title: Evidence for accelerated rates of glutathione utilization and glutathione depletion in adolescents with poorly controlled type 1 diabetes.
abstract: Depletion of glutathione, an important antioxidant present in red cells, has been reported in type 1 diabetes, but the mechanism of this depletion has not been fully characterized. Glutathione depletion can occur through decreased synthesis, increased utilization, or a combination of both. To address this issue, 5-h infusions of l-[3,3-(2)H(2)]cysteine were performed in 16 diabetic adolescents divided into a well-controlled and a poorly controlled group and in eight healthy nondiabetic teenagers as control subjects (HbA(1c) 6.3 +/- 0.2, 10.5 +/- 0.6, and 4.8 +/- 0.1%, respectively). Glutathione fractional synthesis rate was determined from (2)H(2)-cysteine incorporation into blood glutathione. We observed that 1) erythrocyte cysteine concentration was 41% lower in poorly controlled patients compared with well-controlled patients (P = 0.009); 2) erythrocyte glutathione concentration was approximately 29% and approximately 36% lower in well-controlled and poorly controlled patients compared with healthy volunteers; and 3) the fractional synthesis rate of glutathione, although similar in well-controlled and healthy subjects (83 +/- 14 vs. 82 +/- 11% per day), was substantially higher in the poorly controlled group (141 +/- 23% per day, P = 0.038). These findings suggest that in diabetic adolescents, poor control is associated with a significant depletion of blood glutathione and cysteine, due to increased rates of glutathione utilization. This weakened antioxidant defense may play a role in the pathogenesis of diabetes complications.
authors.affiliation: Nemours Children's Clinic, Research Department, 5 North, 807 Children's Way, Jacksonville, FL 32207, USA. ddarmaun@chu-nantes.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Darmaun
authors.forename: Shiela D
authors.initials: SD
authors.lastname: Smith
authors.forename: Shawn
authors.initials: S
authors.lastname: Sweeten
authors.forename: Brenda K
authors.initials: BK
authors.lastname: Sager
authors.forename: Susan
authors.initials: S
authors.lastname: Welch
authors.forename: Nelly
authors.initials: N
authors.lastname: Mauras
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D049628:Body Size; D003545:Cysteine / Q000008:administration & dosage / Q000494:pharmacology*; D003903:Deuterium; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood* / Q000172:deficiency; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011865:Radioisotope Dilution Technique; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D003903:Deuterium; D005978:Glutathione; D003545:Cysteine