Arming Health: Can Breaking up Restful Sitting Time With Upper Body Contractile Activity Regulate Metabolic Health.
Condition: Diabetes
Study type: Interventional

Summary: 
      Research shows that sitting for long periods of time on a regular basis is bad for health and
      can leave individuals more susceptible to Obesity, Cardiovascular Disease, Type 2 Diabetes
      and premature death regardless of exercise engagement outside of these seated hours.

      As sitting is so common in modern society it is vital that research explores ways to protect
      individuals from this worsening issue. Investigators want to see if breaking up long periods
      of sitting time with short, frequent bouts of light physical activity, while remaining
      seated, is enough to alleviate these risk factors.
    

Detailed description: 
      - Familiarisation screening visit - (Visit 1) Before participating in the study, all
      participants will visit the exercise laboratory for a familiarisation and screening visit
      where they will be shown the designated experimental area, provide written informed consent
      and have various measurements taken.

      All participants will be required to fast from 10pm onwards the evening prior to this first
      visit (drinking water is allowed). Participants will then be provided with a standardised
      breakfast on arrival (after consent has been obtained). This meal will be prescribed
      according to body mass and will provide approximately 8 kcals per kg of bodyweight made up of
      13-14% protein, 51-52% carbohydrate and 35% fat. Typical ingredients used here will be; Plain
      bagels with margarine and a protein powder mixed with whole milk.

      Alternative ingredients matching the nutritional content of this meal will be explored in
      light of special dietary preferences (i.e. vegan) or food allergies (i.e. lactose
      intolerance).

      It is also important that participants avoid general exercise and drinking alcohol or coffee
      in the 48 hours (2 days) leading up to this first visit (and the remaining two visits), this
      will be made clear in the participant information sheet. Very strenuous exercise must be
      avoided 72 hours (3 days) prior.

      Participants will be asked to record all food and drink consumed the day before this first
      visit. They will then be asked to replicate this diet the day before the remaining visits
      using their dietary record to guide them. Therefore, all meals leading up to each visit will
      be standardised and will not confound the results.

      The measurements taken during this visit include; basic anthropometry (body mass, waist
      circumference, body fat %); blood pressure; biochemical variables (HbA1c and blood lipids and
      CRP); Energy expenditure (at rest, during slow steady state treadmill walking and at numerous
      intensities on an arm ergometer machine); and measures of objectively determined free-living
      physical activity, sedentary behaviour and posture.

      Anthropometry measurement at visit 1 Arterial blood pressure will be measured in the sitting
      position. Three measurements will be obtained and the average of the last two measurements
      will be used.

      Basic anthropometric measures such as body mass and body fat percentage (measured through bio
      impedance analysis) will be taken alongside height and waist circumference (midpoint between
      the lower costal margin and iliac crest). These will be recorded to the nearest 0.1kg, 0.5%,
      0.5cm and 0.5cm respectively.

      Biochemical variables collected at visit 1 During visit one a blood sample will be taken
      whereby HbA1c (Glycated Haemoglobin), CRP (C-Reactive Protein) and lipid profile will be
      measured. All venepuncture will be undertaken by trained health care professionals and all
      biochemical analyses will be conducted blinded to treatment condition. All participants will
      be sent an individual results letter highlighting their main clinical results after the
      familiarisation visit. With the participants consent, all results will be copied to their GP.
      Any participant whose Hba1c is 6.5% or above will be sent an individual results letter
      strongly advising them to make an appointment with their GP as soon as possible to discuss
      their results in more detail, as this is indicative of Diabetes. Similarly, any participant
      whose HbA1c is between 6 and 6.4% will also be sent an individual results letter advising
      them to make an appointment with their GP if they are concerned, as this is indicative of
      pre-diabetes. With the participants consent, the GP will also be notified of the situation
      and sent a results letter

      Energy Expenditure testing during visit 1 During visit one, the energy expenditure at rest,
      while walking at 3km/hr and while performing arm ergometry at different intensities will be
      measured via respiratory gas collected from the participants using the Cortex or GEM
      breath-by-breath automated gas-analysis system.

      In order to assess resting energy expenditure, each participant will be asked to sit quietly
      (refraining from movement) for 30 minutes while wearing a gas mask/hood. Expired gas data
      will then be collected over the latter half of this 30 minute period once values have
      stabilised.

