Polyphenols and Overfeeding (Poly-Nut)

Polyphenols: Protection From Overfeeding-induced Insulin Resistance?

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.

Study Overview

• Status: Completed
• Conditions: Overfeeding
• Intervention / Treatment: Dietary supplement: 2g of grape polyphenol extract; Dietary supplement: Dietary Supplement: 2g of placebo (lactose)

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Pierre-bénite, France, 69495
    • Rhône Alpes Human Nutrition Center (CRNH Rhône-Alpes)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Martine LAVILLE, MD, PhD, Rhône Alpes Human Nutrition Center (CRNH Rhône-Alpes)

Publications and helpful links

General Publications

• Bartova S, Madrid-Gambin F, Fernandez L, Carayol J, Meugnier E, Segrestin B, Delage P, Vionnet N, Boizot A, Laville M, Vidal H, Marco S, Hager J, Moco S. Grape polyphenols decrease circulating branched chain amino acids in overfed adults. Front Nutr. 2022 Oct 26;9:998044. doi: 10.3389/fnut.2022.998044. eCollection 2022.
• Segrestin B, Delage P, Nemeth A, Seyssel K, Disse E, Nazare JA, Lambert-Porcheron S, Meiller L, Sauvinet V, Chanon S, Simon C, Ratiney H, Beuf O, Pralong F, Yassin NA, Boizot A, Gachet M, Burton-Pimentel KJ, Vidal H, Meugnier E, Vionnet N, Laville M. Polyphenol Supplementation Did Not Affect Insulin Sensitivity and Fat Deposition During One-Month Overfeeding in Randomized Placebo-Controlled Trials in Men and in Women. Front Nutr. 2022 May 9;9:854255. doi: 10.3389/fnut.2022.854255. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 20, 2014
• First Posted (Estimate): May 23, 2014

Study Record Updates

• Last Update Posted (Actual): August 23, 2017
• Last Update Submitted That Met QC Criteria: August 22, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Energy expenditure; Insulin resistance; Insulin sensitivity; Stable isotopes; Overfeeding; Fat distribution; Lipid oxidation; Subcutaneous and visceral adipose tissue; Peripheral and hepatic insulin sensitivity; Muscle and subcutaneous adipose tissue gene expression
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: 2013-807