title: 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.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Academic Unit of Diabetes and Endocrinology, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK. drparthakar@googlemail.com
authors: P
authors: P
authors: Kar
authors: D
authors: D
authors: Laight
authors: H K
authors: HK
authors: Rooprai
authors: K M
authors: KM
authors: Shaw
authors: M
authors: M
authors: Cummings
mesh_terms: D000368:Aged; D000419:Albuminuria; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D019270:Fructosamine / Q000378:metabolism*; D056604:Grape Seed Extract / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D018384:Oxidative Stress / Q000187:drug effects*; D017156:Photoplethysmography; D010919:Placebos; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D056604:Grape Seed Extract; D010919:Placebos; D019270:Fructosamine; D002097:C-Reactive Protein