Objective: Current research has focused upon the potential links between novel markers of vascular risk such as endothelial dysfunction, oxidative stress, inflammation and insulin resistance in the pathogenesis of Type 2 diabetes and its complications. Grape seed extract (GSE), a flavonoid-rich product, is a potential moderator of these markers. This study aimed to test the hypothesis that GSE may improve these markers in high-risk cardiovascular subjects with Type 2 diabetes.

Research design and methods: Thirty-two Type 2 diabetes mellitus patients, prescribed diet or oral glucose-lowering agents, received GSE (600 mg/day) or placebo for 4 weeks in a double-blinded randomized crossover trial. Markers of endothelial function (measured by photoplethysmography), oxidative stress [total antioxidant status (TAOS), reduced glutathione (GSH)/oxidized glutathione (GSSG)], inflammation [highly sensitive C-reactive protein (hsCRP), urinary albumin : creatinine ratio), insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] and metabolism (fructosamine, lipid profile) was measured at baseline and after intervention with GSE or placebo.

Results: Baseline characteristics (16 male and 16 female): age 61.8 +/- 6.36 years; body mass index 30.2 +/- 5.92 kg/m2; diabetes duration 5.9 +/- 2.14 years. Following GSE (but not placebo), significant changes were noted in fructosamine (282 +/- 40.9 vs. 273 +/- 50.2 mmol/l; P = 0.0004); whole blood GSH (2359 +/- 823 vs. 3595 +/- 1051 mmol/l; P < 0.01) and hsCRP (3.2 +/- 3.65 vs. 2.0 +/- 2.2 mg/l; P = 0.0006). Total cholesterol concentration also decreased (4.5 +/- 0.96 vs. 4.3 +/- 0.99 mmol/l; P = 0.05). No statistically significant changes were shown in endothelial function, HOMA-IR or TAOS.

Conclusion: GSE significantly improved markers of inflammation and glycaemia and a sole marker of oxidative stress in obese Type 2 diabetic subjects at high risk of cardiovascular events over a 4-week period, which suggests it may have a therapeutic role in decreasing cardiovascular risk.