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Abstract

RationaleIdiopathic Pulmonary Fibrosis (IPF) is a disease of progressive lung scarring. There is a known association between IPF and diabetes mellitus (DM), but it is unclear whether this association is due to causal relationships between these traits. ObjectivesTo examine causal relationships between DM, diabetes-associated traits, and IPF using a Mendelian randomisation approach. MethodsFollowing a two-sample Mendelian randomisation (MR) approach, we used genetic variants identified from genome wide association studies (GWAS) for type 1 diabetes (T1D), type 2 diabetes (T2D), glycated haemoglobin level (HbA1c), fasting insulin level, and body mass index (BMI) to assess for evidence of causal effects of these traits on IPF risk. Further analyses using pleiotropy-robust and multivariable MR methods were performed to account for the inherent complexity of the traits being investigated. ResultsResults did not suggest that either T1D (OR = 1.00, 95% CI: 0.93-1.07, p = 0.902) or T2D (OR = 1.02, 95% CI: 0.93-1.11, p = 0.692) are in the causal pathway of IPF. No significant effects were suggested of HbA1c (OR = 1.19, 95% CI: 0.63-2.22, p = 0.592) or fasting insulin level (OR = 0.60, 95% CI: 0.31-1.15, p = 0.124) on IPF risk, but effects of BMI on IPF risk were indicated (OR = 1.44, 95% CI: 1.12-1.85, p = 0.004). ConclusionThis study suggests that DM and IPF are unlikely to be causally linked. This comorbid relationship may instead be driven by shared risk factors or treatment effects. Key messagesWhat is already known on this topic: Idiopathic pulmonary fibrosis is associated with diabetes mellitus epidemiologically, but it is unclear if these traits are linked by causal effects. What this study adds: Idiopathic pulmonary fibrosis and diabetes mellitus are unlikely to be causally linked, suggesting that shared environmental risk factors or treatment effects may drive this comorbid relationship. How this study might affect research, practice, or policy: Further research investigating the relationship between diabetes mellitus and idiopathic pulmonary fibrosis should focus on potential shared risk factors such as smoking, and treatment effects including corticosteroid use.

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