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

- In type 1 diabetes, HDL phosphosphingolipidome show abnormalities despite normal HDL cholesterol concentration.
- HDL sphingosines-1-phosphate and ceramides are decreased.
- These decreases are related to a decrease in total plasma and in the non-HDL fraction.
- The decrease in sphingosines-1-phosphate may contribute to impaired HDL functionality.

ObjectivePhospholipids 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.MethodsUsing 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.ResultsSerum 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).ConclusionDespite 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.