Altered neopterin and IDO in kynurenine metabolism based on LC-MS/MS metabolomics study: Novel therapeutic checkpoints for type 2 diabetes mellitus.
Clin Chim Acta
; 557: 117859, 2024 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-38518968
ABSTRACT
BACKGROUND:
This study assessed the alternations of kynurenine pathway (KP) and neopterin in type 2 diabetes mellitus (T2DM) and explored possible differential metabolites.METHODS:
A fresh residual sera panel was collected from 80 healthy control (HC) individuals and 72 T2DM patients. Metabolites/ratios of interest including tryptophan (TRP), kynurenine (KYN), 5-hydroxytryptamine (5HT), kynurenic acid (KA), xanthurenic acid (XA), neopterin (NEO), KA/KYN ratio and KYN/TRP ratio were determined using a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics approach, and the difference between groups was assessed. Supervised orthogonal partial least squares-discriminant analysis and differential metabolite screening with fold change (FC) were performed to identify distinct biomarkers. The diagnostic performance of KP metabolites in T2DM was evaluated.RESULTS:
Significant decreases of TRP, 5HT, KA, XA, and KA/KYN and increases of KYN/TRP and NEO in T2DM compared to HC group were observed (P < 0.05). The KP metabolites panel significantly changed between T2DM and HC groups (Q2 0.925, P < 0.005). 5HT (FC 0.63, P < 0.01) and NEO (FC 3.27, P < 0.01) were proven to be distinct differential metabolites. A combined testing of fasting plasma glucose and KYN/TRP showed good value in the prediction of T2DM (AUC 0.904, 95% CI 0.843-0.947).CONCLUSIONS:
The targeted LC-MS/MS metabolomics study is a powerful tool for evaluating the status of T2DM. This study facilitated the application of KP metabolomics into future clinical practice. 5HT and NEO are promising biomarkers in T2DM. KYN/TRP was highly associated with the development of T2DM and may serve as a potential treatment target.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Quinurenina
Límite:
Humans
Idioma:
En
Revista:
Clin Chim Acta
Año:
2024
Tipo del documento:
Article