Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity


Dr P. Kar, Academic Unit of Diabetes and Endocrinology, Queen Alexandra Hospital, Portsmouth, PO6 3LY UK. E-mail: drparthakar@googlemail.com


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.