ABSTRACTIntroductionThis cross-sectional study examined associations of device-measured sedentary time and moderate-to-vigorous physical activity (MVPA) with adipose tissue insulin resistance in people with or at high risk of type 2 diabetes (T2DM).MethodData were combined from six previous experimental studies (within our group) involving patients with T2DM or primary risk factors (median (interquartile range) age, 66.2 (66.0–70.8) yr; body mass index (BMI), 31.1 (28.0–34.4) kg·m⁻²; 62% male;n= 179). Adipose tissue insulin resistance was calculated as the product of fasted circulating insulin and nonesterified fatty acids (ADIPO-IR), whereas sedentary time and MVPA were determined from wrist-worn accelerometery. Generalized linear models examined associations of sedentary time and MVPA with ADIPO-IR with interaction terms added to explore the moderating influence of ethnicity (White European vs South Asian), BMI, age, and sex.ResultsIn finally adjusted models, sedentary time was positively associated with ADIPO-IR, with every 30 min of sedentary time associated with a 1.80-unit (95% confidence interval, 0.51–3.06;P= 0.006) higher ADIPO-IR. This relationship strengthened as BMI increased (β= 3.48 (95% confidence interval, 1.50–5.46),P= 0.005 in the upper BMI tertile (≥33.2 kg·m⁻²)). MVPA was unrelated to ADIPO-IR. These results were consistent in sensitivity analyses that excluded participants taking statins and/or metformin (n= 126) and when separated into the participants with T2DM (n= 32) and those at high risk (n= 147).ConclusionsSedentary time is positively related to adipose tissue insulin sensitivity in people with or at high risk of T2DM. This relationship strengthens as BMI increases and may help explain established relationships between greater sedentary time, ectopic lipid, and hyperglycemia.