Effects of Diabetes Mellitus and Glycemic Traits on COPD and Pulmonary Function Traits: Insights From Mendelian Randomization and NHANES

Purpose: This two-sample Mendelian randomization (MR) analysis and study based on the National Health and Nutrition Examination Survey (NHANES) aimed to evaluate the effects of diabetes mellitus and glycemic traits on chronic obstructive pulmonary disease (COPD) and pulmonary function traits. Patients and Methods: Utilizing a two-sample MR analysis and NHANES data (2007-2012), this study investigated the associations of diabetes and glycemic traits with COPD and pulmonary function traits. Exposures included type 1 (T1DM) and type 2 diabetes (T2DM), fasting glucose (FGlu), fasting insulin (FIns), glycated hemoglobin (HbA1c), and 2-hour glucose (2hGlu). Outcomes included COPD, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), the FEV1/FVC ratio, and peak expiratory flow (PEF). The MR analysis employed inverse variance weighted (IVW) and weighted median methods. Multivariate logistic regression and linear regression were used to evaluate the associations, adjusting for age, gender, race, body mass index (BMI), and blood cholesterol in the NHANES database. Results: MR analyses (IVW results) indicated significant causal relationships between T1DM and COPD, and FEV1/FVC ratio (OR = 1.023, 95% CI = 1.012 to 1.034, P < 0.0001; beta = -0.0075, 95% CI = -0.0122 to -0.0028, P = 0.0018, respectively). T2DM also exhibited significant causal associations with FVC and FEV1/FVC ratio (beta = -0.0330, 95% CI = -0.0448 to -0.0212, P < 0.0001; beta = 0.0172, 95% CI = 0.0065 to 0.0279, P = 0.0016). 2hGlu showed a significant causal relationship with FEV1/FVC ratio (beta = 0.0472, 95% CI = 0.0089 to 0.0856, P = 0.0159). A total of 389 participants were enrolled in this study (unweighted), with a weighted sample size of 6324845, based on the NHANES database. Multivariate logistic regression revealed no statistically significant association between diabetes, glycemic traits, and COPD. Multivariate linear regression indicated that a 2.7-fold increase in HbA1c levels was negatively correlated with declines in FEV1 (42.56%), FVC (34.92%), and PEF (37.77%). Conclusion: This study demonstrated the impact of diabetes and glycemic traits on COPD and lung function traits, highlighting important clinical implications.