We hypothesize that the amount of physical activity correlates with insulin-induced microvascular recruitment during free-fatty acid infusion in skeletal muscle as well as in the heart. In this study we aim to test this hypothesis.
ID
Source
Brief title
Condition
- Myocardial disorders
- Glucose metabolism disorders (incl diabetes mellitus)
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The effect of FFA on insulin-induced changes in microvascular blood volume of
skeletal muscle and myocardium will be correlated with amount of physical
activity as measured with accelerometers and VO2max.
Secondary outcome
Secundary endpoints will be microvascular blood volume during basal and
hyperinsulinemic state without Intralipid infusion, in myocardium and skeletal
muscle. Also, whole-body insulin sensitivity as measured by the glucose
infusion rate will be correlated with physical activity. Body fat percentage
and blood pressure (Nexfin) will be measured to test if these parameters are
equal between subjects and if not in which amount they differ. Contraction
induced microvascular recruitment will be measured with the handgrip
dynamometer to test if we can show an increase of MBV with Ceus during a
different physiological parameter than insulin alone.
Background summary
Physical activity lowers the risk of ischemic heart disease and type 2
diabetes, but the mechanisms by which physical activity exerts these effects
are incompletely understood. Excess of free fatty acids (FFA) is shown to be a
key factor in the development of insulin resistance and a reduced dilatory
response of arterioles and subsequent decrease of microvascular recruitment to
insulin, also referred to as vascular insulin resistance, has been suggested to
play a role in ischemic heart disease. Acute exposure to FFA impairs whole body
insulin sensitivity and physical activity has been shown to prevent this
effect. Insulin-induced microvascular recruitment in both skeletal muscle and
heart are also impaired after acute FFA infusion, but the effect of physical
activity has not been investigated. An improved response to FFA of the
microvasculature in skeletal muscle could potentially protect against insulin
resistance and a similar effect in the heart could reduce risk of developing
ischemic heart disease.
Study objective
We hypothesize that the amount of physical activity correlates with
insulin-induced microvascular recruitment during free-fatty acid infusion in
skeletal muscle as well as in the heart. In this study we aim to test this
hypothesis.
Study design
We will test healthy subjects. We will study whole-body insulin sensitivity and
insulin-induced microvascular recruitment by contrast ultrasonography in
skeletal muscle and myocardium before and after iv. FFA infusion and measure
physical activity with accelerometers and vo2max.
Study burden and risks
After application subjects will be selected based on a short history taking by
telephone.
After inclusion, the subjects will be visiting the clinical research unit once.
They will undergo basic examination including measurement of length, body
weight, blood pressure and plasma glucose to make sure the subject*s health
status is in agreement with the history provided by telephone. Next, subjects
will undergo a hyperinsulinemic-euglycemic clamp, with microvascular contrast
ultrasonography measurements of the skeletal muscle and the heart. Risks
associated with these measurements consist of risk of hypoglycemia or
hyperglycaemia during hyperinsulinemic-euglycemic clamp, headache, nausea,
transient pulmonary hypertension and allergic reactions during contrast
ultrasonography (rare). Bruising and local pain in the antecubital fold may be
experienced during and after placement of venous catheters and/or during blood
sampling. As a compensation for their time and effort subjects will receive ยค85
after completion of the investigation. Burden and risk of participation are
very limited.
Risk of VO2 max measurements in these healthy subjects is very small, but
include myalgia because of the exercise and a very small risk of syncope.
In addition, we would like to perform a pilot in 10 participants to optimise
the contrast ultrasonography protocol. This pilot protocol will take 45
minutes. Risks and burden for the participants are very limited.
Van der Boechorststraat 7
Amsterdam 1081 BT
NL
Van der Boechorststraat 7
Amsterdam 1081 BT
NL
Listed location countries
Age
Inclusion criteria
Young healthy male subjects. Age 18-30 years.
Exclusion criteria
A drastic recent change in physical activity (eg. just stopped being an athlete), conditions that can significantly influence the amount of energy that is needed for physical activity (eg. a lower-leg prothesis), history of obesity, hypertension, diabetes mellitus, hyperlipidemia, smoking (currently, or > 1 package per month over the last 2 years), documented cardiovascular disease, use of medication that could potentially affect insulin sensitivity or microvascular function or inflammatory status.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL53462.029.15 |