Mediation Analysis of Type 2 Diabetes Mellitus on the Relationship Between Air Pollution and Chronic Kidney Disease

Abstract Increasing evidence suggests associations between air pollution and elevated risks of chronic kidney disease (CKD). Besides, the link between air pollution and type 2 diabetes mellitus (T2DM) has been well documented mainly through systemic inflammation and insulin resistance. Given T2DM is a critical risk factor for CKD, and a high prevalence of DM is observed in patients with CKD, the interplay of air pollution, T2DM, and CKD warrants investigations. This study hypothesizes that T2DM mediates the temporal relationship between air pollution and CKD. This retrospective cohort study utilized data from the Adult Preventive Healthcare Services (APHS) Database and Taiwan’s National Health Insurance (NHI) claims, comprising 2,832,765 participants with ≥ 2 health checkups between 2012 and 2021 and without pre-existing CKD or T2DM prior to the first-time checkup (i.e., cohort entry). Exposure to six air pollutants (PM 2.5 , PM 10 , NO 2 , SO 2 , CO, and O 3 ) in a 3-year period prior to cohort entry was assessed using land-use regression integrated with machine learning algorithms. Causal mediation analysis was conducted to estimate natural direct and indirect effects of air pollution on CKD through incident T2DM. Indirect effects through incident T2DM were modest. Among pollutants with non-null indirect effects, the proportion mediated ranged from 6.33% to 9.20% (PM 10 : 6.33%; NO 2 : 9.20%; CO: 7.10%), whereas for PM 2.5 , SO 2 , and O 3 the indirect effects were approximately null and the proportion mediated was not reported. Further investigations on the potential pathways linking air pollution and CKD may help mitigate CKD risk. Graphical Abstract