Lipidome characterisation and sex-specific differences in type 1 and type 2 diabetes mellitus
Barranco-Altirriba, Maria (Institut de Recerca Sant Joan de Déu)
Alonso Pedrol, Núria (Universitat Autònoma de Barcelona. Departament de Medicina)
Weber, Ralf J.M. (University of Birmingham)
Lloyd, Gavin R. (University of Birmingham)
Hernandez, Marta (Institut de Recerca Biomèdica)
Yanes, Oscar (Universitat Rovira i Virgili)
Capellades, Jordi (Institut d'Investigació Sanitària Pere Virgili)
Jankevics, Andris (Netherlands Proteomics Center)
Winder, Catherine (University of Liverpool)
Falguera, Mireia (Universitat de Lleida)
Franch-Nadal, Josep (Institut Universitari d'Investigació en Atenció Primària Jordi Gol)
Dunn, Warwick B. (University of Liverpool)
Perera Lluna, Alexandre (Institut de Recerca Sant Joan de Déu)
Castelblanco, Esmeralda (Institut Universitari d'Investigació en Atenció Primària Jordi Gol i Gurina)
Mauricio Puente, Dídac (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Background: In this study, we evaluated the lipidome alterations caused by type 1 diabetes (T1D) and type 2 diabetes (T2D), by determining lipids significantly associated with diabetes overall and in both sexes, and lipids associated with the glycaemic state. Methods: An untargeted lipidomic analysis was performed to measure the lipid profiles of 360 subjects (91 T1D, 91 T2D, 74 with prediabetes and 104 controls (CT)) without cardiovascular and/or chronic kidney disease. Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) was conducted in two ion modes (positive and negative). We used multiple linear regression models to (1) assess the association between each lipid feature and each condition, (2) determine sex-specific differences related to diabetes, and (3) identify lipids associated with the glycaemic state by considering the prediabetes stage. The models were adjusted by sex, age, hypertension, dyslipidaemia, body mass index, glucose, smoking, systolic blood pressure, triglycerides, HDL cholesterol, LDL cholesterol, alternate Mediterranean diet score (aMED) and estimated glomerular filtration rate (eGFR); diabetes duration and glycated haemoglobin (HbA1c) were also included in the comparison between T1D and T2D. Results: A total of 54 unique lipid subspecies from 15 unique lipid classes were annotated. Lysophosphatidylcholines (LPC) and ceramides (Cer) showed opposite effects in subjects with T1D and subjects with T2D, LPCs being mainly up-regulated in T1D and down-regulated in T2D, and Cer being up-regulated in T2D and down-regulated in T1D. Also, Phosphatidylcholines were clearly down-regulated in subjects with T1D. Regarding sex-specific differences, ceramides and phosphatidylcholines exhibited important diabetes-associated differences due to sex. Concerning the glycaemic state, we found a gradual increase of a panel of 1-deoxyceramides from normoglycemia to prediabetes to T2D. Conclusions: Our findings revealed an extensive disruption of lipid metabolism in both T1D and T2D. Additionally, we found sex-specific lipidome changes associated with diabetes, and lipids associated with the glycaemic state that can be linked to previously described molecular mechanisms in diabetes.
Ajuts:	Instituto de Salud Carlos III PI15/0625 Agencia Estatal de Investigación PID2021-122952OB-I00 European Commission PI18/0328 European Commission PI17/01362 Fundació la Marató de TV3 303/C/2016 Instituto de Salud Carlos III AC22/00035
Nota:	Altres ajuts: This research was supported by CIBER-Consorcio Centro de Investigación Biomèdica en Red-CIBERDEM (leading group CB15/00071) and Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Ministry of Science and Innovation; Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau is accredited by the Generalitat de Catalunya as Centre de Recerca de Catalunya (CERCA); B2SLab is certified as 2021 SGR 01052; We want to particularly acknowledge the participants, and the IGTP-HUGTP (B.0000643) and IRBLleida Biobank (B.0000682) integrated in the PLATAFORMA BIOBANCOS (PT20/00050 and PT20/00021, respectively); The authors are also thankful to the COST Action EpiLipidNET, CA19105 - Pan-European Network in Lipidomics and EpiLipidomics; The first author gratefully acknowledges the Universitat Politècnica de Catalunya and Banco Santander for the financial support of her predoctoral grant; We would like to thank Joana Rossell and Minerva Granado-Casas for her feedback during the revision process; The authors acknowledge Amanda Prowse (Lochside Medical Communications Ltd.) for support in editing the paper.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Sex-specific differences ; Type 1 diabetes ; Type 2 diabetes ; Untargeted lipidomics
Publicat a:	Cardiovascular diabetology, Vol. 23 Núm. 1 (december 2024) , p. 109, ISSN 1475-2840

DOI: 10.1186/s12933-024-02202-5
PMID: 38553758

13 p, 5.0 MB

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