Replacement of Sedentary Behavior by Various Daily-Life Physical Activities and Structured Exercises: Genetic Risk and Incident Type 2 Diabetes

OBJECTIVE To prospectively analyze the association of sedentary behavior time with type 2 diabetes (T2D) risk and perform the isotemporal substitution analyses to estimate the effect of substitution of sedentary behaviors by equal time of different types of daily-life physical activities and structured exercise. We also examined modifications by the genetic predisposition to T2D. RESEARCH DESIGN AND METHODS We included 475,502 participants free of T2D in the UK Biobank. Sedentary time was quantified by summing up the time spent on television watching, computer use, and driving. RESULTS During a median follow-up of 11 years, we documented 18,169 incident T2D cases. In comparison of the extreme categories (≥6 vs. <2 h/day), the hazard ratio for T2D was 1.58 (95% CI 1.47, 1.71) after adjustment for age, race, sex, lifestyle factors, and other covariates. Replacing 30 min of sedentary behavior per day with an equal amount of time of different types of daily-life activities and structured exercise was significantly associated with a 6-31% risk reduction of T2D, with strenuous sports showing the strongest (31%, 95% CI 24, 37) benefit. Moreover, we found a significant interaction between sedentary behavior and genetic predisposition for the risk of T2D (Pinteraction = 0.0008). The association was more profound among participants with a lower genetic risk of T2D. CONCLUSIONS Our study indicates that sedentary behavior time is associated with an increased risk of T2D; replacing sedentary behavior with a short duration (30 min/day) of daily-life physical activities or structured exercise is related to a significant reduction in T2D risk. Furthermore, such association was stronger among those with a lower genetic risk of T2D.