Effect of a Carbohydrate-rich Diet in Healthy Subjects

Study Overview
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Brief Summary
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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.

Official Title
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The Relative Contribution of Dietary Lipids vs. of Fatty Acids to Non-adipose Tissues and the Effect of a Carbohydrate-rich Diet in Healthy Subjects

Conditions
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Lipid Metabolism Disorder

Intervention / Treatment
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* Dietary Supplement: isocaloric diet
* Dietary Supplement: Hypercaloric diet
* Other: Liquid meal
* Radiation: PET imaging
* Other: perfusions of stable tracers
* Device: Indirect calorimetry


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Isocaloric diet (7 days)<br>Protocole A | Dietary Supplement: isocaloric diet<br>* a 7-day isocaloric diet<br>Other: Liquid meal<br> <br> Radiation: PET imaging<br> <br> Other: perfusions of stable tracers<br> <br> Device: Indirect calorimetry<br> <br> |
| Experimental: Hypercaloric diet enriched with carbohydrate food (7 days)<br>Protocole B | Dietary Supplement: Hypercaloric diet<br>* A 7-day hypercaloric diet supplemented with carbohydrate-rich food (+ 50% of the subject's energy needs).<br>Other: Liquid meal<br> <br> Radiation: PET imaging<br> <br> Other: perfusions of stable tracers<br> <br> Device: Indirect calorimetry<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| whole-body organ-specific Dietary Fatty Acid (DFA) partitioning | will be determined by whole-body CT (16 mA) followed by PET acquisition of 18FTHA | 2 months | 
| Left ventricular function by Positron Emiting Positron (PET) ventriculography | 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 | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac DFA uptake | will be assessed using PET/CT method with oral administration of 18FTHA followed by a 30 min. dynamic PET acquisition | 2 months | 
| Cardiac and hepatic oxidative metabolism index | will be determined using 11C-acetate PET/CT followed by a 30 minutes dynamic PET acquisition. | 2 months | 
| Cardiac and hepatic blood flow | will be determined using 11C-acetate PET/CT followed by a 30 minutes dynamic PET acquisition.. | 2 months | 
| metabolites appearance rate | will be determined by perfusion of stable isotope tracers | 6 months | 
| energy metabolism (whole body production) | by indirect calorimetry | 4 months | 
| hormonal responses | analysed by colorimetric and Elisa tests | 4 months | 
| Insulin sensitivity | will be determined using the HOMA-IR (based on fasting insulin and glucose) levels | 4 months | 
| Insulin secretion rate | will be assessed using deconvolution of plasma C-peptide with standard Cpeptide kinetic parameters | 4 months | 
| β-cell function | will be assessed by calculation of the disposition index (DI) that is insulin secretion in response to the ambient insulin | 4 months | 
| Anthropometric parameters | will be measured at each postprandial metabolic study | 2 months |