<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>