The main objective is to elucidate the acute effects of an oral intake of either saturated, monounsaturated or polyunsaturated fatty acids on PBMC whole genome expression of obese and type 2 diabetic obese subjects. Secondary objectives are to…
ID
Source
Brief title
Condition
- Other condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Health condition
obese en gezonde vrijwilligers
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PBMC gene expression profiles
Secondary outcome
PBMC inflammatory response capacity
Endothelial function
Tertiar:
lipid profiles
plasma glucose and insulin
monocyte and lymfocyte gene expression profiles
Background summary
Consumption of high-fat diets can lead to postprandial dyslipidemia, impairment
of endothelial function, activation of immune cells and changes in gene
expression profiles of immune cells such as peripheral blood mononuclear cells
(PBMC).
Recently it was shown that postprandial gene expression profiles of PBMC and
plasma triglyceride (TG) and free fatty acid (FFA) responses are dependent on
the type of dietary fat consumed (i.e. saturated, monounsaturated and
polyunsaturated). Since obese and diabetic subjects usually are in a
pro-inflammatory state and have dyslipidemia and endothelial dysfunction we are
interested in the effect of different fatty acids in a high load on the PBMC
gene expression profiles, plasma cytokine profiles and endothelial function of
these subjects.
Study objective
The main objective is to elucidate the acute effects of an oral intake of
either saturated, monounsaturated or polyunsaturated fatty acids on PBMC whole
genome expression of obese and type 2 diabetic obese subjects.
Secondary objectives are to elucidate the acute effects of the fat loads on
PBMC inflammatory response capacity and endothelial function of these subjects.
Tertiary objectives are to investigate the effects of the fat loads in the
groups of subjects on plasma lipid profiles, plasma glucose and insulin and on
monocyte and lymphocyte whole genome expression.
Study design
Single blind cross-over intervention
Intervention
Elke participant will consume 3 high-fat milkshakes differering in fatty acid
composition (saturated fat, monounsaturated fat and polyunsaturated fat)
Study burden and risks
During a screening visit 3 ml blood will be drawn and urine will be collected
after a overnight fast and body weight, length, waist and blood pressure will
be measured. An oral glucose tolerance test will be performed. A general and
medical questionnaire will be used.
During the study period of 8 weeks each participant will visit the university
on 3 mornings, separated by at least one week, and will consume within 15
minutes a milkshake containing 95 grams of fat. Blood will be collected and
endothelial function will be measured both before consuming the milkshakes
(baseline, T=0) and 2 hrs (T=2) and 4 hrs (T=4) after consumption of the
shakes. Blood will be drawn by normal venopuncture. At time points 0 and 2 hrs
60 ml blood will be collected and at time point 4 hr 52 ml will be collected,
bringing it to a total of 172 ml per day. Hb values of each participant will be
monitored during the study to be sure that blood collection will not lead to
anaemia.
Participants have to collect a small amount of faeces at one time point during
the study period. The body composition of the participants will be measured in
the Bod Pod. In addition, the participants will visit the radiology department
of the hospital Gelderse Vallei in Ede for a MRI scan to determine their
abdominal bodyfat distribution.
The time investment requested from the participants is 1 hour at the
information meeting, 2.5 hours at a screening session, 3 x 4.5 hours at the
intervention days and 1 hour for the MRI scan. The risks associated with venous
blood drawing by venopuncture are minimal. The consumption of the milkshakes is
not expected to be associated with discomfort, but could, in rare cases, have
adverse effects such as a mild gastrointestinal discomfort (fishy aftertaste in
case of PUFA shake, belching, flatulence or loose stools). MRI is a safe
procedure, with no known health risk as long as no contraindication is met (see
paragraph 9.4.3). MRI can result in a *coincidence* finding. These findings
should be reported and subjects will be informed about this.
Bomenweg 2
6703 HD Wageningen
Nederland
Bomenweg 2
6703 HD Wageningen
Nederland
Listed location countries
Age
Inclusion criteria
Inclusion criteria for all participants:
- male gender
-50-70 yrs
For diabetic patients only:
- BMI >30 kg/m2
- Well-controlled diabetes: fasting plasma glucose concentration must be <10.0 mmol/l at the time of screening.
- Must be on sulphonylurea- or metformin therapy for at least 6 months with a constant dose for at least two months, or on dietary treatment for at least 6 months2.
For obese controls only:
- BMI > 30 kg/m2
- normoglycemic according to WHO criteria (OGTT, fasting blood glucose< 7 mmol/L, after 2 hr <7.8mmol/L)
For lean controls only:
- BMI 18-25 kg/m2
- normoglycemic according to WHO criteria (OGTT, fasting blood glucose< 7 mmol/L, after 2 hr <7.8mmol/L)
Exclusion criteria
Exclusion criteria for all participants:
All subjects:
- Female gender
- Age below 50 or above 70 years
- Hemoglobin levels <8.4 mmol/L
- Allergic to cow milk or dairy products
- Allergic to fish oil
- Vegetarian
- Tobacco smoker
- Current or recent (<4 weeks) use of fish oil supplements or more then four times fish/week; 24.35 g of EPA-DHA of fish per month (800 mg/day) as judged by the questionnaire.
- Received inoculations within 2 months of starting the study or planned to during the study
- Donated or intended to donate blood from 2 months before the study till two months after the study
- Unstable body weight (weight gain or loss > 3 kg in the past three months)
- Medical condition that can interfere with the study outcome (i.e. cardiovascular disease, gastrointestinal disease, renal dysfunction)
- Use of medications know to interfere with glucose homeostasis (i.e. corticosteroids)
- abuse of drugs and/or alcohol
- participation in another biomedical study within 1 month before the first screening visit;For obese, type 2 diabetic subjects only:
- severe diabetes which requires application of insulin
- diabetes-related complications
For obese subjects and lean controls only:
- hyperglycemic according to WHO criteria (OGTT, fasting blood glucose >6.0mM, after 2 hr>11mM)
-systolic blood pressure >160 mmHg or diastolic blood pressure > 100 mmHg
- Urinary glucose concentrations (>0.25 g/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 |
|---|---|
| CCMO | NL28001.081.09 |