Body Weight and Vascular Function

Study Overview
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Brief Summary
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An increased body mass impairs vascular function (VF), an important characteristic of subjects suffering from type 2 diabetes and a risk marker for cardiovascular diseases. However, a wide variety of in vivo VF markers exists each measuring different aspects of VF. Each of these markers addresses a different aspect of the vasculature. Studies comparing under standardized conditions the differences and relationships of the many different VF measurements in lean and abdominally overweight / obese subjects are missing. Also, there is a great need to know which of these markers are sensitive to dietary challenges. Therefore, it is imperative to conduct an extensive study on dietary effects and interrelationships of a broad spectrum of VF measurements and plasma biomarkers in lean and overweight / obese subjects. Focus will be on FMD, a well accepted biomarker for cardiovascular disease. The investigators propose to examine, in a two-way parallel-randomized human intervention study, the effects of weight-loss in abdominally overweight / obese men on VF markers and plasma biomarkers related to low-grade inflammation and vascular activity during the fasting and both the postprandial and hyperinsulinemic state. Furthermore, differences - and relations between - VF measurements and plasma biomarkers will be compared cross-sectionally between lean and abdominally overweight / obese male subjects.

Official Title
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Vascular Function Markers: Differences Between Lean and Abdominally Overweight / Obese Men and Effects of Weight Loss

Conditions
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Metabolic Syndrome, Obesity

Intervention / Treatment
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* Other: Weight-loss treatment
* Other: No-weight loss treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 65 years Waist circumference below 94 cm (lean subjects) or between 102 - 110 cm (abdominally overweight / obese subjects) Caucasian Plasma glucose < 7.0 mmol/L Serum total cholesterol < 8.0 mmol/L Serum triacylglycerol < 4.5 mmol/L Plasma HbA1c < 6.5% No current smoker No diabetic patients No familial hypercholesterolemia No abuse of drugs Less than 14 alcoholic consumptions per week Stable body weight (weight gain or loss < 3 kg in the past three months) No use of medication known to affect blood pressure, serum lipid or glucose metabolism No severe medical conditions that might interfere with the study, such as epilepsy, asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis No active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident No contra-indications for MRI imaging Willingness to give up being a blood donor (or having donated blood) from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study No difficult venipuncture as evidenced during the screening visit Exclusion Criteria: Women Non-caucasian Plasma glucose ≥ 7.0 mmol/L Serum total cholesterol ≥ 8.0 mmol/L Serum triacylglycerol ≥ 4.5 mmol/L Plasma HbA1c ≥ 6.5% Current smoker, or smoking cessation < 12 months Diabetic patients Familial hypercholesterolemia Abuse of drugs More than 14 alcoholic consumptions per week Unstable body weight (weight gain or loss > 3 kg in the past three months) Use of use of medication known to affect blood pressure, serum lipid or glucose metabolism Severe medical conditions that might interfere with the study, such as epilepsy, asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident Contra-indications for MRI imaging Use of an investigational product within the previous 1-month Not willing to give up being a blood donor (or having donated blood) from 8 weeks before the start of the study, during the study or for 4 weeks after completion of the study Not or difficult to venipuncture as evidenced during the screening visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weight-loss treatment<br>A very-low energy diet (Modifast Intensive) for 4-5 weeks providing 2.1 MJ/day in order to reduce body weight. After 4-5 weeks a mixed solid energy-restricted diet up to 4.2 MJ/day with a recommended composition for the following 1-2 weeks. Then, a diet matching their energy requirements to maintain newly achieved body weights (weight-stable conditions) for at least 2 weeks. | Other: Weight-loss treatment<br>* A very-low energy diet (Modifast Intensive) for 4-5 weeks providing 2.1 MJ/day in order to reduce body weight. After 4-5 weeks a mixed solid energy-restricted diet up to 4.2 MJ/day with a recommended composition for the following 1-2 weeks. Then, a diet matching their energy requirements to maintain newly achieved body weights (weight-stable conditions) for at least 2 weeks.<br>|
| Other: No-weight loss treatment<br>Maintenance of habitual diet and physical activity for 8 weeks to maintain body weights. | Other: No-weight loss treatment<br>* Maintenance of habitual diet and physical activity for 8 weeks to maintain body weights.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular activity: differences between lean and abdominally overweight / obese men and effects of weight loss | Flow-mediated dilation (FMD) of the brachial artery. | Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline at 2 hours after meal consumption | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular function markers related to the macrovasculature: differences between lean and abdominally overweight / obese men and effects of weight loss | Carotid-wall intima-media thickness (IMT), carotid compliance and distensibility, pulse wave velocity and analysis (PWV and PWA) and peripheral artery tonometry (PAT). | Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 2 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp) | 
| Vascular function markers related to the microvasculature: differences between lean and abdominally overweight / obese men and effects of weight loss | Capillary video microscopy of the finger skin, skin microvascular vasomotion, glycocalyx thickness, retina photography, skin auto fluorescence and contrast enhanced ultrasound (CEUS) in skeletal muscle. | Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 1 and 3 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp) | 
| Metabolic risk markers related to the metabolic syndrome: differences between lean and abdominally overweight / obese men and effects of weight loss | Biomarkers for low-grade inflammation and endothelial activation. | Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (during 4 hours after meal consumption) / hyperinsulinemic state (during 3 hours after initiation of the clamp) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Weight Loss, Vascular Function Markers, Body Weight