title: Acute changes in blood glucose do not alter blood glutathione synthesis in adolescents with poorly controlled type 1 diabetes mellitus.
abstract: Depletion of blood glutathione (GSH), a key antioxidant, is associated with type 1 diabetes mellitus (T1D) and contributes to the pathophysiology of diabetes complications. The aim of the current study was to determine whether acute normalization of blood glucose would restore GSH kinetics in adolescents with poorly controlled T1D. Ten 16.9 ± 1.5-year-old (SE) adolescents who had had T1D for 8.5 ± 1.9 years and were free of complications but were in poor control (hemoglobin A(1c), 9.2% ± 0.5%) received two 5-hour intravenous infusions of L-[3,3-(2)H(2)]cysteine in the postabsorptive state on 2 separate days after blood glucose had been maintained overnight at 246 ± 24 mg/dL (hyperglycemia) or 118 ± 23 mg/dL (euglycemia) using intravenous insulin infusion. Blood GSH fractional synthesis rates were determined by mass spectrometry from (2)H(2)-cysteine incorporation into GSH. Neither blood GSH (551 ± 169 vs 541 ± 232 μmol/L, P = .629) nor GSH fractional synthesis rate (84% ± 30% vs 82% ± 33% d(-1), P = .965) was altered by the short-term change in glycemic control. This finding suggests that, in adolescents with poorly controlled T1D, either (a) blood glucose per se does not regulate GSH metabolism or (b) GSH may only respond to sustained, more chronic changes in blood glucose level.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Nemours Children's Clinic, Jacksonville, FL 32207, USA. ddarmaun@nemours.org
authors.forename: Dominique
authors.initials: D
authors.lastname: Darmaun
authors.forename: Susan
authors.initials: S
authors.lastname: Welch
authors.forename: Shiela
authors.initials: S
authors.lastname: Smith
authors.forename: Shawn
authors.initials: S
authors.lastname: Sweeten
authors.forename: Nelly
authors.initials: N
authors.lastname: Mauras
mesh_terms: D000293:Adolescent; D001774:Blood Chemical Analysis; D001786:Blood Glucose / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000008:administration & dosage / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000096:biosynthesis* / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D008297:Male
chemical_list: D001786:Blood Glucose; D003545:Cysteine; D005978:Glutathione; D006442:Glycated Hemoglobin