LC-MS-based conventional metabolomics combined with machine learning models to identify metabolic markers for the...

Changes in certain metabolites are linked to an increased risk of type I diabetes (T1D), making metabolite analysis a valuable tool for T1D diagnosis and treatment. This study aimed to identify a metabolic signature linked with T1D.

Untargeted metabolomic profiling was performed using liquid chromatography-mass spectrometry (LC-MS) on peripheral blood samples from T1D patients (n = 45) and healthy controls (n = 40). Data preprocessing and quality control were conducted using MetaboAnalyst 4.0. Differential metabolites (DMs) were identified via Wilcoxon rank-sum test (P< 0.05), and key diagnostic markers were selected using least absolute shrinkage and selection operator (LASSO) regression. A streptozotocin (STZ)-induced diabetic rat model was used for in vivo validation.

A total of 157 annotated metabolites were detected (58 in ESI- and 99 in ESI+ mode). Twenty-six DMs were identified, including 25 upregulated and 1 downregulated in the T1D group, mainly involving Acylcarnitines and xanthine metabolites. LASSO regression selected Hydroxyhexadecanoyl carnitine, Propionylcarnitine, and Valerylcarnitine as candidate markers. In the rat model, Hydroxyhexadecanoyl carnitine and Valerylcarnitine demonstrated strong diagnostic performance, with AUCs of 0.9383 (95% CI: 0.8786-0.9980) and 0.8395 (95% CI: 0.7451-0.9338), respectively (P< 0.01).

Hydroxyhexadecanoyl carnitine and Valerylcarnitine are closely linked to altered lipid oxidation in T1D and show strong potential as diagnostic biomarkers. These findings provide new insights into the metabolic basis of T1D and offer promising targets for early detection.