The major objectives are to investigate if a prolonged exercise training program can lower the intrahepatic lipid content and can improve the metabolism of the liver in type 2 diabetic patients and patients with non-alcoholic fatty liver disease,…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Hepatic and hepatobiliary disorders
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are the differences in values for intrahepatic lipid
content and mitochondrial liver function from baseline to endpoint in the same
group, as well as the differences in effect of the intervention between the
different groups.
Secondary outcome
The secondary objective is to investigate if the beneficial effects of exercise
training on metabolic risk markers are dependent on the reduction of liver fat.
Furthermore, we will measure if the reduction of liver fat and improvement of
liver metabolism correlates with improvement of lipid metabolism in the
skeletal muscle.
Background summary
Due to the western lifestyle, correlated with a high calorie intake and low
physical activity, obesity is becoming a major health problem. All over the
world obesity reaches epidemic proportions. Obesity is closely linked to type 2
diabetes, a multi-factorial disease that increases the presence of multiple
health problems. Until now, exercise and dietary intervention seem to be the
single most effective interventions to treat obesity and type 2 diabetes
mellitus. In obesity and type 2 diabetes, not only fat accumulation in adipose
tissue, but also fat accumulation in the peripheral tissues occurs. Fat
accumulation in peripheral tissues has been associated with insulin resistance.
Exercise seems to have a positive effect on the accumulation of fat in the
peripheral tissue and on the insulin sensitivity in type 2 diabetic patients.
Study objective
The major objectives are to investigate if a prolonged exercise training
program can lower the intrahepatic lipid content and can improve the metabolism
of the liver in type 2 diabetic patients and patients with non-alcoholic fatty
liver disease, and to examine if this leads to improvements in metabolic risk
markers. To this end, we will include investigation of the effect of exercise
on adipose tissue (inflammatory markers and adipocyte size) and skeletal muscle
(ex vivo lipid metabolism) to incorporate the effect of exercise on liver,
muscle and adipose tissue and to clarify the crosstalk between these tissues in
the pathophysiology of type 2 diabetes.
Study design
Thirty-eight type 2 diabetic patients, 38 non-alcoholic fatty liver patients
and 38 matched controls will follow a 12 weeks exercise-training program. Two
times a week they will perform an aerobic cycling training and once a week
resistance training. Before onset and after the training period body
composition (DEXA), endothelial wall function (RH- PAT), cardiac lipid
(1H-MRS), cardiac function (Ultrasound), liver mitochondrial function (MBT),
liver metabolism (31P-MRS), maximal aerobic capacity (VO2max), maximal
voluntary contraction, intrahepatic lipid (1H-MRS) and insulin sensitivity
(hyperinsulinemic- euglycemic clamp) will be measured.
Intervention
Subjects will undergo a 12 weeks exercise intervention, which consist of 2
times a week an aerobic exercise and 1 time per week resistance training.
Study burden and risks
Blood drawing and the placement of several cannulas can cause a bruise.
Furthermore, the training-intervention can lead to mild muscle pain and
stiffness. There can be coincidental findings due to the MRS measurements (=
*toevalsbevindingen*) and there is radiation exposure due to DEXA measurements
(0.001 mSv/time).
Three days prior to the clamp diabetic subjects will have to stop their
anti-diabetic medication. This may cause an increase in blood glucose levels.
Subjects will receive a one-touch blood glucose meter to determine their fasted
blood glucose levels in the 3 days before the 3rd post-intervention test day.
If their fasted blood glucose levels are higher than 13.0 mmol/l, they will
need to contact the principal investigator. He will decide to restart the
anti-diabetic medication and to exclude the subjects of the study.
A muscle biopsy can lead to a painful bruise and muscle pain on the place the
biopsy was taken. To limit these risk as much as possible, a bandage will be
placed and subjects will have to wear it for at least 24 hours. Intense
exercise will be discouraged for the next 24 hours. Bruises disappear after
some days. An experienced medical doctor will take muscle biopsies.
Due to local anesthesia, the adipose tissue biopsy is painless. To minimize the
risk for a hematoma, the adipose tissue biopsy place will be compressed for
approximately 5 minutes after biopsy. The place of incision will leave a small
scar (~ 3 mm). To promote good wound healing, the incision will be sealed with
sterile steri-strips and a waterproof band-aid.
Universiteitssingel 50
Maastricht 6200MD
NL
Universiteitssingel 50
Maastricht 6200MD
NL
Listed location countries
Age
Inclusion criteria
All subjects:
Male sex
Age 40-70 years
BMI 27-35 kg/m2
Stable dietary habits
sedentary: no participation in any kind of sports for at least 2 years
For diabetic patients only:
Must be on sulphonylurea or metformin therapy for at least 6 months with constant dose for at least 2 months, or on a dietary treatment for at least 6 months
Well-controled diabetes: fasting plasma glucose concentration * 7.0 mmol/l and < 10.0 mmol/l at the time of screening.;For subjects with non-alcoholic fatty liver disease:
Liver fat content * 5,56%
Fasting plasma concentration must be < 7.0 mmol/l ;For control subjects:
Liver fat content < 5,56%
Normoglycemic according to the WHO criteria (OGTT)
Exclusion criteria
Female sex
Unstable body weight (weight gain or loss > 3 kg in the past three months)
Participation in an intensive weight-loss program or in a exercise program during
the last year before the start of the study.
(Low) physical activity (more than 30 minutes (low) physical activity per week)
Active cardiovascular disease. (This will be determined by quenstionnaires and by screening on medication. Furthermore, all subjects
will undergo a physical examination by a medical doctor).
Chronic renal dysfunction (creatinine > 2 increased (normal values: 64-104 µmol/l))
Use of Beta-blockers
Systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg
Haemoglobin < 7.5 mmol/l (anemia)
Blood donor
Use of medication know to interfere with glucose homeostasis (i.e. corticosteroids), except for diabetics
Use of anti-trombotic medication
Claustrophobia and metal implants (with respect to MRI)
Abuse of drugs
Participation in another biomedical study within 1 month before the first screening
visit
Alcohol abuse (> 3 units (1unit = 10 gram ethanol) per day);For diabetic patients:
Severe diabetes which requires application of insulin or patients with diabetes-related complications;For controls:
Liver disease or liver dysfunction (ALAT > 2.5 x increased (normal values: 5 - 60 U/L))
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 |
|---|---|
| ClinicalTrials.gov | NCT01317576 |
| CCMO | NL34882.068.10 |