Abstract
BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is common worldwide. Patients with T2DM often experience reduced lung function, but the relationship between the two conditions remains uncertain. This study employed Mendelian Randomization (MR) to explore the causal link between T2DM and lung function, and to identify the factors that mediate this relationship. METHODS: Genome-wide association study data were obtained from public databases. Four glycemic traits were considered exposures, whereas lung function was considered an outcome. Inverse Variance Weighting (IVW) was used to investigate causality, supplemented by MR-Egger and weighted medians methods. Multivariable MR (MVMR) analysis investigated whether T2DM had an independent impact on lung function. Mediation analysis was employed to examine potential mediating impacts. RESULTS: IVW revealed that T2DM was associated with decreased forced expiratory volume in 1s (FEV1) (p = 0.012) and Forced Vital Capacity (FVC) (p = 0.004). After adjusting for potential confounders, the effects of T2DM on FEV1 and FVC remained significant. Mediation analysis demonstrated that smoking and Systolic Blood Pressure (SBP) partially mediated the causal relationship between T2DM, and FEV1 and FVC. The proportions mediated by smoking, SBP, and both factors on FEV1 were 0.302, 0.412, and 0.418, respectively, while the proportion mediated by SBP on FVC was 0.594. CONCLUSIONS: This study validated the causal relationship between T2DM and decreased lung function, with smoking and SBP acting as mediators. This study provides a novel perspective on the occurrence and development mechanisms of reduced lung function as well as potential new targets for metabolic intervention in treatment.