Polyphenols and Overfeeding

Study Overview
=================
Brief Summary
-----------------
Obesity is a complex and multifactorial disease representing a major public health challenge. Indeed, overweight and obese people carry a major risk of developing insulin resistance and type 2 diabetes mellitus. It has been demonstrated that polyphenols could be used to counteract some of the mechanisms involved in the generation of insulin resistance. The model of overfeeding represents a very good study model of the metabolic complications of obesity, since it has been shown to induce a transient state of insulin resistance in the human. The purpose of this research is to study the effects of a overfeeding (+50% of daily caloric needs over 31 days) with or without polyphenols supplementation (2g/days over 31 days) on insulin sensitivity measured in the setting of a hyperinsulinemic euglycemic clamp and on post prandial partitioning of exogenous lipids after a test meal. During 31 days, the volunteers will consume chocolate bars, chips, chocolate breads and cola in addition to their usual diet and will be supplemented with 2g of grape polyphenols extract or with placebo.

Official Title
-----------------
Polyphenols: Protection From Overfeeding-induced Insulin Resistance?

Conditions
-----------------
Overfeeding

Intervention / Treatment
-----------------
* Dietary Supplement: 2g of grape polyphenol extract
* Dietary Supplement: Dietary Supplement: 2g of placebo (lactose)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male Aged from 18 to 55 years Body Mass Index of 23 to 27 kg/m² Normal blood pressure Fasting glycemia < 7 mmol/L CRPus < 10mg/L Triglycerides ≤ 3mmol/L Exclusion Criteria: Medical or surgical history which may affect the results (renal -cardiovascular - hepatic- endocrine-inflammatory diseases) Subjects under treatment which may interfere with the measured parameters Eating disorder Intensive sportive activity Dairy products allergy or intolerance

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2g of grape polyphenol extract supplement<br>Men will have to consume daily 2g of grape polyphenol extract during the 31 days of overfeeding. | Dietary Supplement: 2g of grape polyphenol extract<br>* Men will have to consume daily 2g of grape polyphenol extract during the 31 days of overfeeding.<br>|
| Placebo Comparator: 2g of placebo (lactose)<br>Men will have to consume daily 2g of placebo during the 31 days of overfeeding. | Dietary Supplement: Dietary Supplement: 2g of placebo (lactose)<br>* Men will have to consume daily 2g of placebo during the 31 days of overfeeding.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral insulin sensitivity | Volunteers will have peripheral and hepatic insulin sensitivity determined by using a two-stage hyperinsulinemic euglycemic clamp with stable isotopically labeled tracer infusion. | During 31 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic insulin sensitivity | Endogenous glucose production (EGP) will be determined during the last 30 minutes of the low-dose insulin infusion. | before and after the 31 days of overfeeding | 
| Change in genes expression in adipose and muscle tissues | RT-PCR | Before and after the 31 days of overfeeding | 
| Anthropometry, Fat quantification and Abdominal fat distribution | Weight, height, waist and hip circumferences, fat mass using dual x-ray absorptiometry (DEXA) and abdominal fat distribution using resonance magnetic imaging (RMI). | During 31 days | 
| Fasting and Postprandial partitioning of exogenous lipid | 13C enrichment will be measured in blood samples and breath test during a test meal performed before and after the 31 days of overfeeding. | Fasting and during all the postprandial period (0-300 minutes) | 
| Modification in intestinal microbiota | Feces analyses | Before and after the 31 days of overfeeding | 
| Energy expenditure and substrate oxidation with indirect calorimetry | Energy metabolism will be measured before and after the 31 days of overfeeding. | Fasting and during all the postprandial period (0-300 minutes) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Insulin sensitivity, Overfeeding, Fat distribution, Subcutaneous and visceral adipose tissue, Insulin resistance, Peripheral and hepatic insulin sensitivity, Stable isotopes, Lipid oxidation, Energy expenditure, Muscle and subcutaneous adipose tissue gene expression