Body Weight and Vascular Function

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.


Eligibility Criteria:
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