Influence of Prior Walking on Postprandial Metabolism in Centrally Obese Men

Study Overview
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Brief Summary
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The present study will investigate the effect of prior walking on postprandial metabolism and endothelial function in centrally obese South Asian and White European men. Participants will complete two, 2-day trials in a random, crossover design separated by at least a week. On day 1, participants will either rest or complete a 60 minute walk at 60% maximal oxygen uptake. On day 2, participants will arrive at 08:00 having fasted overnight and a baseline venous blood sample and endothelial function measurement will be taken. Participants will consume a high-fat breakfast and lunch and 12 subsequent venous blood samples will be taken throughout the day at standardised intervals to measure a variety of coronary heart disease risk markers. A second endothelial function measurement will be completed 2 hours after the breakfast. Blood pressure will be measured every hour. It is expected that the South Asian participants will have impaired metabolism and endothelial function compared to their European counterparts but the bout of exercise performed on day 1 will mitigate these responses.

Detailed Description
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South Asians have a higher-than-average risk of coronary heart disease. The reasons for this are unclear, but physical inactivity and/or poor responsiveness to exercise may play a role. It is important to understand the effect of exercise on endothelial function and coronary heart disease risk markers in the hope that exercise can be prescribed as an effective treatment to mitigate endothelial dysfunction and the risk of heart disease. Previous research from the investigators' laboratory has indicated that postprandial metabolism is impaired in South Asian men, but this, and other coronary heart disease risk markers, can be improved with acute exercise. However, the previous research was conducted in apparently healthy South Asian and White European men. The investigators now wish to quantify and compare the coronary heart disease risk marker and endothelial function response to acute exercise in centrally obese South Asian and White European individuals who are at a higher risk for diabetes and cardiovascular disease. On visit 1, participants will attend the laboratory to undergo preliminary assessments and to be familiarised with the laboratory environment and study procedures. Specifically, health status, habitual physical activity, dietary habits and anthropometric data (height, weight, waist and hip circumference, body fat) will be collected. A HbA1c test will be performed to check participants are not diabetic. The modified Bruce Treadmill test will be performed to predict maximal oxygen uptake. On visit 2, participants will undergo a magnetic resonance imaging (MRI) scan to quantify regional body composition comprising abdominal subcutaneous adipose tissue, visceral adipose tissue, liver fat percentage, thigh intramuscular adipose tissue and thigh muscle volume. On visits 3-6 participants will complete two, 2-day trials in a random, crossover design separated by at least 1 week. On day 1 of both trials, participants will arrive fasted at 08:00 and a baseline blood sample, blood pressure and endothelial function measurement will be taken. Participants will consume a standardised high fat breakfast at 09:00 and lunch at 13:00. At 15:30 the participants will walk for 60 minutes at 60% maximal oxygen uptake and complete a second endothelial function measurement at 16:45. Participants will leave the laboratory with a standardised evening meal to consume before 22:00. The control trial will be the same, except no exercise will be performed. On day 2, participants will arrive at 08:00 having fasted overnight for 10h (except plain water). A cannula will be inserted into the antecubital vein for collection of venous blood samples. Blood pressure will be measured at 08:00 (0h) and again at hourly intervals throughout the day. Endothelial function will measured at 08:15 (0.25h) and again at 3h. At 0h, a fasting blood sample will be collected. Subsequent venous blood samples will be collected at 1.5, 1.75, 2, 3, 4, 5, 5.5, 5.75, 6, 7, 8 and 9h. Participants will consume a standardised high fat breakfast at 1h and a standardised high fat lunch at 5h. The meals consist of 57% fat, 32% carbohydrate and 11% protein. The meals provide 14.3 kcal per kg of body mass. Participants will rest in the laboratory throughout day 2 of both the exercise and control trials.

Official Title
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Influence of Prior Walking on Endothelial Function and Coronary Heart Disease Risk Markers in Centrally Obese South Asian and White European Men

Conditions
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Diabetes Mellitus, Type 2, Cardiovascular Diseases, Endothelial Dysfunction, Insulin Resistance, Oxidative Stress

