Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence.
JCI Insight
; 52019 06 04.
Article
em En
| MEDLINE
| ID: mdl-31162145
ABSTRACT
BACKGROUND:
Sphingolipids (SPs) are ubiquitous, structurally diverse molecules that include ceramides, sphingomyelins, and sphingosines. They are involved in various pathologies including obesity and type 2 diabetes mellitus (T2DM). Therefore, it is likely that perturbations in plasma concentrations of SPs are associated with disease. Identifying these associations may reveal useful biomarkers or provide insight into disease processes.METHODS:
We performed a lipidomics evaluation of molecularly-distinct SPs in the plasma of 2,302 ethnically-Chinese Singaporeans using electrospray ionization mass spectrometry coupled with liquid chromatography. SP profiles were compared to clinical and biochemical characteristics, and subjects were evaluated by follow-up visits for 11 years.RESULTS:
We found that ceramides correlate positively but hexosylceramides correlate negatively with body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA-IR). Furthermore, SPs with a d161 sphingoid backbone correlate more positively with BMI and HOMA-IR, while d182 SPs correlate less positively, relative to canonical d181 SPs. We also found that higher concentrations of two distinct sphingomyelins were associated with a higher risk of T2DM (HR 1.45, 95% CI 1.18-1.78 for SM d161/C180; and HR 1.40, 95% CI 1.17-1.68 for SM d181/C180).CONCLUSION:
We identified significant associations between SPs and obesity/T2DM characteristics, specifically, that of hexosylceramides, d161 SPs, and d182 SPs. This suggests that the balance of SP metabolism, rather than ceramide accumulation, is associated with the pathology of obesity. We further identified two specific SPs that may represent prognostic biomarkers for T2DM.FUNDING:
Funding sources are listed in the Acknowledgements section.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esfingolipídeos
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Diabetes Mellitus Tipo 2
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Lipidômica
Tipo de estudo:
Incidence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2019
Tipo de documento:
Article