Background Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung scarring. There is a known association between diabetes mellitus (DM) and IPF, but it is unclear whether a causal relationship exists between these traits. Objectives The objectives of this study are to examine causal relationships among DM, diabetes-associated traits and IPF using a Mendelian randomisation approach. Methods Two-sample MR approaches, including bidirectional inverse-variance weighted random effects and routine sensitivity models, used genetic variants identified from genome-wide association studies for type 1 diabetes (T1D), type 2 diabetes (T2D), glycated haemoglobin level (HbA1c), fasting insulin level and body mass index (BMI) to assess for causal effects of these traits on IPF. Further analyses using pleiotropy-robust and multivariable MR (MVMR) methods were additionally performed to account for trait complexity. Results Results did not suggest that either T1D (OR=1.00, 95% CI 0.93 to 1.07, p=0.90) or T2D (1.02, 0.93 to 1.11, p=0.69) are in the causal pathway of IPF. No effects were suggested of HbA1c (1.19, 0.63 to 2.22, p=0.59) or fasting insulin level (0.60, 0.31 to 1.15, p=0.12) on IPF, but potential effects of BMI on IPF were indicated (1.44, 1.12 to 1.85, p=4.00×10−3). Results were consistent in MVMR, although no independent effects of T2D (0.91, 0.68 to 1.21, p=0.51) or BMI (1.01, 0.94 to 1.09, p=0.82) on IPF were observed when modelled together. Conclusions This 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. Data are available upon reasonable request. Summary results for the GWAS of IPF susceptibility were requested through the collaborative genetic studies of idiopathic pulmonary fibrosis GitHub page: (). Summary data for all other GWAS studies were retrieved from GWAS catalog ().

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评估糖尿病和特发性肺纤维化之间的因果关系：一项孟德尔随机化研究


背景特发性肺纤维化 （IPF） 是一种进行性肺瘢痕形成的疾病。糖尿病 （DM） 和 IPF 之间存在已知的关联，但尚不清楚这些特征之间是否存在因果关系。目的 本研究的目的是使用孟德尔随机化方法检查 DM、糖尿病相关特征和 IPF 之间的因果关系。方法 双样本 MR 方法，包括双向逆方差加权随机效应和常规敏感性模型，使用从 1 型糖尿病 （T1D）、2 型糖尿病 （T2D）、糖化血红蛋白水平 （HbA1c）、空腹胰岛素水平和体重指数 （BMI） 的全基因组关联研究中鉴定的遗传变异来评估这些特征对 IPF 的因果影响。此外，还使用多效性稳健和多变量 MR （MVMR） 方法进行了进一步分析，以解释性状复杂性。结果 结果未表明 T1D （OR=1.00,95% CI 0.93 至 1.07，p=0.90） 或 T2D （1.02,0.93 至 1.11，p=0.69） 位于 IPF 的因果途径中。未表明 HbA1c （1.19， 0.63 至 2.22，p = 0.59） 或空腹胰岛素水平 （0.60， 0.31 至 1.15，p = 0.12） 对 IPF 有影响，但表明 BMI 对 IPF 的潜在影响 （1.44， 1.12 至 1.85，p = 4.00×10-3）。MVMR 的结果一致，尽管当一起建模时，没有观察到 T2D （0.91， 0.68 至 1.21， p=0.51） 或 BMI （1.01， 0.94 至 1.09，p=0.82） 对 IPF 的独立影响。结论 本研究表明 DM 和 IPF 不太可能有因果关系。相反，这种共病关系可能由共同的危险因素或治疗效果驱动。数据可根据合理要求提供。 通过特发性肺纤维化的协作遗传研究 GitHub 页面要求 IPF 易感性 GWAS 的总结结果：（）。所有其他 GWAS 研究的摘要数据均从 GWAS 目录 （） 中检索。