Oxidative stress plays a key role in the development of chronic
diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and
insulin resistance with
branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic changes associated with increased oxidative stress, as assessed by
nitrotyrosine levels, in
type 2 diabetes (T2DM). Serum samples of 80 patients with
insulin-treated T2DM are analyzed by AA-targeted metabolomics using ultrahigh-performance liquid chromatography/mass spectrometry. Patients are divided into two groups based on their
nitrotyrosine levels: the highest level of oxidative stress (Q4
nitrotyrosine) and lower levels (Q1-Q3 nitrotyrosine). The identification of
biomarkers is performed in MetaboAnalyst version 5.0 using a t-test corrected for false discovery rate, unsupervised principal component analysis and supervised partial least-squares discriminant analysis (PLS-DA). Four AAs have significantly different levels between the groups for highest and lower oxidative stress.
Cysteine,
phenylalanine and
tyrosine are substantially increased while
citrulline is decreased (p-value <0.05 and variable importance in the projection [VIP] >1). Corresponding pathways that might be disrupted in patients with high oxidative stress are
phenylalanine,
tyrosine and
tryptophan biosynthesis,
arginine biosynthesis,
phenylalanine metabolism,
cysteine and
methionine metabolism and
tyrosine metabolism.