Potential Causal Relationship Between Chronic Obstructive Pulmonary Disease and Diabetes: A Bidirectional Two-Sample Mendelian Randomization Study.

Abstract

Purpose: Diabetes, particularly type 2 diabetes (T2D), is a common comorbidity that occurs at a higher frequency in chronic obstructive pulmonary disease (COPD) patients compared to the general population. The COPD-diabetes association is documented epidemiologically and experimentally. Potential mechanisms, including systemic inflammation and metabolic dysregulation, are discussed as plausible pathways. However, their causal relationship still needs to be confirmed.

Methods: We conducted a comprehensive bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the causal links between COPD and both type 1 diabetes (T1D) and T2D by using genome-wide association study (GWAS) summary statistics in European and Asian populations. By employing MR methods, the causal effect of diabetes on the risk of COPD as well as specific COPD-related clinical outcomes, including COPD with infections (COPD-I), pneumonia or pneumonia-derived septicaemia, chronic opportunistic infections, respiratory insufficiency, hospital admissions, and onset age (early or late) were explored.

Results: Forward MR analysis provided evidence consistent with a causal relationship between T2D and an increased risk of COPD in the European population (IVW odds ratio (OR): 1.002, 95% confidence interval (CI): 1.001-1.003, P = 0.001). This association appeared consistent with MR Egger analysis, yielding a similar result for European COPD patients (MR Egger OR: 1.108, 95% CI: 1.016 -1.208, P = 0.021). No statistically conclusive evidence of a causal relationship between diabetes and COPD was found in the Asian population. Besides, genetically determined T1D was identified as a risk factor for the incidence of COPD-I in the European-specific population (IVW OR: 1.017, 95% CI: 1.009-1.025, P < 0.001). The reverse MR analysis, exploring the effect of COPD on the risk of diabetes, did not achieve consistent results in either the European or Asian populations.

Conclusion: This study suggested a modest but statistically significant causal association between T2D and COPD in individuals of European ancestry. Further explorations are required to better understand the underlying mechanisms linking diabetes to COPD development.