Glutathione in overweight patients with poorly controlled type 2 diabetes

Abstract

Increased lipid peroxidation due to an altered intracellular ratio between free radicals and antioxidant systems has been associated with development of diabetic complications. This report explores the biochemical reliability of this hypothesis by measuring glutathione (GSH) in overweight patients with poorly controlled type 2 diabetes. GSH, a crucial antioxidant and cofactor for the selenium-dependent glutathione peroxidase (GSHPx), was analyzed in red blood cells. Ten overweight and poorly controlled type 2 diabetic patients (6 women and 4 men, age 45 –60 years, body mass index (BMI) 26 –32 kg/m2, HbA1c > 9.4%) and 13 healthy normal weight controls (7 women and 6 men, age 40–60 years, BMI 20–25 kg/m2, HbA1c <6.0 %) were included in the study. The intracellular level of GSH in red blood cells (mean 1.54 mmol/l) of the diabetic patients was reduced to 60% of reference values (mean 2–6 mmol/l). Reduced activity of GSHPx and increased levels of peroxides in diabetic patients have been found previously. Discussed are several mechanisms that contribute to the depletion of GSH in poorly controlled type 2 diabetic patients, involving reduced levels of NADPH that is essential for the regeneration of GSH in vivo. The probability of direct trapping of GSH to sugar aldehydes that invade the intracellular space in diabetic states should also be taken into account. Therapeutic trials with antioxidants that can regenerate the intracellular level of GSH are scarce but promising. An attractive hypothesis is that intracellular excesses of glucose inhibit the antioxidant systems primarily by its ability to cause depletion of the crucial protector GSH. The ultimate effects of such derangement of the protective systems against free radicals may involve vascular and neurological complications. J. Trace Elem. Exp. Med. 13:105–111, 2000. © 2000 Wiley-Liss, Inc.