Interaction effects of type 2 diabetes mellitus and air pollutants on white matter structures and cognitive function

Background and Objectives: Alterations in white matter (WM) integrity, which are linked to cognitive impairments, are influenced by both type 2 diabetes mellitus (T2DM) and air pollutants (APs). However, the interaction effects between the two factors on WM structures remain unclear. Our study aimed to elucidate the interaction effects of APs and T2DM on WM integrity and to examine how this interaction influences cognitive function. Methods This study included participants from the UK Biobank, categorized into a diabetes group and a control group (sample size: 665 vs. 13382). APs data, WM structure data, and cognitive data were incorporated into the analysis. Linear regression models were used to assess the interaction effect of T2DM and APs on WM structures and cognitive function, and then the mediation and moderation analyses were performed. Finally, propensity score matching (PSM) was performed at a 1:2 ratio to reselect the control group. After strictly controlling for covariates, the study results were validated. Results Significant interaction effects between T2DM and particulate matter ≤ 2.5µm (PM _2.5 ) were detected on the fractional anisotropy (FA) and oriented diffusivity (OD) values of the left inferior cerebellar peduncle (ICP). The FA value of the left ICP mediated the relationships between T2DM and both reaction time and digit symbol substitution test (DSST) scores. As the concentration of PM _2.5 increased, the mediating effect of FA became more pronounced. Additionally, both T2DM and APs had independent effects on multiple WM tracts, with APs primarily affecting the superior cerebellar peduncle (SCP). Conclusions Patients with T2DM have increased sensitivity of the left ICP to PM _2.5 , and this fiber tract plays a mediating role in the relationship between T2DM and cognitive function, with the mediating effect being moderated by PM _2.5 , highlighting the critical role of environmental pollution in brain function and behavioral health.