Altered amino acid metabolism between coronary heart disease patients with and without type 2 diabetes by quantitative 1H NMR based metabolomics

Abstract

Coronary heart disease (CHD) is a multifactorial disease associated with complicated altered metabolic pathways, especially when it occurs with type 2 diabetes (T2D). Identification of metabolic changes could provide further understanding of the underlying pathological link between with CHD and T2D. In this study, 61 controls, 30 consecutive patients with only T2D, 188 with confirmed CHD among which 50 also having T2D were enrolled. Quantitative 1H nuclear magnetic resonance (1H NMR) based metabonomic approach was used to obtain the plasma metabolic profiles of the study samples. Multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to evaluate the differences of metabolites. Compared with controls, there were significant differences in CHD patient with T2D groups including BCAAs (isoleucine, leucine, and valine) and phenylalanine by using quantitative metabolomic profiling (all p < 0.05). With OPLS-DA, the results showed that, compared to CHD patients without T2D, there had higher levels of metabolites for leucine, valine, fumarate, tyrosine, and phenylalanine in the plasma of CHD patients with T2D. Moreover, the CHD patients with T2D showed modified phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis and degradation compared with CHD patients without T2D. By 1H NMR based quantitative metabolomic method, our findings suggest that T2D has important effects on BCAAs and AAAs metabolism in CHD patients indicating altered cardiac energy metabolism and activated signaling pathway could be potential targets for therapy in CHD disease combined with T2D.