Sedentary time is independently related to adipose tissue insulin resistance in adults with or at risk of type 2 diabetes

Introduction: This 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). Methods: Data were combined from six previous experimental studies (within our group) involving patients with T2DM or primary risk factors (median (IQR) age 66.2 (66.0 – 70.8) years, 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 non-esterified fatty acids (ADIPO-IR), while sedentary time and MVPA were determined from wrist-worn accelerometery. Generalised 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. Results: In finally-adjusted models, sedentary time was positively associated with ADIPO-IR, with every 30-min of sedentary time associated with a 1.80 (95% CI: 0.51 to 3.06; P = 0.006) unit higher ADIPO-IR. This relationship strengthened as BMI increased (β= 3.48 [95%CI=1.50 to 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). Conclusions: Sedentary 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 hyperglycaemia.