Targeted metabolomics analysis of amino acids and acylcarnitines as risk markers for diabetes by LC–MS/MS technique

Abstract

Diabetes is a common chronic disease affecting millions of people worldwide. It underlies various complications and imposes many costs on individuals and society. Discovering early diagnostic biomarkers takes excellent insight into preventive plans and the best use of interventions. Therefore, in the present study, we aimed to evaluate the association between the level of amino acids and acylcarnitines and diabetes to develop diabetes predictive models. Using the targeted LC–MS/MS technique, we analyzed fasting plasma samples of 206 cases and 206 controls that were matched by age, sex, and BMI. The association between metabolites and diabetes was evaluated using univariate and multivariate regression analysis with adjustment for systolic and diastolic blood pressure and lipid profile. To deal with multiple comparisons, factor analysis was used. Participants' average age and BMI were 61.6 years, 28.9 kg/m2, and 55% were female. After adjustment, Factor 3 (tyrosine, valine, leucine, methionine, tryptophan, phenylalanine), 5 (C3DC, C5, C5OH, C5:1), 6 (C14OH, C16OH, C18OH, C18:1OH), 8 (C2, C4OH, C8:1), 10 (alanine, proline) and 11 (glutamic acid, C18:2OH) were positively associated with diabetes. Inline, factor 9 (C4DC, serine, glycine, threonine) and 12 (citrulline, ornithine) showed a reverse trend. Some amino acids and acylcarnitines were found as potential risk markers for diabetes incidents that reflected the disturbances in the several metabolic pathways among the diabetic population and could be targeted to prevent, diagnose, and treat diabetes.

The association between acylcarnitine and amino acids profile and metabolic syndrome and its components in Iranian adults: Data from STEPs 2016

“…As for amino acids, nearly all amino acids were significantly higher in men in comparison to those in women in both groups. These findings were in line with several studies conducted on other metabolic disorders (21,46,47). Specifically, it has been suggested that amino acids especially BCAA may be regulated differently by sex.…”

“…They showed that Leu, Val, and Phe were positively associated with the concentration of TG and 2-h postprandial glucose (29). Several cross-sectional and prospective cohort studies also point toward the strong association between plasma levels of BCAA and aromatic amino acids and central obesity, T2D, and insulin resistance (11,18,(37)(38)(39). Pearson's correlation coefficients were calculated for the 12 amino acids and 7 acylcarnitines with metabolic-related variables.…”

An integrated multi-omic approach demonstrates distinct molecular signatures between human obesity with and without metabolic complications: a case–control study

“…In addition to insulin resistance, amino acid catabolism is accelerated in diabetes reflected by muscle wasting along with increased uptake of alanine by the liver for gluconeogenesis and the breakdown of branched chain amino acids in muscle [ 54 , 55 ]. An increasing body of evidence has linked visceral adiposity, insulin resistance, and diabetes to plasma amino acid levels [ 56 ]. Yamaguchi et al have reported on the usefulness of measuring the plasma free amino acid profiles in evaluating risk for the metabolic syndrome, diabetes, dyslipidemia, and hypertension in a large cohort [ 57 ].…”

Metabolic signatures of insulin resistance in non-diabetic individuals

“…Plasma concentration of amino acids and acylcarnitines were quantified by a targeted metabolomics analysis using flow‐injection tandem mass spectrometry (triple quadrupole API 3200 SCIEX with electrospray ionization) accompanied by Thermo Scientific Dionex UltiMate 3000 standard HPLC system. The analysis method, including preparation, derivatization, and validation, is published elsewhere [ 31 , 32 ]. Briefly, 10 µL of samples/ calibrators/ quality control material were mixed with internal standard, and after centrifuging at 4˚C, supernatant fluids were separated and dried by a flow of nitrogen (99.9%) at 45˚C.…”