Diabetes leads to premature organ and system failure and considerably short
ens lifespan. Careful control of glucose levels may not be enough to preven
t the onset of complications in most diabetics. Compared with non-diabetics
, diabetic tissues must not only resist a much greater long-term threat fro
m hyperglycaemia-mediated reactive species but also defend themselves with
compromised antioxidant systems. Although antioxidant therapy is a logical
step in the prevention of oxidant and carbonyl stresses in the face of inte
rmittent hyperglycaemia, this approach is not yet universally accepted to b
e effective in preventing complications. Although there are many biochemica
l indices of oxidant stress, piecemeal elevations of individual markers may
not necessarily reflect true diabetic cellular antioxidant status. A dynam
ic process such as in vitro methaemoglobin generation may provide an opport
unity to compare the response of a diabetic erythrocyte with that of a non-
diabetic before and after corrective antioxidant therapy. Due to compromise
d cellular antioxidant capacity, diabetic cells generate less methaemoglobi
n in the presence of aromatic amine hydroxylamines, 4-aminophenol and nitri
te compared with non-diabetics. Agents such as dihydrolipoic acid have been
shown to correct methaemoglobin formation-mediated thiol deficits during i
n vitro studies. It is hoped that the progress of antioxidant supplementati
on studies in diabetics can be monitored with the aid of in vitro methaemog
lobin generation using agents such as hydroxylamines, 4-aminophenol and nit
rite. The most appropriate antioxidants and dosages can thus be recommended
to diabetics worldwide to attenuate the development of complications. (C)
2001 Elsevier Science B.V. All rights reserved.