Precise Metabolomics Defines Systemic Metabolic Dysregulation Distinct to Acute Myocardial Infarction Associated With Diabetes

Abstract

Background: Acute myocardial infarction (AMI) is a leading cause of death and disability. Diabetes is an important risk factor and a common comorbidity in AMI patients. The higher mortality risk of diabetes-AMI relative to nondiabetes-AMI indicates a need for specific treatment to improve clinical outcome. However, the global metabolic dysregulation of AMI complicated with diabetes is still unclear. We aim to systematically interrogate changes in the metabolic microenvironment immediate to AMI episodes in the absence or presence of diabetes. Methods: In this work, quantitative metabolomics was used to investigate plasma metabolic differences between diabetes-AMI (n=59) and nondiabetes-AMI (n=59) patients. A diverse array of perturbed metabolic pathways involving carbohydrate metabolism, lipid metabolism, glycolysis, tricarboxylic acid cycle, and amino acid metabolism emerged. Results: In all, our omics-oriented approach defined a metabolic signature of afflicted mitochondrial function aggravated by concurrent diabetes in AMI patients. In particular, our analyses uncovered N-lactoyl-phenylalanine and lysophosphatidylcholines as key functional metabolites that skewed the metabolic picture of diabetes-AMI relative to nondiabetes-AMI. N-lactoyl-phenylalanine was strongly associated with metabolic indicators reflective of mitochondrial overload and negatively correlated with HbA1c specifically in hyperglycemic AMI, suggestive of its central role in glucose utilization and mitochondrial energy production instrumental to the clinical outcome of diabetes-AMI. Reductions in lysophosphatidylcholines, which were negatively correlated with blood glucose and inflammatory markers, might further compromise glucose expenditure and aggravate inflammation leading to poorer prognosis in diabetes-AMI. Conclusions: As circulating metabolite levels are amenable to therapeutic intervention, such shifts in metabolic signatures provide new clues and potential therapeutic targets specific to the treatment of diabetes-AMI.

Non-invasive monitoring and classification of coronary heart disease by metabolomics and lipidomics

“…6A-B, AMI and NCHD_MAX0 have better classi cation when complicated with diabetes. Xia et al also found that the glucose utilization related metabolites, lysoPC and N-lactoyl-phenylalanin, skewed the metabolic pattern of AMI-diabetes relative to AMI-nondiabetes [32] . This information indicate that the molecular microenvironment of AMI-diabetes contributes to compromised cardiac function and worse outcomes [50,51] .…”

“…Diabetes mellitus (DM) is a well-known risk factor and a common comorbidity in cardiovascular disease patients [30,31] . Xia et al found that the worse outcome of diabetes-AMI verse nondebates-AMI was primarily induced by elevated blood glucose [32] . To further explore the cross regulation of coronary heart disease and diabetes, we divided CHD group into two subgroups according to the comorbidity, namely, DM-CHD and non-diabetes (NDM)-CHD, as well as the NCHD group for the same operation (Suppl.…”

Inflammation and Insulin Resistance-Derived Indicator Predicts Adverse Cardiovascular Outcomes in Heart Failure Patients Undergoing Percutaneous Coronary Intervention

“…CTI is mainly determined by two critical components, the one is in ammation represented by the CRP, the other one is IR represented by the TyG index. In ammation and IR are both important components of residual cardiovascular risk factors and confer an enhanced risk of AMI heart failure [24][25][26][27]. The prevalence of diabetes has increased by more than tenfold since the 1980s in China owing to the ageing populations and improving socioeconomic status [2].…”

Glutamine supplementation alleviated aortic atherosclerosis in mice model and in vitro

“…Mice were treated for 18 weeks followed by analysis of aortic tissue untargeted metabolites. A total of 1330 identified metabolites were characterized and precisely quantitated using isotope-labeled internal standards, which included organic acids and derivatives (382); lipids and lipid-like molecules (345); undefined metabolites (196); organoheterocyclic compounds (117); organic oxygen compounds (98); benzenoids (89); nucleosides, nucleotides, and analogs (37); organic nitrogen compounds (35); phenylpropanoids and polyketides (25); alkaloids and derivatives (5); and lignans, neolignans and related compounds (1). PCA showed that the QC samples clustered together and their metabolome profiles were correlated indicating the stability and reproducibility of our metabolome data (Figure S1).…”

“…Atherosclerosis is a chronic inflammatory disease. Our team's recent clinical serum metabonomic detection showed that compared with that in nondiabetic acute myocardial infarction, the expression of glutamine in diabetic acute myocardial infarction is significantly reduced [1], suggesting that glutamine is significantly consumed. Previous studies have shown that glutamine improves fasting plasma glucose levels [2] and has anti‐inflammatory effects [3, 4].…”