Assessing the Value of Red Grapes Polyphenol Supplementation on Metabolic Parameters in Obese Insulinoresistant Subjects
Condition: Obesity; Insulin Resistance; Menopause
MeSH terms: Insulin Resistance
Study type: Interventional

Summary: 
      Obesity, chronic disease, is a real public health problem because of its high prevalence but
      also because of the high risk of complications, including insulin resistance (IR) and type 2
      diabetes (T2D). The mechanisms involved in the development of IR are not well known.
      Oxidative stress and inflammation induced by food overload could be the initiators IR
      mechanisms in skeletal muscle, responsible for the use of nearly 80% glucose in response to
      insulin and therefore plays a major role in the regulation of glucose metabolism. Thus, an
      increase in ROS (Reactive Oxygen Species), markers of oxidative stress and chronic low-grade
      inflammation have been demonstrated in subjects with obesity, the latter decreasing in weight
      loss. Therapeutically, loosing weight is still very difficult these days, because of the
      complexity of this chronic disease. Thus, it is well established that restrictive diets to
      expose weight rebound, dramatic medically as in human terms for these patients. Support for
      physical activity is also difficult because of reduced mobility in patients, refer to the
      lack of motivation among some. Finally, investigators have no treatment "against-obesity" who
      have demonstrated a benefit / risk enough to be used routinely. It is therefore essential to
      seek other means of struggle against the IR, see help in weight loss.

      In parallel, it is well established that the consumption of certain antioxidants, including
      polyphenols (PP) grape as extracts and whole foods, modulates favorably several pathways
      responsible for the development of IR in cell models animals. The results of antioxidants
      supplementation in humans are few and controversial. However, most supplementation studies in
      human used a PP, Resveratrol at supra nutritional doses (ie not compatible with a balanced
      diet of fruits and vegetables). In a previous study, investigators tested the interest of a
      supplementation with red grape PP nutritional doses in healthy subjects with metabolic risk
      (overweight subjects and related to the first degree of T2DM patients) on IR hyperinsulinemic
      euglycemic clamp measured. During this study, the PP have prevented the central mechanisms of
      muscle IR that are oxidative stress and mitochondrial dysfunction induced by a load fructose.

      For this project, investigators propose to test the effect of a red grape PP supplementation
      at nutritional doses for 8 weeks on IR and weight loss in 30 obese insulin resistant. This is
      a double-blind randomized placebo-controlled. This supplementation will be associated with a
      standard support for their obesity performed routinely in the Nutrition and Diabetes unit.

      Specific inclusion criteria: Female or male nondiabetic 50-65 years, BMI> 30 kg / m2 and with
      a HOMA> 3.

      The main objective is to test whether supplementation PP improves systemic insulin
      sensitivity (GIR: rate glucose infusion) measured by hyperinsulinemic-euglycemic clamp (gold
      standard for measuring insulin sensitivity) in insulin-resistant obese subjects.

      Secondary objectives are to:

        -  Test whether supplementation PP improves insulin sensitivity to tissue (fat and muscle)
           and compare the response to supplementation in these two tissues.

        -  Determining the cellular and molecular mechanisms involved in improving IR: regulation
           of inflammation, oxidative stress.

        -  Determine whether supplementation PP optimizes weight reduction compared to a standard
           single support.

      NSN: The number of subjects required was evaluated from our previous work (2013 Hokayem et
      al.) Whose main objective was to assess the impact of PD versus placebo in first degree
      relatives of patients with diabetes type 2. Under a bilateral alternative hypothesis of a
      nonparametric test (Mann-Whitney), 1: 1 ratio, a power of 80% and an alpha risk of 0.05, the
      number of subjects was estimated at 15 per group.

      Methodology: Anthropometric measurements, assessment of body composition (DEXA) system
      application characterization (metabolism, inflammation, oxidative stress, adipokines and
      insulin sensitivity: clamp hyperinsulinemic-euglycemic, lipopolysaccharides: LPS) / tissue
      characterization (biopsies of skeletal muscle and tissue adipose): insulin sensitivity,
      inflammation, oxidative stress, gene regulation (sirt1), mitochondrial activity / cell
      characterization (adipocyte precursor and muscle) insulin sensitivity, inflammation,
      oxidative stress, sirt1.

      Investigators hope to demonstrate that a non-pharmacological treatment based on nutritional
      doses of PP supplementation can improve insulin sensitivity in insulin-resistant obese
      patients, refer to optimize weight loss compared to a standardized management of obesity and
      determine the mechanisms involved.
    


Intervention name(s): Supplementation with red grapes polyphenol
Intervention type(s): Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Obesity; insulinoresistant; menopausal women; polyphenol