title: Elevation of plasma 1-deoxy-sphingolipids in type 2 diabetes mellitus: a susceptibility to neuropathy?
abstract: OBJECTIVE
  Diabetic distal sensorimotor polyneuropathy (DSPN) is a frequent, disabling complication of diabetes mellitus. There is increasing evidence that sphingolipids play a role in insulin resistance and type 2 diabetes (T2DM). Whether neurotoxic 1-deoxy-sphingolipids are elevated in DSPN patients' plasma and whether levels correlate to the DSPN stage were examined.
  
  
  METHODS
  The plasma profile of 12 sphingoid bases in patients with DSPN and T2DM(n = 39) were cross-sectionally compared to other nerve disorders including chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 13), transthyretin-related familial amyloid polyneuropathy (FAP) (n = 10), amyotrophic lateral sclerosis (ALS) (n = 13) and small fibre neuropathy (n = 12) by liquid chromatography mass spectrometry. Correlations to the DSPN stage were additionally performed. Furthermore, the sphingoid base distribution in sural nerve specimens was measured in patients with DSPN (n = 6) compared to CIDP (n = 3).
  
  
  RESULTS
  A significantly increased amount of 1-deoxy-sphingolipids [1-deoxy-sphinganine (0.11 ± 0.06 μmol/l), 1-deoxy-sphingosine (0.24 ± 0.16 μmol/l)] in patients with DSPN was observed compared to age-matched healthy controls (0.06 ± 0.03 μmol/l; 0.12 ± 0.05 μmol/l) and to the other groups. (Para)clinical parameters including sensory loss, neuropathic pain, weakness, vibration perception, nerve conduction velocity, sensory nerve action potentials (sural nerve) and duration of T2DM did not correlate with plasma 1-deoxy-sphingolipid levels, neither did the clinical stage according to the Dyck classification for DSPN. Sphingolipid levels in sural nerve biopsies showed no differences between DSPN and CIDP. Contrarily, patients with a small fibre neuropathy had decreased C₂₀-sphingosine plasma levels.
  
  
  CONCLUSIONS
  1-deoxy-sphingolipid plasma levels are significantly elevated in DSPN. They are already detectable in early disease stages but do not correlate with the clinical course. Further knowledge on 1-deoxy-sphingolipids might lead to a better pathophysiological understanding and future treatment options in DSPN.
authors.affiliation: Department of Neurology, RWTH Aachen University, Aachen, Germany; Institute of Neuropathology, RWTH Aachen University, Aachen, Germany.
authors.forename: M F
authors.initials: MF
authors.lastname: Dohrn
authors.forename: A
authors.initials: A
authors.lastname: Othman
authors.forename: S K
authors.initials: SK
authors.lastname: Hirshman
authors.forename: H
authors.initials: H
authors.lastname: Bode
authors.forename: I
authors.initials: I
authors.lastname: Alecu
authors.forename: E
authors.initials: E
authors.lastname: Fähndrich
authors.forename: W
authors.initials: W
authors.lastname: Karges
authors.forename: J
authors.initials: J
authors.lastname: Weis
authors.forename: J B
authors.initials: JB
authors.lastname: Schulz
authors.forename: T
authors.initials: T
authors.lastname: Hornemann
authors.forename: K G
authors.initials: KG
authors.lastname: Claeys
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003929:Diabetic Neuropathies / Q000097:blood*; D004198:Disease Susceptibility; D004916:Erythromelalgia / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011115:Polyneuropathies / Q000097:blood*; D013107:Sphingolipids / Q000097:blood*
chemical_list: D013107:Sphingolipids
keywords: 1-deoxySL; L-serine; atypical sphingolipids; biomarker; deoxysphingolipids; diabetic distal sensorimotor polyneuropathy; polyneuropathy; type 2 diabetes mellitus