Dicarboxylic acids as markers of fatty acid peroxidation in diabetes

Increased urinary excretion of dicarboxylic acids (DAs) has been well known in patients with diabetic ketoacidosis (DKA). It was known that small amounts of such DAs were also detected in urine from healthy humans. Upon chemical, radiation-induced or enzymatic oxidation, cis-polyunsaturated fatty acids (PUFA) have previously been shown to generate saturated short- and medium-chain length DAs. In diabetes, it was confirmed that the imbalance between the generation of free radicals and antioxidant defense systems increases oxidative stress and leads to the damage of lipid, which contains PUFA. Some peroxidation products of PUFA, such as malondialdehyde and conjugated diene, are generally known to be elevated in patients with diabetes. The present study was undertaken to determine if urinary excretion of DAs is elevated in diabetic patients without DKA. Urine samples from ten non-ketoacidotic patients with type 2 diabetes and ten healthy subjects were examined for DAs by combined gas chromatography and mass spectrometry with selected ion monitoring. The diabetic subjects had significantly (P<0.001) more increased DAs excretion in urine than corresponding healthy subjects. The yields of DAs in each group decreased in the order adipic>suberic>sebacic acid. Being stable and easily detectable compounds, DAs may be considered potential markers of oxidative attack on PUFA in diabetes.