Effects of Microbouts of Activity on Metabolic Health

Population studies suggest that time spent in sedentary behaviors is associated with all-cause mortality including obesity, diabetes, and cardiovascular diseases, independent of time spent in exercise. Frequent interruptions to sedentary time are however beneficially associated with metabolic health outcomes, even in individuals who exercise regularly. The goal is to use integrative approach to understand the biological mechanisms that underlie these associations in a longitudinal intervention study in overweight sedentary adults. The investigators believe that the proposed study will provide an initial evidence base for the health benefits of breaking up prolonged sitting with short bursts of activity. This innovative strategy may be more effective at combating the adverse effects of sedentary behaviors than more traditional approaches.

Study Overview

• Status: Completed
• Conditions: Health Behavior
• Intervention / Treatment: Behavioral: Traditional Exercise Training; Behavioral: Daily Microbursts of Activity

Detailed Description

To compare the effects of 6-weeks of microbursts of moderate-intensity activity to a calorically equivalent single bout of 45 minutes of moderate-intensity exercise training, both performed 5 days per week for a total of 45 minutes, in free-living sedentary overweight adults on:

Aim 1: plasma inflammatory and cardiometabolic health biomarkers in association with total energy expenditure and time spent in sedentary behaviors.

H1: Microbursts of activity will result in higher daily energy expenditure and lower time spent sedentary, as respectively measured with doubly labeled water and accelerometry, than traditional exercise training. This will be associated with healthier inflammatory Interleukin 1 alpha (IL1a), Interleukin 6 (IL6), Interleukin 10 (IL10), Tumour Necrosis Factor alpha (TNFa) and cardiometabolic (triglycerides, cholesterol, C-Reactive Protein (CRP), High-density lipoprotein (HDL), and Low-density lipoprotein (LDL) profiles compared to those obtained with traditional exercise training program.

Aim 2: 24-hr total fat and carbohydrate oxidation, exogenous carbohydrate oxidation, dietary fat trafficking between oxidation and incorporation into muscle lipid fractions, and mitochondrial function.

H2: Both one single continuous bout and microbouts of activity will increase 24-hr total (whole-room calorimetry) and dietary (D31-palmitate) fat oxidation due to greater mitochondrial lipid oxidation (high resolution respirometry) and lower incorporation of dietary fatty acid into muscle lipid fractions (D31-palmitate), as compared to baseline sedentary control condition. Microbouts of activity will further result in greater increases in 24-hr total (whole-room calorimetry) and exogenous (U-13C6 glucose) carbohydrate oxidation and in mitochondrial carbohydrate-linked oxidation, than traditional isocaloric exercise training.

Aim 3: Whole-body insulin sensitivity and daily glucose mean and variability. H3: Both one single continuous bout and microbouts of activity will improve whole-body insulin sensitivity Intravenous Glucose Tolerance Test (IVGTT) compared to the baseline sedentary condition, but the improvement will likely be higher with the microbouts of activity. However, only the microbouts of activity will improve postprandial glycemia and the daily oscillations in glucose level as measured by CGM.

Exploratory aim: Self-perceived appetite and hunger.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Overweight but weight stable (+/- 3kg over previous 6 months) sedentary male and female adults (n=30) will be recruited.
• Ages between 18-45 years old
• BMI of 25-35 kg/m2
• Sedentary ( self report < 150min/wk of moderate-to-vigorous activity or less than 6,500 steps per day as measured for 5 days in free-living conditions with a pedometer).
• The use of birth pill control will be accepted

Exclusion criteria:

