Evidence map›Paper›PMID 40715470›Full record

ArticleCommunications medicine2025

Altered branched chain ketoacids underlie shared metabolic phenotypes in type 1 diabetes and maple syrup urine disease.

Domenico Roberti, Abby L Grier, Julie A Reisz, Fara Vallefuoco, Alicia Key, Shaun Bevers, Monika Dzieciatkowska, Travis Nemkov, Marcella Contieri, Angela Zanfardino and 8 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. 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 · 2026
    Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Domenico Roberti *Department of Woman, Child and General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy. domenico.roberti@unicampania.it.ORCID http://orcid.org/0000-0003-0948-3910
Abby L Grier *Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-5199-8670
Julie A ReiszDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-7296-4963
Fara VallefuocoDepartment of Woman, Child and General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
Alicia KeyDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-8787-8144
Shaun BeversDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-2000-6106
Monika DzieciatkowskaDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-9947-2520
Travis NemkovDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Marcella ContieriDepartment of Woman, Child and General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
Angela ZanfardinoDepartment of Woman, Child and General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
Philip J NorrisVitalant Research Institute, San Francisco, CA, USA.
Michael P BuschVitalant Research Institute, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1446-125X
Vienna KauffmanCentral Pennsylvania Clinic, Belleville, PA, USA.
Holmes D MortonCentral Pennsylvania Clinic, Belleville, PA, USA.
Eric J EarleyRTI International, Research Triangle Park, NC, USA.
Grier P PageRTI International, Research Triangle Park, NC, USA.
Pierluigi MarzuilloDepartment of Woman, Child and General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.ORCID http://orcid.org/0000-0003-4682-0170
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. angelo.dalessandro@cuanschutz.edu.ORCID http://orcid.org/0000-0002-2258-6490

Funding

The Impact of Oxidative Stress on Erythocyte BiologyR01HL148151 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI D'ALESSANDRO, ANGELO, KARAFIN, MATTHEW S · 2019 to 2022
$8.9M
The role of ferroptosis in red cell aging in vivo and in vitroR01HL146442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Angelo D'Alessandro, Adam N. Goldfarb · 2019 to 2026
$5.4M
The paradoxical response to iron in pulmonary hypertension of sickle cell diseaseR01HL161004 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BUEHLER, PAUL WERNER, D'ALESSANDRO, ANGELO · 2022 to 2025
$2.7M
Interactions between the ADORA2b/Sphk1axis and the AE1-Hb switch in red blood cell aging in vivo and in vitroR01HL149714 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI D'ALESSANDRO, ANGELO · 2020 to 2023
$2.6M
MIRAGES: Metabolic Investigation of Red blood cells as a function of Aging, Genetics, Environment, and StorageR21HL150032 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI D'ALESSANDRO, ANGELO · 2020 to 2021
$414k
NHLBI NIH HHS R01 HL146442NHLBI NIH HHS R01 HL161004U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL146442U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL148151U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL149714U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R21HL150032
6 · The paper itself

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.

Identifiers

PMID40715470
PMCPMC12297452

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.