Objective: Sustained hyperglycemia is associated with low cellular levels of the antioxidant glutathione (GSH), which leads to tissue damage due to oxidative stress. We tested the hypothesis that diminished GSH in adult patients with uncontrolled type 2 diabetes is due to decreased synthesis, and measured the effect of dietary supplementation with its precursors cysteine and glycine on GSH synthesis rate and oxidative stress.
Research design and methods: We infused 12 diabetic patients and 12 non-diabetic controls with [2H2]-glycine to measure GSH synthesis, and also measured intracellular GSH concentrations, reactive oxygen metabolites, and lipid peroxides. Diabetic patients were re-studied after two weeks of dietary supplementation with the GSH precursors cysteine and glycine.
Results: Compared to controls, diabetic subjects had significantly higher fasting glucose (5.0±0.1 vs. 10.7±0.5 mmol/L, p<0.001), lower erythrocyte concentrations of glycine (514.7±33.1 vs. 403.2±18.2, μmol/L, P<0.01) and cysteine (25.2±1.5 vs. 17.8±1.5, μmol/L, P<0.01), lower GSH concentrations (6.75±0.47 vs. 1.65±0.16 μmol/g.Hb, p<0.001), diminished fractional (79.21±5.75 vs. 44.86±2.87 %/d, p<0.001) and absolute (5.26±0.61 vs. 0.74±0.10 μmol/g.Hb/d, p<0.001) GSH synthesis rates, and higher reactive oxygen metabolites (286±10 vs. 403±11 U.Carr, p<0.001), and lipid peroxides (2.6±0.4 vs. 10.8±1.2 pg/ml, p<0.001). Following dietary supplementation in diabetic subjects, GSH synthesis and concentrations increased significantly, and plasma oxidative stress and lipid peroxides decreased significantly.
Conclusions: Patients with uncontrolled type 2 diabetes have severely deficient synthesis of glutathione due to limited precursor availability. Dietary supplementation with GSH precursor amino-acids can restore GSH synthesis and lower oxidative stress and oxidant damage in the face of persistent hyperglycemia.
- Received May 26, 2010.
- Accepted September 30, 2010.
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