Diabetic patients exhibit an oxidative stress status, that is an imbalance between
reactive oxygen species and
antioxidant defences, in favour of the first ones. This oxidative stress, together with formation of
advanced glycation endproducts (AGEs), is involved in
diabetic complications. It could thus be of great interest to propose
antioxidant and/or anti-AGE
therapeutics as complementary treatment in these patients.
Antioxidants can be classical molecules such as
vitamin E,
lipoic acid or
N-acetylcysteine. Thus,
vitamin E supplementation can improve
insulin efficiency and glycemic equilibrium, as shown by the decrease of glycaemia, glycated haemoglobin and
fructosamine values. In addition, this kind of supplementation lowers plasma lipid peroxidation and oxidizability of
low density lipoproteins, which is involved in the
atherogenesis process. Moreover, it allows to fight against complications such as retinopathy. A second category is represented by molecules able to fight against the effects of glycation end-products (AGEs). They can act: either by preventing cellular action of AGEs; this is obtained with soluble receptors of
advanced glycation endproducts (sRAGE); or by inhibiting AGE formation (scavenging of reactive carbonyl intermediates). Nucleophilic compounds such as
pyridoxamine,
tenilsetam, 2,3-diaminophenazone,
OPB-9195 or
aminoguanidine can act in this way.
Aminoguanidine is able to limit the development of the main diabetes-associated complications in animals. A double-blind clinical assay has been conducted in type 2 diabetic patients in the United States and the Canada, in order to determine if
aminoguanidine is able to slow down the progression of diabetes-induced nephropathy. We will discuss about another guanidic molecule, i.e.
metformin, which is also able to scavenge AGEs, in the last part of this review. A third category of molecules is constituted by oral
antidiabetic molecules exhibiting
antioxidant properties. They are
thiazolidinediones (
troglitazone) and sulfonylureas (
gliclazide).
Troglitazone and
gliclazide can thus decrease
LDL oxidizability and monocyte adhesion to endothelial cells, which is an early step in the
atherogenesis process and which is stimulated by oxidised LDLs. Finally, a prospective way is devoted to oral
antidiabetic drugs exhibiting both
antioxidant and anti-AGE properties. A very used
antidiabetic drug of interest is
metformin (dimethylbiguanide), since it can prevent
diabetes complications not only by lowering glycaemia, but also by inhibiting AGE formation and by stimulating
antioxidant defences. The latter therapeutic approach constitutes a future way in the diabetes area, in order both to obtain a better
glycemic control and a least development of
diabetic complications.