• Higher summer UHI exposure was significantly associated with increased T2D incidence. • Significant interactions were observed between UHI intensity and genetic risk. • Proteomic signatures partially mediated the UHI intensity-T2D association. The urban heat island (UHI) effect is increasingly recognized as an environmental risk factor for human health, yet its association with type 2 diabetes (T2D) and underlying mechanisms remain poorly understood. This study investigated the impact of summer UHI exposure on T2D incidence, while examining the modifying role of genetic susceptibility and the mediating effects of plasma proteins. This study analyzed 398,825 UK Biobank participants free of T2D at baseline, including a subset of 43,023 with proteomic data. Cox proportional hazards models were used to evaluate the association between summer UHI intensity and T2D risk. A polygenic risk score for T2D assessed potential gene-environment interactions. Mediation analyses further explored the roles of proteomic signatures and individual proteins in linking UHI exposure to T2D. High summer UHI exposure was associated with elevated T2D risk compared with low exposure. Subgroup analyses revealed heightened susceptibility among males and those with preexisting cardiovascular disease or cancer. Significant interactions were observed between UHI intensity and genetic risk. Participants with high genetic risk and high UHI exposure exhibited the greatest T2D incidence relative to those with low genetic risk and low exposure. Proteomic profiling identified 339 UHI-associated proteins, and mediation analyses demonstrated that proteomic signatures (mediation proportion: 13.0%) partially mediated the UHI-T2D association. Summer UHI exposure is linked to increased T2D risk, with genetic factors modifying this relationship and plasma proteins serving as potential mediators. These findings offer novel mechanistic insights and underscore the need for urban planning strategies to mitigate heat-related diabetes burdens.
Ren et al. (Wed,) studied this question.