title: Deoxysphingoid bases as plasma markers in diabetes mellitus.
abstract: BACKGROUND
  Sphingoid bases are formed from the precursors L-serine and palmitoyl-CoA-a reaction which is catalyzed by the serine-palmitoyltransferase (SPT). SPT metabolizes, besides palmitoyl-CoA also other acyl-CoAs but shows also variability towards the use of other amino acid substrates. The enzyme is also able to metabolize alanine, which results in the formation of an atypical deoxy-sphingoid base (DSB). This promiscuous activity is greatly increased in the case of the sensory neuropathy HSAN1, and pathologically elevated DSB levels have been identified as the cause of this disease. Clinically, HSAN1 shows a pronounced similarity to the diabetic sensory neuropathy (DSN), which is the most common chronic complication of diabetes mellitus. Since serine and alanine metabolism is functionally linked to carbohydrate metabolism by their precursors 3-phosphoglycerate and pyruvate, we were interested to see whether the levels of certain sphingoid base metabolites are altered in patients with diabetes.
  
  
  RESULTS
  In a case-control study we compared plasma sphingoid base levels between healthy and diabetic individuals. DSB levels were higher in the diabetic group whereas C16 and C18 sphingoid bases were not significantly different. Plasma serine, but not alanine levels were lower in the diabetic group. A subsequent lipoprotein fractionation showed that the DSBs are primarily present in the LDL and VLDL fraction.
  
  
  CONCLUSIONS
  Our results suggest that DSBs are a novel category of plasma biomarkers in diabetes which reflect functional impairments of carbohydrate metabolism. Furthermore, elevated DSB levels as we see them in diabetic patients might also contribute to the progression of the diabetic sensory neuropathy, the most frequent complication of diabetes.
authors: Institute for Clinical Chemistry, University Hospital Zurich and Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors: Mariana
authors: M
authors: Bertea
authors: Markus F
authors: MF
authors: Rütti
authors: Alaa
authors: A
authors: Othman
authors: Jaqueline
authors: J
authors: Marti-Jaun
authors: Martin
authors: M
authors: Hersberger
authors: Arnold
authors: A
authors: von Eckardstein
authors: Thorsten
authors: T
authors: Hornemann
mesh_terms: D000368:Aged; D000409:Alanine / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000097:blood* / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D012694:Serine / Q000097:blood; D013107:Sphingolipids / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers; D008074:Lipoproteins; D013107:Sphingolipids; D012694:Serine; D013110:Sphingosine; D000409:Alanine