Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes
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 investig...
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doaj-fb6ba8d766b541318aaf1d3fd0bd73362021-09-19T11:08:16ZengBMCJournal of Translational Medicine1479-58762021-09-0119111110.1186/s12967-021-03066-zIdentification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetesQi Chen0Wei Wang1Ming-Feng Xia2You-li Lu3Hua Bian4Chen Yu5Xiao-Ying Li6Mathew A. Vadas7Xin Gao8Huan-Dong Lin9Pu Xia10Department of Endocrinology and Metabolism, Fudan Institute for Metabolic Diseases, Zhongshan Hospital, Fudan UniversityDepartment of Endocrinology and Metabolism, Fudan Institute for Metabolic Diseases, Zhongshan Hospital, Fudan UniversityDepartment of Endocrinology and Metabolism, Fudan Institute for Metabolic Diseases, Zhongshan Hospital, Fudan UniversityCentral Laboratory, Xuhui Central HospitalDepartment of Endocrinology and Metabolism, Fudan Institute for Metabolic Diseases, Zhongshan Hospital, Fudan UniversityCentral Laboratory, Xuhui Central HospitalDepartment of Endocrinology and Metabolism, Fudan Institute for Metabolic Diseases, Zhongshan Hospital, Fudan UniversityCentenary Institute, The University of SydneyDepartment of Endocrinology and Metabolism, Fudan Institute for Metabolic Diseases, Zhongshan Hospital, Fudan UniversityDepartment of Endocrinology and Metabolism, Fudan Institute for Metabolic Diseases, Zhongshan Hospital, Fudan UniversityDepartment of Endocrinology and Metabolism, Fudan Institute for Metabolic Diseases, Zhongshan Hospital, Fudan UniversityAbstract 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.https://doi.org/10.1186/s12967-021-03066-z |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes Journal of Translational Medicine |
author_facet |
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 |
author_sort |
Qi Chen |
title |
Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes |
title_short |
Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes |
title_full |
Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes |
title_fullStr |
Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes |
title_full_unstemmed |
Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes |
title_sort |
identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2021-09-01 |
description |
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. |
url |
https://doi.org/10.1186/s12967-021-03066-z |
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