Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study

Abstract Background The question as to whether or not diabetes mellitus increases the risk of idiopathic pulmonary fibrosis (IPF) remains controversial. This study aimed to investigate the causal association between type 1 diabetes (T1D), type 2 diabetes (T2D), and IPF using Mendelian randomization...

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Main Authors: Quou Kang, Jing Ren, Jinpeng Cong, Wencheng Yu
Format: Article
Language:English
Published: BMC 2024-03-01
Series:BMC Pulmonary Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12890-024-02961-7
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author Quou Kang
Jing Ren
Jinpeng Cong
Wencheng Yu
author_facet Quou Kang
Jing Ren
Jinpeng Cong
Wencheng Yu
author_sort Quou Kang
collection DOAJ
description Abstract Background The question as to whether or not diabetes mellitus increases the risk of idiopathic pulmonary fibrosis (IPF) remains controversial. This study aimed to investigate the causal association between type 1 diabetes (T1D), type 2 diabetes (T2D), and IPF using Mendelian randomization (MR) analysis. Methods We used two-sample univariate and multivariate MR (MVMR) analyses to investigate the causal relationship between T1D or T2D and IPF. We obtained genome-wide association study (GWAS) data for T1D and T2D from the European Bioinformatics Institute, comprising 29,652 T1D samples and 101,101 T1D single nucleotide polymorphisms (SNPs) and 655,666 T2D samples and 5,030,727 T2D SNPs. We also used IPF GWAS data from the FinnGen Biobank comprising 198,014 IPF samples and 16,380,413 IPF SNPs. All cases and controls in these datasets were derived exclusively from European populations. In the univariate MR analysis, we employed inverse variance-weighted (IVW), weighted median (WM), and MR-Egger regression methods. For the MVMR analysis, we used the multivariate IVW method primarily, and supplemented it with multivariate MR-Egger and multivariate MR- least absolute shrinkage and selection operator methods. Heterogeneity tests were conducted using the MR-IVW and MR-Egger regression methods, whereas pleiotropic effects were assessed using the MR-Egger intercept. The results of MR and sensitivity analyses were visualized using forest, scatter, leave-one-out, and funnel plots. Results Univariate MR revealed a significant causal relationship between T1D and IPF (OR = 1.118, 95% CI = 1.021–1.225, P = 0.016); however, no significant causal relationship was found between T2D and IPF (OR = 0.911, 95% CI = 0.796–1.043, P = 0.178). MVMR analysis further confirmed a causal association between T1D and IPF (OR = 1.133, 95% CI = 1.011–1.270, P = 0.032), but no causal relationship between T2D and IPF (OR = 1.009, 95% CI = 0.790–1.288, P = 0.950). Sensitivity analysis results validated the stability and reliability of our findings. Conclusion Univariate and multivariate analyses demonstrated a causal relationship between T1D and IPF, whereas no evidence was found to support a causal relationship between T2D and IPF. Therefore, in clinical practice, patients with T1D should undergo lung imaging for early detection of IPF.
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spelling doaj.art-c29cddc79d1144be859d7efe9b2442a82024-03-24T12:09:20ZengBMCBMC Pulmonary Medicine1471-24662024-03-0124111110.1186/s12890-024-02961-7Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization studyQuou Kang0Jing Ren1Jinpeng Cong2Wencheng Yu3Department of Pulmonary and Critical Care Medicine, The affiliated hospital of Qingdao University, Qingdao UniversityDepartment of Pulmonary and Critical Care Medicine, The affiliated hospital of Qingdao University, Qingdao UniversityDepartment of Pulmonary and Critical Care Medicine, The affiliated hospital of Qingdao University, Qingdao UniversityDepartment of Pulmonary and Critical Care Medicine, The affiliated hospital of Qingdao University, Qingdao UniversityAbstract Background The question as to whether or not diabetes mellitus increases the risk of idiopathic pulmonary fibrosis (IPF) remains controversial. This study aimed to investigate the causal association between type 1 diabetes (T1D), type 2 diabetes (T2D), and IPF using Mendelian randomization (MR) analysis. Methods We used two-sample univariate and multivariate MR (MVMR) analyses to investigate the causal relationship between T1D or T2D and IPF. We obtained genome-wide association study (GWAS) data for T1D and T2D from the European Bioinformatics Institute, comprising 29,652 T1D samples and 101,101 T1D single nucleotide polymorphisms (SNPs) and 655,666 T2D samples and 5,030,727 T2D SNPs. We also used IPF GWAS data from the FinnGen Biobank comprising 198,014 IPF samples and 16,380,413 IPF SNPs. All cases and controls in these datasets were derived exclusively from European populations. In the univariate MR analysis, we employed inverse variance-weighted (IVW), weighted median (WM), and MR-Egger regression methods. For the MVMR analysis, we used the multivariate IVW method primarily, and supplemented it with multivariate MR-Egger and multivariate MR- least absolute shrinkage and selection operator methods. Heterogeneity tests were conducted using the MR-IVW and MR-Egger regression methods, whereas pleiotropic effects were assessed using the MR-Egger intercept. The results of MR and sensitivity analyses were visualized using forest, scatter, leave-one-out, and funnel plots. Results Univariate MR revealed a significant causal relationship between T1D and IPF (OR = 1.118, 95% CI = 1.021–1.225, P = 0.016); however, no significant causal relationship was found between T2D and IPF (OR = 0.911, 95% CI = 0.796–1.043, P = 0.178). MVMR analysis further confirmed a causal association between T1D and IPF (OR = 1.133, 95% CI = 1.011–1.270, P = 0.032), but no causal relationship between T2D and IPF (OR = 1.009, 95% CI = 0.790–1.288, P = 0.950). Sensitivity analysis results validated the stability and reliability of our findings. Conclusion Univariate and multivariate analyses demonstrated a causal relationship between T1D and IPF, whereas no evidence was found to support a causal relationship between T2D and IPF. Therefore, in clinical practice, patients with T1D should undergo lung imaging for early detection of IPF.https://doi.org/10.1186/s12890-024-02961-7Idiopathic pulmonary fibrosisDiabetes mellitusType 1 diabetesType 2 diabetesMendelian randomizationHyperglycemia
spellingShingle Quou Kang
Jing Ren
Jinpeng Cong
Wencheng Yu
Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study
BMC Pulmonary Medicine
Idiopathic pulmonary fibrosis
Diabetes mellitus
Type 1 diabetes
Type 2 diabetes
Mendelian randomization
Hyperglycemia
title Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study
title_full Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study
title_fullStr Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study
title_full_unstemmed Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study
title_short Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study
title_sort diabetes mellitus and idiopathic pulmonary fibrosis a mendelian randomization study
topic Idiopathic pulmonary fibrosis
Diabetes mellitus
Type 1 diabetes
Type 2 diabetes
Mendelian randomization
Hyperglycemia
url https://doi.org/10.1186/s12890-024-02961-7
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