Acute changes in blood glucose do not alter blood glutathione synthesis in adolescents with poorly controlled type 1 diabetes mellitus

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 A1c, 9.2% ± 0.5%) received two 5-hour intravenous infusions of L-[3,3-2H2]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 2H2-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.