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Open Access 01-12-2024 | Type 2 Diabetes | Research

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

Authors: 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

Published in: Cardiovascular Diabetology | Issue 1/2024

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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Title: Lipidome characterisation and sex-specific differences in type 1 and type 2 diabetes mellitus
Authors: 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
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Type 2 Diabetes
Type 1 Diabetes
Prediabetes
Published in: Cardiovascular Diabetology / Issue 1/2024
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/s12933-024-02202-5

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Abstract

Background

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