Significant abnormalities of the HDL phosphosphingolipidome in type 1 diabetes despite normal HDL cholesterol concentration

Atherosclerosis. 2015 Aug;241(2):752-60. doi: 10.1016/j.atherosclerosis.2015.06.040. Epub 2015 Jun 29.

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).

Conclusion: 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.

Keywords: HDL; Lipidomics; Plasmalogens; Sphingosine-1-phosphate; Tandem mass spectrometry; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ceramides / chemistry*
  • Cholesterol, HDL / blood*
  • Chromatography, Liquid
  • Diabetes Mellitus, Type 1 / blood*
  • Female
  • Humans
  • Lipids / chemistry
  • Lipoproteins, HDL / blood*
  • Lysophospholipids / chemistry
  • Male
  • Middle Aged
  • Phospholipids / chemistry
  • Plasmalogens / chemistry
  • Sphingolipids / metabolism*
  • Sphingosine / analogs & derivatives
  • Sphingosine / chemistry
  • Tandem Mass Spectrometry

Substances

  • Ceramides
  • Cholesterol, HDL
  • Lipids
  • Lipoproteins, HDL
  • Lysophospholipids
  • Phospholipids
  • Plasmalogens
  • Sphingolipids
  • sphingosine 1-phosphate
  • Sphingosine