Association between accelerometer‐measured physical activity, genetic risk, and incident type 2 diabetes: A prospective cohort study

Abstract Aims To evaluate the dose–response relationship between the time spent on different types of physical activity and incident type 2 diabetes (T2D), and whether genetic risk would modify this relationship. Materials and Methods Based on data from 93,096 participants without T2D at baseline from the UK Biobank, we calculated hazard ratios (HRs) between accelerometer‐measured physical activity, including sedentary behaviour (SB), sleep, including light‐intensity physical activity (LIPA), and moderate‐to‐vigorous physical activity (MVPA), and the risk of developing T2D by using an isotemporal substitution model. The genetic risk of T2D was measured using standard polygenic risk scores (PRS) calculated by the UK Biobank database. Results Replacing 1 h/day of SB with other behaviours was associated with a 3% to 38% lower risk of T2D. Replacing 1 h/day of MVPA from other behaviours was associated with a 34% to 38% lower risk of T2D. These inverse associations remained consistent after stratification analyses according to T2D PRS. Among participants within the same genetic risk stratum, diminished MVPA engagement was associated with progressively weaker protection against T2D development. Interestingly, participants with intermediate genetic risk and high levels of MVPA showed a similar risk of T2D compared to those with low genetic risk and low levels of MVPA. Participants with high genetic risk and high levels of MVPA also showed comparable risk to those with intermediate genetic risk and low levels of MVPA. Conclusions Replacing other physical activities (SB, sleep, and LIPA) with MVPA was associated with a lower risk of T2D, and a high level of MVPA could partially mitigate the genetic risk, suggesting the considerable health benefits driven by a physically active lifestyle.