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Glutathione Articles - Diabetes
Glutathione in overweight
patients with poorly controlled type 2 diabetes
Jan Aaseth, Grethe Stoa-Birketvedt
J Trace Elem Exp Med. 13:105-111, 2000.
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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.
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