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 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.
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Article info
Publication history
Published online: September 26, 2011
Accepted:
July 26,
2011
Received:
June 24,
2011
Footnotes
These results were presented, in part, in an abstract form at the meeting of the Pediatric Academic Societies, Baltimore, MD, May 2009 (abstract 3855-62).
Author contributions: DD and NM: designed the study, conducted the studies, overall supervision of studies, analyzed data, and wrote the manuscript; SW and SSm: coordinated and conducted the studies, gathered data, and participated in data analysis; SSw: analyzed samples and participated in data analysis. DD had primary responsibility for final content. All authors read and approved the final manuscript.
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Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
