Training in the Fasted State, Glucose Metabolism and Energy Balance

Study Overview
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Brief Summary
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In healthy individuals, the body responds to glucose (sugar) ingestion by reducing the amount released from the liver. At the same time, skeletal muscles increase the rate at which they remove the glucose from the bloodstream, via the actions of the hormone insulin. This ensures that blood glucose levels remain in a controlled range. However, in developed countries, diseases such as metabolic syndrome and type 2 diabetes are becoming prevalent, due to dietary modifications and a reduction in physical activity. As one of the prominent barriers to regular physical activity is a lack of time, finding ways to maximize the health benefits of exercise is a priority for researchers. The investigators want to understand potential differences in the effects of six weeks of aerobic training, with the exercise performed either after breakfast or after a prolonged fast. Specifically, this research aims to investigate whether there is a difference in the change in processes implicated in glucose regulation and secondly, in subsequent eating and physical activity behaviors. By investigating these changes this work will explore how exercise and nutrition can be optimized to benefit health and weight loss.

Official Title
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Training in the Fasted State, Glucose Metabolism and Energy Balance

Conditions
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Glucose Metabolism Disorders

Intervention / Treatment
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* Behavioral: Exercise
* Behavioral: Breakfast
* Behavioral: Maintain habitual habits


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Aged 18-49 Body mass index (BMI) > 25 kg/m2 Weight stable for > 6 months Not currently engaging in any form of structured exercise Be able and willing to give informed oral and written consent Complete and meet the defined criteria of pre-study questionnaires and screen Exclusion Criteria: Have a history of metabolic, cardio-pulmonary or musculoskeletal disease Have plans to change diet and/or physical activity outside of the intervention Taking regular medication or food supplements from which it is not possible to refrain and which are known to influence any of the outcome measures. Failure to refrain from alcohol and/or caffeine containing drinks or strenuous exercise one day before or during the trial days Smokers Any reported condition or behavior deemed to pose a risk to the participant or introduce bias into the experiment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Control Group<br>Maintain habitual habits | Behavioral: Maintain habitual habits<br>* Normal physical activity and dietary behaviors maintained<br>|
| Active Comparator: Fed Exercise<br>6 weeks of moderate intensity exercise with breakfast consumption | Behavioral: Exercise<br>* Moderate intensity exercise<br>Behavioral: Breakfast<br>* Breakfast consumption<br>|
| Experimental: Fasted Exercise<br>6 weeks of moderate intensity exercise with breakfast omission | Behavioral: Exercise<br>* Moderate intensity exercise<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial plasma glucose concentrations | Response to oral glucose tolerance test (area under the curve) | 120 mins - (change after 6 weeks) | 
| Postprandial insulin concentrations | Response to oral glucose tolerance test (area under the curve) | 120 mins - (change after 6 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral Glucose Insulin Sensitivity Index | Response to oral glucose tolerance test | 120 mins - (change after 6 weeks) | 
| Cardiorespiratory fitness (VO2max) |  | Change after 6 weeks | 
| Habitual energy intake | Assessed via a food diary, completed at baseline and during the last week of the intervention | Change after 6 weeks | 
| Habitual energy expenditure | Assessed via an Actiheart monitor, completed at baseline and during the last week of the intervention | Change after 6 weeks | 
| Body mass (kg) |  | Change after 6 weeks | 
| Waist and hip circumference (cm) |  | Change after 6 weeks | 
| Maximal rate of whole-body lipid oxidation (g/min) | During an incremental exercise test | Change after 6 weeks | 
| Fasting plasma glucose concentration | Fasting plasma glucose concentration (mmol/L) | Basal Concentrations - (change after 6 weeks) | 
| Fasting plasma insulin concentration | Fasting plasma insulin concentration (pmol/L) | Basal Concentrations - (change after 6 weeks) | 
| Postprandial non-esterified fatty acid concentrations | Response to oral glucose tolerance test (total and incremental area under the curve) | 120 mins - (change after 6 weeks) | 
| Fasting plasma triglyceride concentrations | Fasting plasma triglyceride concentrations (mmol/L) | Basal Concentrations - (change after 6 weeks) | 
| Fasting plasma total cholesterol concentrations | Fasting plasma total cholesterol concentrations (mmol/L) | Basal Concentrations - (change after 6 weeks) | 
| Fasting plasma HDL cholesterol concentrations | Fasting plasma HDL cholesterol concentrations (mmol/L) | Basal Concentrations - (change after 6 weeks) | 
| Fasting plasma LDL cholesterol concentrations | Fasting plasma LDL cholesterol concentrations (mmol/L) | Basal Concentrations - (change after 6 weeks) | 
| Fasting plasma non-esterified fatty acid concentrations | Fasting plasma non-esterified fatty acid concentrations (mmol/L) | Basal Concentrations - (change after 6 weeks) | 
| Waist to hip ratio | Waist circumference (cm) divided by hip circumference (cm) | Change after 6 weeks | 
| Citrate Synthase Activity (mitochondrial citrate synthase activity in each muscle sample in an immunocapture based manner) | Skeletal muscle (vastus lateralis). Citrate Synthase Activity Assay Kit. | Change after 6 weeks | 
| Protein content of mitochondrial respiratory chain proteins | Skeletal muscle (vastus lateralis). Complex I, Complex II, Complex III, Complex IV. | Change after 6 weeks. For each participant the protein content will be presented as the fold change from baseline (arbitrary units). | 
| Protein content of carnitine palmitoyltransferase I (CPT-1) | Skeletal muscle (vastus lateralis) | Change after 6 weeks. For each participant the protein content will be presented as the fold change from baseline (arbitrary units) | 
| Protein content of cluster of differentiation 36 (CD36) | Skeletal muscle (vastus lateralis) | Change after 6 weeks. For each participant the protein content will be presented as the fold change from baseline (arbitrary units) | 
| Protein content (total and phosphorylated form) of AMP-activated protein kinase (AMPK) | Skeletal muscle (vastus lateralis) | Change after 6 weeks. For each participant the protein content will be presented as the fold change from baseline (arbitrary units) | 
| Resting metabolic rate (RMR) | Assessed via indirect calirometry | Change after 6 weeks | 
| Energy balance | Total energy expenditure minus total energy intake | Change after 6 weeks (during week 6 of intervention versus baseline monitoring) | 
| Whole-body lipid utilisation during exercise | Assessed via indirect calirometry during every exercise session (at ten minute intervals) | Change throughout complete training period (weeks 1 through to 6). Samples will be collected during every training session (three times weekly for six weeks) | 
| Whole-body carbohydrate utilisation during exercise | Assessed via indirect calirometry during every exercise session (at ten minute intervals) | Change throughout complete training period (weeks 1 through to 6). Samples will be collected during every training session (three times weekly for six weeks) | 
| Homeostasis Model Assessment (HOMA2-IR) | The Homeostasis Model Assessment (HOMA) estimate of steady state beta cell function (%B) and insulin sensitivity (%S). Derived from fasting plasma glucose and fasting plasma insulin concentrations. | Change after 6 weeks | 
| Fasting plasma glycerol concentrations | Fasting plasma glycerol concentrations (mmol/L) | Basal Concentrations - (change after 6 weeks) | 
| Postprandial plasma glycerol concentrations | Response to oral glucose tolerance test (total and incremental area under the curve) | Change after 6 weeks | 
| Adipose Tissue Insulin Resistance Index (Adipo-IR) | Response to oral glucose tolerance test (total and incremental area under the curve) | Change after 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Fasted, Glucose, Energy Balance