Plasma 1-deoxysphingolipids are early predictors of incident type 2 diabetes mellitus

PLoS One. 2017 May 4;12(5):e0175776. doi: 10.1371/journal.pone.0175776. eCollection 2017.


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/m2). 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.

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Sphingolipids / blood*


  • Biomarkers
  • Blood Glucose
  • Sphingolipids

Grant support

This work was supported by grants from the Zurich Center of Integrated Human Physiology, University of Zurich (ZIHP); the 7th Framework Program of the European Commission (“RESOLVE”, Project number 305707); the Swiss National Foundation SNF (Project 31003A_153390/1); the Hurka Foundation; the Novartis Foundation and the Rare Disease Initiative Zurich (“radiz”, Clinical Research Priority Program for Rare Diseases, University of Zurich) (TH). Further support was obtained from the Swedish Foundation for Medical Research (JM) and from the Swedish Research Council (HBS). The CoLaus study was and is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne and the Swiss National Science Foundation (grants 33CSCO-122661, 33CS30-139468 and 33CS30-148401).