      Following this, walking will be performed at 3km.hr on a treadmill for 10 minutes (also while
      wearing a gas mask), from which expired gas data will be collected in the latter 5 minutes.

      Light arm ergometry while seated will then be performed at 5 minute intervals (across
      numerous intensities) from which expired gas data will be collected in the 2nd 3rd and 4th
      minutes, discarding both the first and last minute. Participants will also remove the
      face-mask for 5minutes in between each 5 minute bout in order to allow participants to
      recover and for energy expenditure outputs to return to their resting level prior to the next
      activity bout.

      This data will consequently dictate the intensity of arm ergometry to be performed when
      breaking up sitting time, as investigators would like the energy expenditure of these seated
      breaks to closely resemble that of light walking. This allows investigators to further
      elucidate the role of posture alone as energy expenditures will be kept relatively consistent
      with that of previous research, allowing direct comparisons to be made.

      Objective measures of physical activity at visit 1 Participants will be issued with an
      Actigraph accelerometer to measure the time spent sedentary and in moderate to vigorous
      physical activity under free-living conditions. Participants will be asked to wear this
      accelerometer (placed on right anterior axillary line) for 7 days after the familiarisation
      visit, up to 7 days leading up to the treatment conditions and throughout the experimental
      conditions in order to monitor any potential changes in physical activity levels and make
      sure participants have avoided exercise in the days leading up to the treatment conditions.
      Outputs will include steps per day, total body movement (counts per day), and time in
      sedentary, light, moderate and vigorous-intensity physical activity as determined by counts
      per minute cut points proposed by Freedson et al. (21)

      Posture and sedentary time data collection at visit 1 Postural allocation (sitting and
      standing) and walking will be quantified using an activPAL physical activity monitor (PAL
      Technologies, Glasgow, Scotland). The activPAL is a single-unit monitor based on a triaxial
      accelerometer that is worn midline on the anterior aspect of the thigh and attached directly
      onto the skin using medical dressing. The monitor produces a signal related to thigh
      inclination and has been shown to be a valid and reliable measurement tool for determining
      posture during activities of daily living in a healthy population (22). Outputs from this
      device include; time spent sitting, standing, stepping and sit-to-stand transitions. The
      device will be worn for 7 days after the familiarisation visit, (alongside the Actigraph) and
      throughout experimental conditions.

      - Experimental treatment conditions (Visits 2 and 3) In the weeks following this initial
      familiarization visit, participants will be assigned to receive the following two treatment
      conditions (A: Prolonged sitting and B: Light arm ergometry breaks) in a random order using
      an online randomisation tool. Each treatment condition will be carried out on one single day.
      In total, the study requires three separate visits to the Leicester Diabetes Centre,
      Leicester General Hospital, University Hospitals of Leicester; familiarisation visit, first
      treatment condition and second treatment condition.

      Where participants have limited access to motorised transport, taxis will be provided to
      reduce ambulatory activity involved in the commute to and from each visit.

      For male participants, there will be a minimum of 7 days between each treatment condition.
      For females, there will be a gap of one month (or near as possible) due to the potential that
      different phases of a women's menstrual cycle may affect their blood glucose response to a
      meal (23). Testing at similar times of the month avoids this potential variability. However,
      if a female participant reports being post-menopausal on their pre-screening questionnaire
      then a minimum of 7 days between treatment conditions will be used.

      Treatment Condition A: Prolonged sitting During the prolonged sitting condition, participants
      will be restricted from walking and standing. They will be in a designated room equipped with
      a chair/desk and have access to a computer with internet services, books and magazines or
      movies throughout the day. Lavatory breaks will be permitted and a wheelchair will be used to
      wheel the participants to the toilet to reduce upright activity.

      The day before each treatment condition, participants will be asked to consume the same type
      and quantity of food and drink that they recorded prior to their familiarisation visit.
      Participants will also be asked to avoid alcohol, caffeine and moderate intensity exercise
      for 2 days prior to each treatment condition (as done prior to visit one) as reproducibility
      data has shown that insulin and triglyceride responses to meal ingestion are good under these
      conditions (24). Furthermore, there is evidence that the effect of a single exercise session
      on insulin sensitivity and glucose tolerance may last up to 48 hours (25). Strenuous exercise
      should be avoided for 3 days prior to each treatment condition, as this has been found to
      increase insulin sensitivity for up to 72 hours (26).

