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Metabolism
Plasma 1-deoxysphingolipids are predictive biomarkers for type 2 diabetes mellitus
  1. Alaa Othman1,2,3,
  2. Christoph H Saely4,5,6,
  3. Axel Muendlein4,5,6,
  4. Alexander Vonbank4,5,6,
  5. Heinz Drexel4,5,6,7,
  6. Arnold von Eckardstein1,2,
  7. Thorsten Hornemann1,2
  1. 1Institute for Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland
  2. 2Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
  3. 3Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany
  4. 4Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
  5. 5Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
  6. 6Private University of the Principality of Liechtenstein, Triesen, Liechtenstein
  7. 7Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
  1. Correspondence to Dr Thorsten Hornemann; thorsten.hornemann{at}usz.ch

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.

Research design and 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.

  • Biomarkers
  • Amino Acid
  • Serum Lipids
  • Sciatic Nerves

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjdrc-2014-000073

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