title: Urinary conjugated α-tocopheronolactone--a biomarker of oxidative stress in children with type 1 diabetes.
abstract: Increased oxidative stress has been implicated in both the onset and the progression of diabetes mellitus and its complications. The development of easy to measure biomarkers of oxidative stress would, therefore, help in determining in a prospective manner the impact of glycemic control on oxidative stress and macrovascular disease in patients with diabetes. We report the development and validation of a novel method to directly measure the urinary concentrations of the conjugated metabolites of vitamin E (α-tocopherol) and investigate whether the oxidized metabolite α-tocopheronolactone (α-TL) could be used as a biomarker of oxidative stress in children with type 1 diabetes. A novel method using liquid chromatography-tandem mass spectrometry was developed and used to measure directly and rapidly the urinary concentrations of the glucuronidated and sulfated metabolites of α-tocopherol in 32 young patients with type 1 diabetes and age-matched controls. The mean concentrations of the glucuronidated and sulfated conjugates of α-TL were all highly significantly increased in the children with type 1 diabetes (p<0.001). The results suggest that the measurement of the urinary concentrations of α-TL conjugates may provide a useful biomarker of oxidative stress in diabetes and possibly in other clinical conditions in which oxidative stress has been implicated.
authors.affiliation: Biochemistry Research Group, Clinical & Molecular Genetics Unit, University College London Institute of Child Health, London WC1N 1EH, UK.
authors.forename: Gayatri
authors.initials: G
authors.lastname: Sharma
authors.forename: David P
authors.initials: DP
authors.lastname: Muller
authors.forename: Stephen M
authors.initials: SM
authors.lastname: O'Riordan
authors.forename: Sinead
authors.initials: S
authors.lastname: Bryan
authors.forename: Mehul T
authors.initials: MT
authors.lastname: Dattani
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hindmarsh
authors.forename: Kevin
authors.initials: K
authors.lastname: Mills
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D002648:Child; D002853:Chromatography, Liquid / Q000379:methods*; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D015394:Molecular Structure; D018384:Oxidative Stress; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000652:urine
chemical_list: D015415:Biomarkers; D014810:Vitamin E; C034599:tocopheronolactone