Lipid Metabolism Disorder
Conditions
Brief summary
The present research protocol will analyze whether a short-term modification (one week) of dietary habits would have an impact on the postprandial metabolism of dietary fatty acids and on their uptake by non-adipose tissues, in healthy subjects. Each subject will participate in two protocols randomly determined and separated by a period of one month: a 7-day isocaloric diet (Protocol A) and a 7-day carbohydrate-rich diet containing +50% of the subject's energy needs. (Protocol B). At the end of each diet, the subject will go through a postprandial metabolic study of 8 hours where different parameters will be measured thanks to PET imaging and perfusions of stables isotopes.
Interventions
DIETARY_SUPPLEMENTisocaloric diet
a 7-day isocaloric diet
DIETARY_SUPPLEMENTHypercaloric diet
A 7-day hypercaloric diet supplemented with carbohydrate-rich food (+ 50% of the subject's energy needs).
OTHERLiquid meal
RADIATIONPET imaging
OTHERperfusions of stable tracers
DEVICEIndirect calorimetry
Sponsors
Hospices Civils de Lyon
Université de Sherbrooke
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy subjects: subjects with normal glucose tolerance determined according to an oral glucose tolerance test and with a BMI above 25 kg/m2 without first degree of familial history of type 2 diabetes (parents, siblings).
Exclusion criteria
* overt cardiovascular disease as assessed by medical history, physical exam, and abnormal ECG * treatment with a fibrate, thiazolidinedione, beta-blocker or other drug known to affect lipid or carbohydrate metabolism (except statins, metformin, and other antihypertensive agents that can be safely interrupted) * presence of liver or renal disease, uncontrolled thyroid disorder, previous pancreatitis, bleeding disorder, or other major illness * smoking (\>1 cigarette/day) and/or consumption of \>2 alcoholic beverages per day * prior history or current fasting plasma cholesterol level \> 7 mmol/l or fasting TG \> 5 mmol/l * any other contraindication to temporarily interrupt current meds for lipids or hypertension * being pregnant * not be barren
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| whole-body organ-specific Dietary Fatty Acid (DFA) partitioning | 2 months | will be determined by whole-body CT (16 mA) followed by PET acquisition of 18FTHA |
| Left ventricular function by Positron Emiting Positron (PET) ventriculography | 2 months | will be determined using 11C-acetate PET/CT. 180 MBq will be administered by bolus injection at fasting. After a transmission scan and regional CT (40mA), a 30-min dynamic list-mode PET acquisition will be performed on a 18 cm-high thoraco-abdominal segment to include the left cardiac ventricle and most of the liver on a Philips Gemini TOF PET/CT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac and hepatic blood flow | 2 months | will be determined using 11C-acetate PET/CT followed by a 30 minutes dynamic PET acquisition.. |
| metabolites appearance rate | 6 months | will be determined by perfusion of stable isotope tracers |
| energy metabolism (whole body production) | 4 months | by indirect calorimetry |
| hormonal responses | 4 months | analysed by colorimetric and Elisa tests |
| Cardiac DFA uptake | 2 months | will be assessed using PET/CT method with oral administration of 18FTHA followed by a 30 min. dynamic PET acquisition |
| Insulin secretion rate | 4 months | will be assessed using deconvolution of plasma C-peptide with standard Cpeptide kinetic parameters |
| β-cell function | 4 months | will be assessed by calculation of the disposition index (DI) that is insulin secretion in response to the ambient insulin |
| Anthropometric parameters | 2 months | will be measured at each postprandial metabolic study |
| Insulin sensitivity | 4 months | will be determined using the HOMA-IR (based on fasting insulin and glucose) levels |
| Cardiac and hepatic oxidative metabolism index | 2 months | will be determined using 11C-acetate PET/CT followed by a 30 minutes dynamic PET acquisition. |
Countries
Canada
Outcome results
None listed