Frequent Activity Snacks Breaks

Study Overview
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Brief Summary
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There is a growing health burden in Sweden and Europe arising from the interrelated sequelae of metabolic disorders comprising impaired glucose tolerance (IGT), obesity and T2DM. Obesity and inactivity are the main drivers of IGT and T2DM and are responsible for up to 8% of health costs and 13% of deaths in Europe, with the risk of co-morbidities rising in parallel with increasing body weight. IGT and T2DM are the paradigm of inactivity-related disorders: the majority of people who have IGT or T2DM are overweight and inactive, with up to 80% being obese. A recent meta-analysis of 42 studies concluded that sedentary time was independently associated with a greater risk of T2D, all-cause mortality, cardiovascular disease incidence and mortality, and cancer incidence and mortality (breast, colon, colorectal, endometrial and epithelial ovarian cancers) (Ann Intern Med. 2015;162:123-32). A recent systematic review of trials published up to April 2014 identified 16 separate studies and concluded that there is considerable evidence of the positive effects of breaking up prolonged sitting time with light-intensity ambulatory physical activity and standing on postprandial metabolic parameters, including glucose, insulin and triglyceride levels (Med Sci Sports Exerc. 2015:47:2053-61). However, to date, all of the published experimental trials describing the beneficial effects of breaking up sitting time on metabolic risk markers have been restricted to acute exposure periods (1-5 days). We will perform a RCT intervention study, which examines the efficacy (clinically relevant responses) and practical implementation of low-impact training in sedentary obese individuals during the day.

Official Title
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Frequent Activity Snacks Breaks - Interrupting Sedentary Behaviour

Conditions
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Obesity, Insulin Resistance, Sedentary Lifestyle

Intervention / Treatment
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* Behavioral: Normal lifestyle
* Behavioral: Exercise
* Procedure: muscle and fat biopsy
* Device: Continuous glucose monitoring
* Device: Activity monitoring (ActivePal)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sedentary lifestyle, BMI 30-40 kg/m2 Exclusion Criteria: Unable to read Swedish (for informed consent), anticoagulant therapy, unability to perform intervention

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: No intervention<br>Normal lifestyle. Subjects will undergo a muscle and fat biopsy at the start of the 4 w period and after. An oral glucose test at the start and after completion of the 4 week period. Physical activity and glucose will be monitored during the study period. | Behavioral: Normal lifestyle<br>* Normal lifestyle<br>Procedure: muscle and fat biopsy<br>* Biopsy under local anesthesia<br>Device: Continuous glucose monitoring<br>* Glucose concentrations during the study period<br>Device: Activity monitoring (ActivePal)<br>* Objective measurements of standing and sitting time<br>|
| Experimental: Exercise intervention<br>Followed by a 1 week normal run in period subjects will undergo a 3 min bout, every half hour between 8 am and 6 pm comprises of simple low-intensity exercise such as moderate walking about or climbing a flight of stairs over a 3-week period. Subjects will undergo a muscle and fat biopsy at the start of the 4 w period and after. An oral glucose test at the start and after completion of the 4 week period. Physical activity and glucose will be monitored during the study period. | Behavioral: Exercise<br>* Mild exercise 3 min every half hour<br>Procedure: muscle and fat biopsy<br>* Biopsy under local anesthesia<br>Device: Continuous glucose monitoring<br>* Glucose concentrations during the study period<br>Device: Activity monitoring (ActivePal)<br>* Objective measurements of standing and sitting time<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in metabolic health including insulin resistance | Oral glucose tolerance test including baseline glucose and insulin | Change from baseline and 4 week intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes at the molecular level in skeletal and fat muscle biopsies | insulin signalling cascade, the pathways that regulate protein synthesis and atrophy, as well as the content and function of mitochondria | Change from baseline and 4 week intervention | 
| Changes at the molecular level in skeletal and fat muscle biopsies | The pathways that regulate protein synthesis and atrophy | Change from baseline and 4 week intervention | 
| Changes at the molecular level in skeletal and fat muscle biopsies | Lipid, protein and metabolites | Change from baseline and 4 week intervention | 
| Changes in gene expression | RNA, mRNA, DNA methylation | Change from baseline and 4 week intervention | 
| Changes in physical activity | Objective measures of standing and sitting | Change from baseline and 4 week intervention | 
| Changes in plasma glucose | Continuous glucose monitoring | Change from baseline and 4 week intervention |