• Any history of renal (present or past kidney failure, kidney transplant, dialysis or kidney cysts),
• Uncontrolled hypertension
• Cardiovascular (present or past atherosclerosis, heart attack, ischemic stroke, heart failure)
• Hepatic diseases (past or present hepatitis B or C, fibrosis, cirrhosis, NAFLD/NASH)
• Type 1 or 2 diabetes
• Cancer
• Smoking
• Consumption of drugs (marijuana included)
• Consumption of alcohol (>40g/d)
• HIV positivity
• Psychiatric disorders
• Any medications known to interfere with lipid or energy metabolism
• Known physical activity contraindications
• Major illness/physical problems (acute or chronic) that may limit their ability to perform the walking activities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Traditional Exercise Training; Participants will be asked to perform moderate-intensity exercise (brisk walking) for 45 minutes for 5 days/week for 6 weeks. This intervention corresponds to the current recommendations.	Behavioral: Traditional Exercise Training; Participants will be asked to perform moderate-intensity exercise (brisk walking) for 45 minutes for 5 days/week for 6 weeks. This intervention corresponds to the current recommendations.
Experimental: Daily Microbursts of Activity; Participants will be asked to break up their sedentary activities of daily living for 5-minutes every hour for 9 hours, 5 days/week, by brisk walking for 6 weeks.	Behavioral: Daily Microbursts of Activity; Participants will be asked to break up their sedentary activities of daily living for 5-minutes every hour for 9 hours, 5 days/week, by brisk walking for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in sedentary time as measured by ActiPAL	Over each 2 week period, participants will be instructed to wear an ActiPAL (PALTechnologies: Glasgow, Scotland) activity monitor on their right leg. Participants will be instructed to wear the monitors at all times except when sleeping or participating in water-based activities. The time-stamped "event" data file from the activPAL software will be used to determine time spent sitting/lying, standing and stepping per day.	weeks 1-2 and weeks 5-6
Changes in insulin sensitivity	Insulin sensitivity will be determined via an insulin modified frequently sampled intra-venous glucose tolerance test (IVGTT). After baseline samples, intravenous glucose (0.3 g/kg) will be infused over 1 minute, followed by insulin at 0.03 U/kg, 20 minutes after glucose administration. Blood samples will be frequently sampled over 5 hours, and insulin sensitivity will be calculated using the Bergman minimal model.	Week 2 and week 8
Postprandial glycemia	Incremental area under the curve of plasma glucose concentration measured in fasting and every hour for 14 hours.	Week 2 and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in total energy expenditure (TEE)	Total energy expenditure (TEE) will be measured before and at the end of the intervention using doubly labeled water (DLW) over a 10-day period, as previously described (31). Subjects will ingest premixed 2g/kg total body water (TBW), estimated as 73% of fat free mass) dose of DLW composed of 0.2 and 0.15 g/kg estimated TBW of H218O and 2H2O, respectively. Urine samples will be collected in duplicate on days 0, 6, 8 and 10. 2H and 18O enrichment will be determined in urine samples by isotope ratio mass spectrometry (Delta V Advantage IRMS)	week 1-2 and week 5-6
Changes in Moderate-to-vigorous physical activity as measured by ActiGraph	Over the same 10-day period, participants will be instructed to wear an Actigraph GT3X+ accelerometer (Actigraph, LLC, Fort Walton Beach, FL) on their hip. Participants will be instructed to wear the monitors at all times except when sleeping or participating in water-based activities.	weeks 1-6
Changes in Mitochondria function	Freshly isolated skeletal muscle biopsies will be cut into small samples, the fibre bundles separated mechanically and partially teased apart and permeabilised. Small samples (2-5mg) will be added to the 2ml chamber of an Oroboros high-resolution respirometer with a mitochondrial respiration buffer. With the addition of several substrates, different states will be reached to analyse mitochondrial function. Pyruvate, malate and glutamate will be added as substrates to examine respiration through Complex I, succinate will be used to examine respiration through Complex II and octanoylcarnitine will be used to examine respiration through the electron-transferring flavoprotein, ETF.	week 2 and week 7
24hr substrate oxidation and energy expenditure	Gas exchange are measured for 24hr by whole room calorimetry and nitrogen excretion is measured in the urines collected for 24hr. 24hr energy expenditure is then calculated using 24hr VCO2, 24hr VO2 and 24hr urinary nitrogen excretion with the Weir equation. 24hr carbohydrate, fat and protein oxidation are calculated using 24hr VCO2, 24hr VO2 and 24hr urinary nitrogen excretion with the Frayn equation.	Week 2 and week 8
Changes in Dietary Carbohydrate Oxidation	After the investigators have shown the subjects the procedure, subjects will collect their own hourly breath sampling for CO2 by blowing through a straw into two 15ml Vacutainers. Breath CO2 will be sampled directly from the Vacutainer with a syringe, and 13CO2 /12CO2 measured with IRMS.	week 2 and week 8
Changes in Dietary Fat Oxidation	Hourly urine sampling will be collected by the subjects for 24 hours and stored in 5mL cryovials at -20C until further analysis. To measure 2 hour fat oxidation, 2 hour/1 hour ratios from urine samples will be analyzed, as above described for the doubly labeled water method. The oxidation rate of glucose/water will be calculated from the cumulative recovery of 2 hours in total body water (TBW) as detailed previously.	week 2 and week 8
Postprandial insulinemia	Incremental area under the curve of plasma insulin concentration measured in fasting and every hour for 14 hours.	Week 2 and week 8
Postprandial NEFA	Incremental area under the curve of plasma NEFA as measured in fasting state and every hour for 14 hours.	Week 2 and week 8
Postprandial triglyceridemia	Incremental area under the curve of plasma TG as measured in fasting state and every hour for 14 hours.	Week 2 and week 8
Daily glucose mean and oscillation	Daily interstitial glucose mean and oscillations as measured by continuous glucose monitoring for 14 consecutive days.	Weeks 1-2 and weeks 5-6
Changes in plasma inflammatory markers	Fasting blood samples will be obtained for the measurements of Interleukin 1 alpha (IL1a), Interleukin 6 (IL6), Interleukin 10 (IL10), Tumour Necrosis Factor alpha (TNFa) and cardiometabolic (triglycerides, cholesterol, C-Reactive Protein (CRP).	Week 2 and week 8
changes in plasma total cholesterol, HDL and LDL	Fasting plasma blood draw for the measurement of total cholesterol, HDL and LDL.	Week 2 and week 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-perceived appetite and hunger	Self-perceived hunger, satiety and prospective food consumption as measured by visual analog scale before and after standard breakfast, lunch, and dinner.	Week 2 and week 8

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Audrey Bergouignan, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2017
• Primary Completion (Actual): October 8, 2021
• Study Completion (Actual): October 8, 2021

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimated): December 21, 2016

Study Record Updates

• Last Update Posted (Actual): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Sedentary Behavior
• Other Study ID Numbers: 16-1769

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No