Please use this identifier to cite or link to this item: https://doi.org/10.1172/jci.insight.126925
Title: Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence
Authors: Chew, Wee Siong 
Torta, Federico 
Ji, Shanshan 
Choi, Hyungwon 
Begum, Husna
Sim, Xueling 
Khoo, Chin Meng 
Khoo, Eric Yin Hao 
Ong, Wei-Yi 
Van Dam, Rob M
Wenk, Markus R 
Tai, E Shyong 
Herr, Deron R 
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
CERAMIDE
TYPE-2
METABOLISM
GLYCOSPHINGOLIPIDS
GLUCOSYLCERAMIDE
EXERCISE
REVEALS
ADIPOSE
MODELS
MICE
Issue Date: 2019
Publisher: AMER SOC CLINICAL INVESTIGATION INC
Citation: Chew, Wee Siong, Torta, Federico, Ji, Shanshan, Choi, Hyungwon, Begum, Husna, Sim, Xueling, Khoo, Chin Meng, Khoo, Eric Yin Hao, Ong, Wei-Yi, Van Dam, Rob M, Wenk, Markus R, Tai, E Shyong, Herr, Deron R (2019). Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence. JCI INSIGHT 4 (13). ScholarBank@NUS Repository. https://doi.org/10.1172/jci.insight.126925
Abstract: Copyright: © 2019 American Society for Clinical Investigation BACKGROUND. Sphingolipids (SPs) are ubiquitous, structurally diverse molecules that include ceramides, sphingomyelins (SMs), 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 2302 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 with follow-up visits for 11 years. RESULTS. We found that ceramides correlated positively but hexosylceramides correlated negatively with BMI and homeostatic model assessment of insulin resistance (HOMA-IR). Furthermore, SPs with a d16:1 sphingoid backbone correlated more positively with BMI and HOMA-IR, while d18:2 SPs correlated less positively, relative to canonical d18:1 SPs. We also found that higher concentrations of 2 distinct SMs were associated with a higher risk of T2DM (HR 1.45 with 95% CI 1.18–1.78 for SM d16:1/18:0 and HR 1.40 with 95% CI 1.17–1.68 for SM d18:1/18:0). CONCLUSIONS. We identified significant associations between SPs and obesity/T2DM characteristics, specifically, those of hexosylceramides, d16:1 SPs, and d18:2 SPs. This suggests that the balance of SP metabolism, rather than ceramide accumulation, is associated with the pathology of obesity. We further identified 2 specific SPs that may represent prognostic biomarkers for T2DM. FUNDING. National University Health System (NUHSRO/2014/085/AF-Partner/01) and the National Research Foundation Investigatorship grant (NRF-NRFI2015-05).
Source Title: JCI INSIGHT
URI: https://scholarbank.nus.edu.sg/handle/10635/170375
ISSN: 23793708
23793708
DOI: 10.1172/jci.insight.126925
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