ARS | Publication request: OXIDATIVE STRESS AND GLUTATHIONE SYNTHESIS IN TYPE 2 DIABETES: A STABLE ISOTOPE APPROACH

Submitted to: Diabetes
Publication Type: Abstract Only
Publication Acceptance Date: February 1, 2002
Publication Date: February 1, 2002
Citation: McKay, S., Morlese, J., Jackson, A., Forrester, T., Balasubramanyam, A., Reeds, P., Jahoor, F. 2002. Oxidative stress and glutathione synthesis in type 2 diabetes: a stable isotope approach. Diabetes. 51:A317.

Technical Abstract: Many of the complications of diabetes are linked to oxidative damage. We set out to determine whether the reduced antioxidant capacity (as reflected by glutathione concentration) in type 2 diabetes is due to reduced synthesis or increased consumption of glutathione (GSH), and whether short-term dietary supplementation with glycine and cysteine, precursors of GSH, would improve oxidant status. 2H2-glycine was infused for 7 hours to measure glycine kinetics and red blood cell GSH (RBC-GSH) synthesis in diabetic and euglycemic subjects. These same measurements were repeated in a subset of diabetic subjects after 2 weeks of supplementation with glycine and cysteine, the precursors of glutathione. Lipid hydroperoxide and lymphocyte glutathione concentration were also measured. Twenty euglycemic subjects and 10 subjects with type 2 diabetes participated in the unsupplemented study. Three subjects with type 2 diabetes were studied 2 additional times: after 2 weeks of supplementation with glycine, and after 2 weeks of supplementation with cysteine (given in the form of N-acetylcysteine (NAC)). Compared to controls, diabetes subjects had a significantly higher lipid hydroperoxide concentration (11.4±1.5 vs 6.5±0.5 µmol/L, p<0.05), and lower fractional (38±5 vs 62±4%/day) and absolute (5.0±0.4 vs 8.8±1.1 µmol/gHb/day) synthesis rates of RBC-GSH indicative of increased oxidative stress. With cysteine supplementation, the diabetic subjects were able to double their fractional (38±5 vs 78±14%, p<0.05) and absolute (5.0±0.4 vs 8.8±1.1 µmol/gHb/day, p<0.05) synthesis rate of RBC-GSH. Diabetic subjects also had significantly lower cysteine flux (30±2 vs 40 ±4 µmol/kg/hr, p<0.05) and glycine flux (102±5 vs 160±14 µmol/kg/hr, p<0.05. We conclude that subjects with type 2 diabetes have decreased oxidant capacity, evidenced by reduced synthesis of glutathione, and they are under increased oxidative stress, evidenced by higher lipid hydroperoxide concentration; more importantly, supplementation with NAC stimulates glutathione synthesis, thereby improving antioxidant capacity and reducing oxidative stress. Long-term NAC supplementation may reduce oxidant induced complications of diabetes.