title: Plasma 1-deoxysphingolipids are predictive biomarkers for type 2 diabetes mellitus.
abstract: OBJECTIVE
  Serine palmitoyltransferase (SPT) catalyzes the condensation of serine and palmitoyl coenzyme A, the first step in the de novo sphingolipid synthesis. Apart from these canonical substrates, SPT can also metabolize alanine and other acyl coenzyme As. This forms a spectrum of atypical sphingoid bases which are altered in the context of the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). We investigated whether atypical sphingolipids can be used as prospective markers to predict the incidence of T2DM.
  
  
  METHODS
  Using liquid chromatography/mass spectrometry, we analyzed the sphingoid base profile in a prospective cohort with 339 individuals. All individuals were followed up for a period of 8 years.
  
  
  RESULTS
  Confirming earlier results, we found 1-deoxysphingolipids (1-deoxySLs) to be significantly elevated in patients with MetS, impaired fasting glucose, and T2DM. Patients who developed T2DM during the follow-up period (n=32) showed significantly higher 1-deoxySL levels at baseline compared with those who did not develop T2DM until the end of the study (n=70). 1-Deoxysphingosine levels were independent predictors for T2DM even after adjusting for glycated hemoglobin (standardized adjusted OR=2.1, CI 95% (1.19 to 3.71); p=0.010), MetS (standardized adjusted OR=1.97, CI 95% (1.13 to 3.43); p=0.017), and other risk factors such as age, sex, BMI, and lipid-lowering drugs. Similar results were observed for the 1-deoxysphinganine levels.
  
  
  CONCLUSIONS
  Our results support a novel role for 1-deoxySL as predictive biomarkers for the development of T2DM in risk patients and warrants further larger prospective trials in lower risk cohorts.
authors: Institute for Clinical Chemistry, University Hospital Zurich , Zurich , Switzerland ; Centre for Integrative Human Physiology, University of Zurich , Zurich , Switzerland ; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck , Lübeck , Germany.
authors: Alaa
authors: A
authors: Othman
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT) , Feldkirch , Austria ; Department of Medicine and Cardiology , Academic Teaching Hospital Feldkirch , Feldkirch , Austria ; Private University of the Principality of Liechtenstein , Triesen , Liechtenstein.
authors: Christoph H
authors: CH
authors: Saely
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT) , Feldkirch , Austria ; Department of Medicine and Cardiology , Academic Teaching Hospital Feldkirch , Feldkirch , Austria ; Private University of the Principality of Liechtenstein , Triesen , Liechtenstein.
authors: Axel
authors: A
authors: Muendlein
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT) , Feldkirch , Austria ; Department of Medicine and Cardiology , Academic Teaching Hospital Feldkirch , Feldkirch , Austria ; Private University of the Principality of Liechtenstein , Triesen , Liechtenstein.
authors: Alexander
authors: A
authors: Vonbank
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT) , Feldkirch , Austria ; Department of Medicine and Cardiology , Academic Teaching Hospital Feldkirch , Feldkirch , Austria ; Private University of the Principality of Liechtenstein , Triesen , Liechtenstein ; Drexel University College of Medicine , Philadelphia, Pennsylvania , USA.
authors: Heinz
authors: H
authors: Drexel
authors: Institute for Clinical Chemistry, University Hospital Zurich , Zurich , Switzerland ; Centre for Integrative Human Physiology, University of Zurich , Zurich , Switzerland.
authors: Arnold
authors: A
authors: von Eckardstein
authors: Institute for Clinical Chemistry, University Hospital Zurich , Zurich , Switzerland ; Centre for Integrative Human Physiology, University of Zurich , Zurich , Switzerland.
authors: Thorsten
authors: T
authors: Hornemann
keywords: Amino Acid; Biomarkers; Sciatic Nerves; Serum Lipids