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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Type 2 Diabetes | Research

Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes

Authors: Qi Chen, Wei Wang, Ming-Feng Xia, You-li Lu, Hua Bian, Chen Yu, Xiao-Ying Li, Mathew A. Vadas, Xin Gao, Huan-Dong Lin, Pu Xia

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Background

Sphingosine Kinase (SphK) that catalyzes sphingosine (Sph) to sphingosine 1-phosphate (S1P), plays a key role in both sphingolipid metabolism and cellular signaling. While SphK has been implicated in type 2 diabetes mellitus (T2DM), it is unexplored in humans. Herein, we investigated whether circulating SphK-related metabolites are associated with T2DM incidence in an established prospective cohort.

Methods

Levels of SphK-related sphingolipid metabolites, including Sph, S1P, dihydrosphingosine (dhSph) and dihydro-S1P (dhS1P) in serum were measured by targeted-lipidomic analyses. By accessing to an established prospective cohort that involves a total of 2486 non-diabetic adults at baseline, 100 subjects who developed T2DM after a mean follow-up of 4.2-years, along with 100 control subjects matched strictly with age, sex, BMI and fasting glucose, were randomly enrolled for the present study.

Results

Comparison with the control group, medians of serum dhS1P and dhS1P/dhSph ratio at baseline were elevated significantly prior to the onset of T2DM. Each SD increment of dhS1P and dhS1P/dhSph ratio was associated with 53.5% and 54.1% increased risk of incident diabetes, respectively. The predictive effect of circulating dhS1P and dhS1P/dhSph ratio on T2DM incidence was independent of conventional risk factors in multivariate regression models. Furthermore, combination of serum dhS1P and dhS1P/dhSph ratio with conventional clinical indices significantly improved the accuracy of T2DM prediction (AUROC, 0.726), especially for normoglycemic subjects (AUROC, 0.859).

Conclusion

Circulating levels of dhS1P and dhS1P/dhSph ratio are strongly associated with increased risk of T2DM, and could serve as a useful biomarker for prediction of incident T2DM in normoglycemic populations.
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Metadata
Title
Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes
Authors
Qi Chen
Wei Wang
Ming-Feng Xia
You-li Lu
Hua Bian
Chen Yu
Xiao-Ying Li
Mathew A. Vadas
Xin Gao
Huan-Dong Lin
Pu Xia
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Type 2 Diabetes
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-03066-z

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