Ambient air pollution, lifestyle, and genetic predisposition associated with type 2 diabetes: findings from a national prospective cohort study

The combined effects of ambient air pollution, lifestyle, and genetic predisposition on incident Type 2 Diabetes (T2D) have not been well documented.A total of 263,733 participants without T2D at baseline were identified from the UK Biobank. Annual concentrations of five air pollutants were estimated using Land Use Regression, while a healthy lifestyle score (HLS) was constructed using 7 major lifestyle factors, and polygenic risk score (PRS) was generated using 73 genetic variants. Cox regression was used to determine the association between air pollution and incident T2D for different HLS/PRS categories. Potential HLS/PRS interactions and population attributable fraction (PAF) were also examined.During a median follow-up of 11.94 years, 7827 (2.97 %) incident T2D cases were identified. Association between air pollution and incident T2D was stronger among those with higher HLS/PRS in a dose-response fashion. In addition, synergistic interactions between lifestyles and air pollution were observed. Lifestyle was the leading risk factor of T2D with a weighted PAF of 25.54 % (95 % CI: 19.22 %, 27.77 %) for intermediate HLS and 24.24 % (18.24 %, 26.36 %) due to unhealthy HLS. Overall, we estimated that about 25 % of T2D cases could be attributable to air pollution and associated interactions.Associations between air pollution and T2D were stronger among individuals with unhealthier lifestyle on an additive interaction scale. Public health interventions that address both reduction of exposure to high levels of air pollution in addition to lifestyle changes may have more benefit on reducing T2D risk than focusing on lifestyle changes alone.