ArticleCommunications medicine2025
Altered branched chain ketoacids underlie shared metabolic phenotypes in type 1 diabetes and maple syrup urine disease.
Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Performance of nine large language models on real-world polysomnography interpretation for obstructive sleep apnea: a multi-dimensional comparative analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Activation of a branched-chain amino acid rheostat restores replication-dependent hematopoietic stem cell fitness.Cell stem cell · 2026Article
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Authors and funding
18 authors.
Funding
Abstract
backgroundDiabetic ketoacidosis is an acute, potentially life-threatening, metabolic complication and often first presentation of type 1 diabetes (T1D) mellitus. Here, we investigated the metabolic and lipid profiles from pediatric patients with T1D, at initial diagnosis and after two weeks of insulin treatment, employing findings from patients affected by maple syrup urine disease (MSUD) and the Recipient Epidemiology and Donor Evaluation Study (REDS) III RBC Omics.
methods27 patients with newly onset T1D were assessed at the University of Campania "L. Vanvitelli" at first diagnosis and 2 weeks after therapy with insulin. As part of the REDS-III RBC Omics, whole blood was collected from 13,091 healthy blood donors. Whole blood was also collected from 3 patients with MSUD by biallelic inactivating mutation of BCKDHA. Metabolomics and Lipidomics were performed via UHPLC-MS/MS.
resultsOur findings highlight a newly identified associations among short-chain hydroxyacyl-carnitines, ketoacidosis, and hematological alterations in T1D. An associative linkage with SNPs in the regions coding for branched chain ketoacid dehydrogenase A and B (BCDHKA/B) is noted by leveraging measurements of the same metabolites in over 13,000 healthy genetically characterized donor volunteers. MSUD, a rare genetic disorder characterized by inactivating mutations of the BCDHKA gene leading to inability to metabolize branched-chain amino acids, manifests a strong association between the branched-chain amino acid-derived ketoacids, associated acyl-carnitines, and acidosis.
conclusionsThese results indicate that T1D hematological alterations at onset might act as biomarkers linked to circulating levels of short-chain acyl-carnitines, providing risk stratification for T1D and potentially for MSUD. Carnitine metabolism may be a promising therapeutic target for both diseases.
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