define such relatedness, 2) To identify differentially expressed genes between the lung tissues of IPF vs. those of non-IPF pulmonary disease patients, 3) To detect ligand-receptor relationships across multiple organs and their upstream and downstream signaling pathways in 1) and 2), 4) To generate a map of the inter-organ IPF mechanism with the molecular and cellular resolution. This approach found unexpected molecular relatedness of IPF to neoplasm, diabetes, Alzheimer′s disease, obesity, atherosclerosis, and arteriosclerosis. Furthermore, as a potential mechanism underlying this relatedness, we uncovered a putative molecular crosstalk system across the lung and the liver. In this inter-organ system, a secreted protein, kininogen 1, from hepatocytes in the liver interacts with its receptor, bradykinin receptor B1 in the lung. This ligand-receptor interaction across the liver and the lung leads to the activation of calmodulin pathways in the lung, leading to the activation of interleukin 6 and phosphoenolpyruvate carboxykinase 1 pathway across these organs. Furthermore, we retrospectively identified several pre-clinical and clinical evidence supporting this inter-organ mechanism of IPF. In conclusion, such feedforward and feedback system across the lung and the liver provides a unique opportunity for the development of the treatment and/or diagnosis of IPF. Furthermore, the result illustrates a generative computational framework for machine-mediated synthesis of mechanisms that facilitates and complements the traditional experimental approaches in biomedical sciences.

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Idiopathic pulmonary fibrosis and diabetes mellitus: a meta-analysis and systematic review

Cited by 32 publications

References 59 publications

Analysis of risk factors of mortality in rheumatoid arthritis patients with interstitial lung disease: a nationwide, population-based cohort study in Taiwan

Analysis of risk factors of mortality in rheumatoid arthritis patients with interstitial lung disease: a nationwide, population-based cohort study in Taiwan

Effectiveness and mechanism of metformin in animal models of pulmonary fibrosis: A preclinical systematic review and meta-analysis

Latent inter-organ mechanism of idiopathic pulmonary fibrosis unveiled by a generative computational approach

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