title: Endothelial function, insulin action and cardiovascular risk factors in young healthy adult offspring of parents with Type 2 diabetes: effect of vitamin E in a randomized double-blind, controlled clinical trial.
abstract: OBJECTIVE
  Endothelial dysfunction, insulin resistance and oxidative stress are believed to be central and associated mechanisms in atherogenesis. We aimed to determine the effect of the antioxidant vitamin E on endothelial function, insulin action and cardiovascular risk markers in young healthy adult offspring of parents with Type 2 diabetes.
  
  
  METHODS
  Healthy, glucose-tolerant adults (18-38 years), 14 (12 male/2 female) with at least one parent with Type 2 diabetes, and 14 (12 male/2 female) subjects with no family history of diabetes (controls) were studied. Insulin action was assessed by euglycaemic hyperinsulinaemic clamp (1 mU/kg/min). Endothelial function was assessed by forearm blood flow (FBF) responses to intra-brachial artery infusions of acetylcholine (ACh) (endothelium-dependent vasodilation), sodium nitroprusside (SNP) (endothelium-independent vasodilation) and N(G)-monomethyl L-arginine (LNMMA) (nitric oxide synthase inhibition). Thirteen offspring (18-38 years, 11 male/2 female, BMI < 30 kg/m2) completed a randomized, double-blind, crossover trial (12 weeks vitamin E 800 IU/day or placebo, 6-week washout).
  
  
  RESULTS
  Exogenous glucose infusion rates to maintain euglycaemia were positively associated with response to acetylcholine in offspring (r = 0.61, P < 0.05), and were linked with triglycerides. Vitamin E had no effect on endothelial function, insulin action or cardiovascular risk markers in healthy adult offspring of parents with Type 2 diabetes.
  
  
  CONCLUSIONS
  Our results support a positive association between insulin action and endothelial-dependent vasodilation in young healthy adult offspring of parents with Type 2 diabetes, but indicate no effect of vitamin E on these parameters.
authors.affiliation: Regional Centre for Endocrinology & Diabetes, Royal Victoria Hospital, Belfast, N. Ireland, UK.
authors.forename: P T
authors.initials: PT
authors.lastname: McSorley
authors.forename: P M
authors.initials: PM
authors.lastname: Bell
authors.forename: I S
authors.initials: IS
authors.lastname: Young
authors.forename: A B
authors.initials: AB
authors.lastname: Atkinson
authors.forename: B
authors.initials: B
authors.lastname: Sheridan
authors.forename: J P H
authors.initials: JP
authors.lastname: Fee
authors.forename: D R
authors.initials: DR
authors.lastname: McCance
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000235:genetics; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010375:Pedigree; D012307:Risk Factors; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D007328:Insulin; D014810:Vitamin E; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester