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Updated: Jun 30, 2025
Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity
Published on: January 6, 2015
Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study
Quou Kang1,2, Jing Ren1,2, Jinpeng Cong1
1Department of Pulmonary and Critical Care Medicine, The affiliated hospital of Qingdao University, Qingdao University, Qingdao, China.
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.
Insights
Type 1 diabetes (T1D) causally increases the risk of idiopathic pulmonary fibrosis (IPF), but type 2 diabetes (T2D) does not. Early lung imaging is recommended for T1D patients to detect IPF.
Area of Science:
- Genetics and Epidemiology
- Pulmonology
- Endocrinology
Background:
- The relationship between diabetes mellitus and idiopathic pulmonary fibrosis (IPF) risk is debated.
- This study investigates the potential causal link between type 1 diabetes (T1D) and type 2 diabetes (T2D) with IPF.
Purpose of the Study:
- To determine if T1D or T2D causally influences the risk of developing IPF.
- Utilizing Mendelian randomization (MR) analysis for robust causal inference.
Main Methods:
- Employed two-sample univariate and multivariate Mendelian randomization (MR) analyses.
- Utilized large-scale genome-wide association study (GWAS) data for T1D, T2D, and IPF from European populations.
- Applied various MR methods (IVW, WM, MR-Egger) and sensitivity analyses to ensure result validity.
Main Results:
- Univariate and multivariate MR analyses revealed a significant causal association between T1D and IPF.
- No significant causal relationship was identified between T2D and IPF in either analysis.
- Sensitivity analyses confirmed the robustness and reliability of the findings.
Conclusions:
- A causal link exists between T1D and an increased risk of IPF.
- No evidence supports a causal relationship between T2D and IPF.
- Clinical guidelines should consider lung screening for early IPF detection in T1D patients.