Intervention / Treatment
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* Behavioral: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 60 year old South Asian and White European men; Centrally obese (waist circumference >90cm for South Asians, >94cm for White Europeans); Weight stable for the past 3 months; Non-smokers; No known contradictions to maximal exertion exercise. Exclusion Criteria: Musculoskeletal injury that has affected normal ambulation within the last month; Congenital heart disease; Any muscle or bone injuries that do not allow them to walk on a treadmill; Uncontrolled exercise-induced asthma; Coagulation or bleeding disorders; Diabetes (metabolism will be different to non-diabetics potentially skewing the data); Taking any medication that might influence fat metabolism; Taking any medication that might influence blood glucose (e.g., insulin for diabetes); Heart conditions; Smoking; Dieting or restrained eating behaviours; Weight fluctuation greater than 3 kg in the previous 3 months to study enrolment; A food allergy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Exercise<br>Exercise: Participants will walk for 60 minutes at 60% maximal oxygen uptake on day 1. | Behavioral: Exercise<br>* A 60 minute walk at 60% maximal oxygen uptake.<br>|
| No Intervention: No Intervention: Control<br>Participants will rest on day 1. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Triacylglycerol changes in response to exercise and feeding | Fasting on day 1 and 2. Time-course of plasma triacylglycerol concentrations in response to exercise and/or feeding on day 2. | Day 1 fasting. Day 2 fasting (0 hour point), 1.5hours, 1.75hours, 2hours, 3hours, 4hours, 5hours, 5.5hours, 5.75hours, 6hours, 7hours, 8hours and 9hours. | 
| Endothelial function changes in response to exercise and feeding | Changes in endothelial function via flow-mediated dilatation in response to feeding and exercise. | Day 1 fasting and 8.75hours. Day 2 fasting and 2.5hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose changes in response to exercise and/or feeding | Fasting on day 1 and 2. Time-course of plasma glucose concentrations in response to exercise and/or feeding on day 2. | Day 1 fasting. Day 2 fasting (0 hour point), 1.5hours, 1.75hours, 2hours, 3hours, 4hours, 5hours, 5.5hours, 5.75hours, 6hours, 7hours, 8hours and 9hours. | 
| Blood pressure changes in response to exercise and/or feeding | Changes in blood pressure (systolic and diastolic). | Day 1 fasting. Day 2 fasting (0 hour point) and 1hours, 2hours, 3hours, 4hours, 5hours, 6hours, 7hours, 8hours and 9hours. | 
| Total cholesterol | Fasting plasma total cholesterol on day 1 and day 2 of both trials. | Day 1 fasting. Day 2 fasting. | 
| Insulin changes in response to exercise and/or feeding | Fasting on day 1 and 2. Time-course of plasma insulin concentrations in response to exercise and/or feeding on day 2. | Day 1 fasting. Day 2 fasting (0 hour point), 1.5hours, 2hours, 4hours, 5hours, 5.5hours, 7hours, 8hours. | 
| High-density lipoprotein cholesterol | Fasting high-density lipoprotein cholesterol on day 1 and 2 of both trials. | Day 1 fasting. Day 2 fasting. | 
| Low-density lipoprotein cholesterol | Fasting low-density lipoprotein cholesterol on day 1 and 2 of both trials. | Day 1 fasting. Day 2 fasting. | 
| Non-esterified fatty acids changes in response to exercise and/or feeding | Fasting on day 1 and 2. Time-course of plasma non-esterified fatty acid concentrations in response to exercise and/or feeding on day 2. | Day 1 fasting. Day 2 fasting (0 hour point), 1.5hours, 2hours, 4hours, 5hours, 5.5hours, 7hours and 9hours. | 
| Interleukin-6 changes in response to exercise and/or feeding | Fasting on day 1 and 2. Time-course of plasma interleukin-6 concentrations in response to exercise and/or feeding on day 2. | Day 1 fasting. Day 2 fasting (0 hour point), 3hours, 6hours and 8hours. | 
| C-Reactive protein changes in response to exercise and/or feeding | Fasting on day 1 and 2. Time-course of plasma C-Reactive protein concentrations in response to exercise and/or feeding on day 2. | Day 1 fasting. Day 2 fasting (0 hour point), 3hours, 6hours and 8hours. | 
| Tumor Necrosis Factor concentrations | Fasting tumor necrosis factor on day 1 and 2 of both trials. | Day 1 fasting. Day 2 fasting. | 
| Peroxiredoxin-4 changes in response to exercise and/or feeding | Fasting on day 1 and 2. Time-course of plasma peroxiredoxin-4 concentrations across day 2 of both trials. | Day 1 fasting. Day 2 fasting (0 hour point), 3hours, 6hours and 8hours. | 
| Superoxide dismutase 3 | Fasting on day 1 and 2. Time-course of plasma Superoxide dismutase 3 concentrations across day 2 of both trials | Day 1 fasting. Day 2 fasting (0 hour point), 3hours, 6hours and 8hours. |