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

<b>Objective: </b>To prospectively analyze the association of sedentary behavior time with T2D risk and perform the iso-temporal substitution analyses to estimate the effect of substituting 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. <p><b>Research Design and Methods: </b>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 using, and driving.</p> <p><b>Results: </b>During a median follow-up of 11 years, we documented 18,169 incident T2D. Comparing the extreme categories (≥6 vs. <2 hours/day), the hazard ratio (HR) for T2D was 1.58 (95% CI, 1.47-1.71), after adjustment for age, race, sex, lifestyle factors, and other covariates. Replacing 30 minutes of sedentary behavior per day with an equal time of different types of daily-life activities and structured exercise were 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 on the risk of T2D (p-interaction=0.0008). The association was more profound among participants with a lower genetic risk of T2D.</p> <p><b>Conclusions: </b>Our study indicates that sedentary behavior time is associated with an increased risk of T2D; replacing sedentary behavior with a short-duration (30 minutes/day) 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.</p>