Clinical Trial 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.
