期刊
PLOS ONE
卷 12, 期 5, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0175776
关键词
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资金
- Zurich Center of Integrated Human Physiology, University of Zurich (ZIHP)
- European Commission [305707]
- Swiss National Foundation SNF [31003A_153390/1]
- Hurka Foundation
- Novartis Foundation
- Rare Disease Initiative Zurich (radiz, Clinical Research Priority Program for Rare Diseases, University of Zurich)
- GlaxoSmith Kline
- Faculty of Biology and Medicine of Lausanne
- Swiss National Science Foundation [33CSCO-122661, 33CS30-139468, 33CS30-148401]
1-Deoxysphingolipids (1-deoxySLs) are atypical sphingolipids, which are formed in a side reaction during sphingolipid de-novo synthesis. Recently, we demonstrated that 1-deoxySLs are biomarkers for the prediction of T2DM in obese, non-diabetic patients. Here we investigated the relevance of 1-deoxySLs as long-term predictive biomarkers for the incidence of T2DM in an asymptomatic population. Here, we analyzed the plasma sphingoid base profile in a nested group of non-diabetic individuals (N = 605) selected from a population- based study including 5 year follow-up data (CoLaus study). 1-DeoxySLs at baseline were significantly elevated in individuals who developed T2DM during the follow-up (p<0.001), together with increased glucose (p<5.11E-14), triglycerides (p<0.001)and HOMA-IR indices (p<0.001). 1-Deoxy-sphinganine (1-deoxySA) and 1-deoxy-sphingosine (1-deoxySO) were predictive for T2DM, even after adjusting for fasting glucose levels in the binary regression analyses. The predictive value of the combined markers 1-deoxySA+ glucose were superior to glucose alone in normal-weight subjects (p<0.001) but decreased substantially with increasing BMI. Instead, plasma adiponectin and waist-to-hip ratio appeared to be better risk predictors for obese individuals (BMI>30kg/m(2)). In conclusion, elevated plasma 1-deoxySL levels are strong and independent risk predictors of future T2DM, especially for non-obese individuals in the general population.
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