Diet and nutrition play an essential role in the development and the clinical expression of
the most common health problems. Overeating and obesity induce oxidative stress, which has
been proposed to be a pathogenic mechanism leading to insulin resistance, type 2 diabetes
(T2D) and associated cardiovascular complications. The main objective of the proposed
research is to evaluate the beneficial effects of polyphenolic compounds derived from red
grape marc extracts on the cascade of events leading from overeating to oxidative stress and
insulin resistance. For that, we will study free radicals production, inflammatory markers,
adipokines, mitochondrial function, insulin sensitivity and energy substrate utilization in
healthy volunteers at risk for insulin resistance and T2D (1st degree relatives of T2D
patients with associated overweight). These volunteers will be randomized between a placebo
and a polyphenol group for 9 weeks. The demonstration of the beneficial effects of
polyphenols will be sensitized by high-fructose feeding for the last 6 days of the protocol.