title: Sedentary time and markers of chronic low-grade inflammation in a high risk population.
abstract: BACKGROUND
  Sedentary behaviour has been identified as a distinct risk factor for several health outcomes. Nevertheless, little research has been conducted into the underlying mechanisms driving these observations. This study aimed to investigate the association of objectively measured sedentary time and breaks in sedentary time with markers of chronic low-grade inflammation and adiposity in a population at a high risk of type 2 diabetes mellitus.
  
  
  METHODS
  This study reports data from an ongoing diabetes prevention programme conducted in Leicestershire, UK. High risk individuals were recruited from 10 primary care practices. Sedentary time (<25 counts per 15 s) was measured using Actigraph GT3X accelerometers (15 s epochs). A break was considered as any interruption in sedentary time (≥25 counts per 15 s). Biochemical outcomes included interleukin-6 (IL-6), C-reactive protein (CRP), leptin, adiponectin and leptin:adiponectin ratio (LAR). A sensitivity analysis investigated whether results were affected by removing participants with a CRP level >10 mg/L, as this can be indicative of acute inflammation.
  
  
  RESULTS
  558 participants (age = 63.6±7.7 years; male = 64.7%) had complete adipokine and accelerometer data. Following adjustment for various confounders, sedentary time was detrimentally associated with CRP (β = 0.176±0.057, p = 0.002), IL-6 (β = 0.242±0.056, p = <0.001), leptin (β = 0.146±0.043, p = <0.001) and LAR (β = 0.208±0.052, p = <0.001). Associations were attenuated after further adjustment for moderate-to-vigorous physical activity (MVPA) with only IL-6 (β = 0.231±0.073, p = 0.002) remaining significant; this result was unaffected after further adjustment for body mass index and glycosylated haemoglobin (HbA1c). Similarly, breaks in sedentary time were significantly inversely associated with IL-6 (β = -0.094±0.047, p = 0.045) and leptin (β = -0.075±0.037, p = 0.039); however, these associations were attenuated after adjustment for accelerometer derived variables. Excluding individuals with a CRP level >10 mg/L consistently attenuated the significant associations across all markers of inflammation.
  
  
  CONCLUSIONS
  These novel findings from a high risk population recruited through primary care suggest that sedentary behaviour may influence markers associated with inflammation, independent of MVPA, glycaemia and adiposity.
authors.affiliation: National Institute for Health Research (NIHR) Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester, Leicestershire, United Kingdom ; Diabetes Research Centre, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, Leicestershire, United Kingdom.
authors.forename: Joseph
authors.initials: J
authors.lastname: Henson
authors.forename: Thomas
authors.initials: T
authors.lastname: Yates
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Edwardson
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Khunti
authors.forename: Duncan
authors.initials: D
authors.lastname: Talbot
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Gray
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Leigh
authors.forename: Patrice
authors.initials: P
authors.lastname: Carter
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D050154:Adiposity / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D012307:Risk Factors; D057185:Sedentary Behavior
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D015850:Interleukin-6; D020738:Leptin