      Participants will be asked to fast the night before both treatment conditions (and prior to
      familiarisation as discussed previously) from 10pm onwards. On the morning of the test,
      participants will have a cannula inserted into an accessible vein by a trained health care
      professional and the first of the blood samples will be taken (this represents time point:
      -1hr according to figure 1). Blood pressure measurements will be taken immediately before
      each blood sample alongside self-reported measures of positive affect, mood and sleepiness
      (see description under secondary outcomes section 3.0). Once the cannula has been inserted
      and the first blood sample taken, participants will then be asked to sit quietly for 60
      minutes in order to achieve a steady state. During this time, participants will be expected
      to complete a battery of cognitive function tests lasting approximately 25 minutes (see
      description under secondary outcomes section 4.0).

      Following this 60 minute period, participants will have another blood pressure measurement,
      positive affect, mood and sleepiness assessment and blood sample taken, at which point they
      will then be provided with a standardised mixed meal breakfast (09:00am) (time point: 0h).
      The meal will be prescribed according to body mass and will provide approximately 8kcals per
      kg of bodyweight made up of 13-14% protein, 51-52% carbohydrate and 35% fat. A mixed-meal of
      this nature will be used to ensure ecological validity as fat and carbohydrates are usually
      co-ingested in real-life situations. Blood sampling alongside positive affect, mood,
      sleepiness and blood pressure measurements will continue at 30, 60, 120 and 180 minutes
      following breakfast. A second, lunch meal (12:00pm) (with identical nutrient composition to
      breakfast), will then be consumed over 15 minutes. Blood pressure, positive affect, mood,
      sleepiness and blood sampling will continue at 30, 60, 120 and 180 minutes following lunch
      (Figure 1). Participants will then repeat the battery of cognitive function tests after their
      final blood sample is taken. All participants will remain sitting throughout the test period
      whilst undertaking typical sedentary pursuits such as watching TV/DVDs/reading.

      Treatment Condition B: Light arm ergometry breaks This will be identical to the prolonged
      sitting condition (Treatment A), but participants will be required to break up their restful
      sitting time with seated upper body contractile activity. This will be implemented in the
      form of arm ergometry breaks for 5 minutes every 30 minutes following both breakfast and
      lunch. In total, individuals will accumulate 12 bouts (60 minutes) of light intensity arm
      ergometry.

      The main reason for utilising 5 minute bouts every 30 minutes was to achieve a balance
      between frequency and utility, as having to interrupt sitting time too regularly has less
      real world application, especially in an office based environment where prolonged sitting is
      most prevalent. Previous research has also found positive findings while interrupting sitting
      time in this manner (38).

      The intensity (speed and resistance) of these arm ergometry breaks will have been derived
      from the energy expenditure tests conducted in visit 1, as investigators are aiming to match
      the intensity of arm ergometry to that of light walking at 3km/hr.
    

Intervention name(s): Prolonged Sitting; Light arm ergometry breaks
Intervention type(s): Other; Other
Intervention description(s): Condition A is referred to as the 'sitting' condition. Here participants will remain seated throughout the whole of the 7 ½ hour test period (8am - 3:30pm). On arrival, participants will have a cannula (a small tube that allows us to take blood) inserted into their arm; this will stay in the arm and allow investigators to take regular blood samples throughout the day. Blood samples and blood pressure will be taken at 30, 60, 120 and 180 minutes after breakfast. Following this, a lunch meal will be provided and investigators will continue taking blood samples and blood pressure at 30, 60, 120 and 180 minutes after this lunch meal. In total, 10 blood samples will be taken over the 7 ½ hour testing period. There will also be a cognitive test in the morning and afternoon.; Condition B is the 'light activity breaks' condition. Participants will go through exactly the same process as condition A but will also be asked to do 5 minute bouts of light intensity arm ergometry on a desktop arm ergometer every 30 minutes following breakfast and lunch. In total they will do 12 five minute arm ergometry breaks throughout the 7 ½ hour test period (60 minutes of arm ergometry in total). In total 10 blood samples will be taken on the day.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Sedentary behaviour; Postprandial glycaemic response