Lipidome characterisation and sex-specific differences in type 1 and type 2 diabetes mellitus

Maria Barranco-Altirriba; Núria Alonso; Ralf J.M. Weber; Gavin R. Lloyd; Marta Hernandez; Oscar Yanes; Jordi Capellades; Andris Jankevics; Catherine Winder; Mireia Falguera; Josep Franch-Nadal; Warwick B. Dunn; Alexandre Perera-Lluna; Esmeralda Castelblanco; Didac Mauricio

doi:10.1186/s12933-024-02202-5

Lipidome characterisation and sex-specific differences in type 1 and type 2 diabetes mellitus

Maria Barranco-Altirriba, Núria Alonso, Ralf J.M. Weber, Gavin R. Lloyd, Marta Hernandez, Oscar Yanes, Jordi Capellades, Andris Jankevics, Catherine Winder, Mireia Falguera, Josep Franch-Nadal, Warwick B. Dunn, Alexandre Perera-Lluna, Esmeralda Castelblanco^*, Didac Mauricio^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	109
Number of pages	13
Journal	Cardiovascular Diabetology
Volume	23
Issue number	1
DOIs	https://doi.org/10.1186/s12933-024-02202-5
Publication status	Published - 29 Mar 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Funding

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. This work was funded by Spanish Ministry of Health, Instituto de Salud Carlos III (Madrid, Spain) grants PI15/0625 (to DM and EC), PI17/01362 (to NA), PI18/0328 (to DM), FEDER “Una manera de hacer Europa”, and by Fundació La Marató de TV3 2016 (303/C/2016) (201602.30.31) (to NA). Spanish Ministry of Economy and Competitiveness, grant PID2021-122952OB-I00 funded by AEI 10.13039/501100011033 and by ERDF A way of making Europe, Instituto de Salud Carlos III (grant AC22/00035); and the CERCA Programme / Generalitat de Catalunya (to AP). 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.

Funders	Funder number
Banco Santander
Ministerio de Ciencia e Innovación
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina
Generalitat de Catalunya
Universitat Politècnica de Catalunya
Agencia Estatal de Investigación
Lochside Medical Communications Ltd.
Federación Española de Enfermedades Raras
Consejería de Salud y Familias, Junta de Andalucía
Fundació la Marató de TV3	303/C/2016, 201602.30.31
Instituto de Salud Carlos III	PI15/0625
CIBER-Consorcio Centro de Investigación Biomèdica en Red-CIBERDEM	CB15/00071
Ministerio de Economía y Competitividad	PID2021-122952OB-I00
European Commission	PI17/01362, PI18/0328
European Regional Development Fund	AC22/00035
IRBLleida Biobank	PT20/00050, PT20/00021, 0000682
European Cooperation in Science and Technology	CA19105

Keywords

Sex-specific differences
Type 1 diabetes
Type 2 diabetes
Untargeted lipidomics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12933-024-02202-5Licence: CC BY

s12933-024-02202-5Final published version, 5.04 MBLicence: CC BY

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Barranco-Altirriba, M., Alonso, N., Weber, R. J. M., Lloyd, G. R., Hernandez, M., Yanes, O., Capellades, J., Jankevics, A., Winder, C., Falguera, M., Franch-Nadal, J., Dunn, W. B., Perera-Lluna, A., Castelblanco, E., & Mauricio, D. (2024). Lipidome characterisation and sex-specific differences in type 1 and type 2 diabetes mellitus. Cardiovascular Diabetology, 23(1), Article 109. https://doi.org/10.1186/s12933-024-02202-5

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abstract = "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.",

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Barranco-Altirriba, M, Alonso, N, Weber, RJM, Lloyd, GR, Hernandez, M, Yanes, O, Capellades, J, Jankevics, A, Winder, C, Falguera, M, Franch-Nadal, J, Dunn, WB, Perera-Lluna, A, Castelblanco, E & Mauricio, D 2024, 'Lipidome characterisation and sex-specific differences in type 1 and type 2 diabetes mellitus', Cardiovascular Diabetology, vol. 23, no. 1, 109. https://doi.org/10.1186/s12933-024-02202-5

TY - JOUR

T1 - Lipidome characterisation and sex-specific differences in type 1 and type 2 diabetes mellitus

AU - Barranco-Altirriba, Maria

AU - Alonso, Núria

AU - Weber, Ralf J.M.

AU - Lloyd, Gavin R.

AU - Hernandez, Marta

AU - Yanes, Oscar

AU - Capellades, Jordi

AU - Jankevics, Andris

AU - Winder, Catherine

AU - Falguera, Mireia

AU - Franch-Nadal, Josep

AU - Dunn, Warwick B.

AU - Perera-Lluna, Alexandre

AU - Castelblanco, Esmeralda

AU - Mauricio, Didac

PY - 2024/3/29

Y1 - 2024/3/29

N2 - 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.

AB - 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.

KW - Sex-specific differences

KW - Type 1 diabetes

KW - Type 2 diabetes

KW - Untargeted lipidomics

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U2 - 10.1186/s12933-024-02202-5

DO - 10.1186/s12933-024-02202-5

M3 - Article

AN - SCOPUS:85188969893

SN - 1475-2840

VL - 23

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

IS - 1

M1 - 109

ER -

Lipidome characterisation and sex-specific differences in type 1 and type 2 diabetes mellitus

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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