The major research objective is:Does a switch from a low-fat to a high-fat diet lead to a reduced hepatic and skeletal muscle insulin sensitivity due to an increase lipid accumulation in liver, skeletal muscle and heart? Secondary research…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameter is the difference in insulin sensitivity after a switch
from a low-fat diet to a high-fat diet compared to the control group, which
stays on a low-fat diet.
Secondary outcome
As secondary endpoints differences in lipid accumulation in heart liver and
muscle, cardiac function, the time-course of lipid accumulation and the
relationship between the tissue parameter lipid accumulation and the functional
outcome parameter insulin resistance are considered.
Background summary
Intramyocellular lipid (IMCL), Intrahepatic lipid (IHL) and Intracardiac lipids
(ICL) are important features of the metabolic syndrome and its complications.
Although, it is known that diet can influence IMCL and IHL in rodents and in
humans, the time-course of peripheral lipid accumulation and its relationship
with tissue specific insulin while switching from a low-fat to a high-fat diet
is unknown. Also the relationship between cardiac lipid accumulation and
cardiac function is unknown.
Study objective
The major research objective is:
Does a switch from a low-fat to a high-fat diet lead to a reduced hepatic and
skeletal muscle insulin sensitivity due to an increase lipid accumulation in
liver, skeletal muscle and heart?
Secondary research objectives are:
o Does a switch from a low-fat to high-fat diet lead to lipid accumulation in
liver, heart and muscle
o To establish the time-course of lipid accumulation in liver following a
short-term dietary intervention
o To establish the relationship between the tissue parameter lipid accumulation
and the functional outcome parameter insulin resistance
o To establish the relationship between cardiac lipid accumulation and cardiac
function.
Study design
In this project we will examine the effect of an increase in dietary fat intake
on intrahepatic, intramyocellular and intracardiac lipid accumulation in
relation to insulin sensitivity and cardiac function. Basal measurements will
be made after a 3-week low-fat diet (run-in), after which half of the subjects
will switch to a 3 week high-fat diet (experimental group), and half of the
subjects will remain on the low-fat diet (control group).
The low-fat diet which will deliver 15 Energy% of energy as protein, 65 En% as
CHO and 20 En% as fat. The high-fat diet will consist of 15 En% protein, 30 En%
CHO and 55% En% fat).
Study burden and risks
Before the start of the study subjects will be screened to access eligibility
(visit duration: 30 min). After screening also body composition and maximal
endurance capacity will be measured (60 min)
Subsequent each subject will be randomly allocated to the control or the
experimental group. The subjects will visit the department 4 (control group:
day 0-21-28-42) or 6 times (experimental group: day 0-20-21-28-41-42) during
the 6-weeks study period. During these visits two blood samples, two
hyperinsulinemic-euglycemic clamps, including 2 muscle biopsies during each
clamp, will be performed; 5 MRS-sessions will take place in the experimental
group and 2 MRS-sessions in the control.
Venapuncters and muscle biopsies can cause local hematomas; the muscle biopsy
can result in some discomfort the day after.
Universiteitssingel 50
6200 MD
Nederland
Universiteitssingel 50
6200 MD
Nederland
Listed location countries
Age
Inclusion criteria
• Male sex
• Age 18-65 years
• BMI 25-35 kg/m2
• Sedentary
• Stable dietary habits
• Healthy
• Not wanting to be informed about a conincedence finding.
Exclusion criteria
• Current use of medication that is known to interfere with the results of the study.
• Consuming more than 20 g of alcohol per day (± 2 units)
• Serum-γ-glutamyltranspeptidase level > 70 IU/L
• A history of cardiovascular disease like congestive heart failure or acute myocardial infarction
• Plasma triacylglycerol > 4.5 mmol/L
• Familial hypercholesterolemia
• A history of liver disease
• Unstable body weight (weight gain or loss > 3 kg in the past three months)
• Abuse of drugs
• Participation in another biomedical study within 1 month prior to the screening visit
• Impossible or difficult venipuncture during screening
• a fasting glucose above 7.0 mmol/L
• a contraindication to MRI scanning. These contraindications include patients with the following devices:
o Central nervous system aneurysm clips;
o Implanted neural stimulator;
o Implanted cardiac pacemaker or defibrillator;
o Cochlear implant;
o Ocular foreign body (e.g. metal shavings);
o Insulin pump;
o Metal shrapnel or bullet;
o Or metal containing corpora aliena in the eye of brains
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 | NL16162.068.07 |