title: Significant abnormalities of the HDL phosphosphingolipidome in type 1 diabetes despite normal HDL cholesterol concentration.
abstract: OBJECTIVE
  Phospholipids and sphingolipids are major components of HDL. They play a critical role in HDL functionality and protective effects against atherosclerosis. As HDL are dysfunctional in type 1 diabetic patients, we ascertained whether they presented abnormalities in their phospholipid and sphingolipid profile, despite normal HDL cholesterol concentration.
  
  
  METHODS
  Using liquid chromatography-tandem mass spectrometry, we quantified the main species of phosphatidylcholines, sphingomyelins, lysophophatidylcholines, phosphatidylethanolamines, phosphatidylinositols, ceramides, plasmalogens and sphingosines 1-phosphate in the HDL2 and HDL3 from 54 type 1 diabetic patients and 50 controls.
  
  
  RESULTS
  Serum HDL cholesterol was similar in the 2 groups of subjects. When data were expressed relative to the total amount of phospholipids and sphingolipids, sphingosines-1-phosphate (S1P) were 11.7% (NS) and 14.4% (p = 0.0062) lower in HDL2 and HDL3, respectively, from type 1 diabetic patients than from controls. Ceramides were 23% (p = 0.005) and 24% (borderline significance) lower in HDL2 and HDL3, respectively. The concentration of apolipoprotein M, the carrier of S1P, was similar in patients and controls. In type 1 diabetic patients compared to controls, the concentration of d18:1-S1P, the main S1P species, was decreased in total plasma (-17.0%, p < 0.0001), HDL fraction (-21.9%, p < 0.0001) and non-HDL fraction (-13.7%, p = 0.012). The concentration of ceramides was decreased in total plasma (-24.4%, p < 0.0001), HDL fraction (-27.9%, p = 0.0006) and non-HDL fraction (-22.0%, p = 0.0087).
  
  
  CONCLUSIONS
  Despite normal HDL cholesterol level, the phospholipid + sphingolipid profile is impaired in HDL from type 1 diabetic patients. These abnormalities, especially the decrease in S1P, could contribute to the impaired HDL functionality observed in these patients.
authors.affiliation: National Institut of Health and Medical Research (INSERM) Unit 866-University Bourgogne-Franche Comté, Bâtiment B3, 15 B(d) M(al) de Lattre de Tassigny, 21000 Dijon, France; Department of Biochemistry, University Hospital, 2 rue Angélique Ducoudray, BP 37013, 21070 Dijon, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Denimal
authors.affiliation: Lipidomic Platform, National Institut of Health and Medical Research (INSERM) Unit 866-University Bourgogne-Franche Comté, Bâtiment B(3), 15 B(d) M(al) de Lattre de Tassigny, 21000 Dijon, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pais de Barros
authors.affiliation: National Institut of Health and Medical Research (INSERM) Unit 866-University Bourgogne-Franche Comté, Bâtiment B3, 15 B(d) M(al) de Lattre de Tassigny, 21000 Dijon, France; Department of Endocrinology and Metabolic Diseases, University Hospital Bocage Central, 14 rue Gaffarel, 21000 Dijon, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Petit
authors.affiliation: National Institut of Health and Medical Research (INSERM) Unit 866-University Bourgogne-Franche Comté, Bâtiment B3, 15 B(d) M(al) de Lattre de Tassigny, 21000 Dijon, France; Department of Endocrinology and Metabolic Diseases, University Hospital Bocage Central, 14 rue Gaffarel, 21000 Dijon, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bouillet
authors.affiliation: National Institut of Health and Medical Research (INSERM) Unit 866-University Bourgogne-Franche Comté, Bâtiment B3, 15 B(d) M(al) de Lattre de Tassigny, 21000 Dijon, France; Department of Endocrinology and Metabolic Diseases, University Hospital Bocage Central, 14 rue Gaffarel, 21000 Dijon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vergès
authors.affiliation: National Institut of Health and Medical Research (INSERM) Unit 866-University Bourgogne-Franche Comté, Bâtiment B3, 15 B(d) M(al) de Lattre de Tassigny, 21000 Dijon, France; Department of Biochemistry, University Hospital, 2 rue Angélique Ducoudray, BP 37013, 21070 Dijon, France. Electronic address: laurence.duvillard@chu-dijon.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Duvillard
mesh_terms: D000328:Adult; D002518:Ceramides / Q000737:chemistry*; D008076:Cholesterol, HDL / Q000097:blood*; D002853:Chromatography, Liquid; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000097:blood*; D008246:Lysophospholipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000737:chemistry; D010955:Plasmalogens / Q000737:chemistry; D013107:Sphingolipids / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D002518:Ceramides; D008076:Cholesterol, HDL; D008055:Lipids; D008075:Lipoproteins, HDL; D008246:Lysophospholipids; D010743:Phospholipids; D010955:Plasmalogens; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: HDL; Lipidomics; Plasmalogens; Sphingosine-1-phosphate; Tandem mass spectrometry; Type 1 diabetes