Engin, BuketWillis, Scott AMalaikah, SundusSargeant, Jack ABiddle, Gregory JHRazieh, CameronArgyridou, StavroulaEdwardson, Charlotte LJelleyman, CharlotteStensel, David JHenson, JosephRowlands, Alex VDavies, Melanie JYates, ThomasKing, James A2026-02-262026-02-262023-04-24Medicine and Science in Sports and Exercise, ISSN: 0195-9131 (Print); 1530-0315 (Online), Lippincott, Williams & Wilkins, 55(9), 1548-1554. doi: 10.1249/MSS.00000000000031930195-91311530-0315http://hdl.handle.net/10292/20688INTRODUCTION: 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.This is the Author's Accepted Manuscript of an article published in Medicine and Science in Sports and Exercise © 2023 by the American College of Sports Medicine. The Version of Record is available, free access, at DOI: 10.1249/MSS.000000000000319332 Biomedical and Clinical Sciences4206 Public Health42 Health Sciences3202 Clinical SciencesClinical ResearchObesityNutritionDiabetesPreventionMetabolic and endocrine1106 Human Movement and Sports Sciences1116 Medical Physiology1117 Public Health and Health ServicesSport Sciences3202 Clinical sciences3208 Medical physiology4207 Sports science and exerciseHumansMaleAdultAgedFemaleInsulin ResistanceDiabetes Mellitus, Type 2Sedentary BehaviorCross-Sectional StudiesAdipose TissueAdipose TissueHumansDiabetes Mellitus, Type 2Insulin ResistanceCross-Sectional StudiesAdultAgedFemaleMaleSedentary BehaviorHumansMaleAdultAgedFemaleInsulin ResistanceDiabetes Mellitus, Type 2Sedentary BehaviorCross-Sectional StudiesAdipose TissueJournal ArticleOpenAccess10.1249/MSS.0000000000003193