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Significant abnormalities of the HDL phosphosphingolipidome in type 1 diabetes despite normal HDL cholesterol
Damien Denimal1, Jean-Paul Pais de Barros2, Jean-Michel Petit3
1National 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.
Insights
Type 1 diabetes alters HDL lipid profiles, decreasing sphingosine-1-phosphate (S1P) and ceramides despite normal HDL cholesterol. These changes may explain impaired HDL function in diabetic patients.
Area of Science:
- Lipidomics
- Cardiovascular Research
- Metabolic Disorders
Background:
- High-density lipoprotein (HDL) is crucial for cardiovascular health, with phospholipids and sphingolipids mediating its protective functions.
- HDL functionality is compromised in individuals with type 1 diabetes mellitus (T1DM).
Purpose of the Study:
- To investigate alterations in the phospholipid and sphingolipid profiles of HDL in patients with T1DM.
- To determine if these lipid changes occur independently of HDL cholesterol levels.
Main Methods:
- Liquid chromatography-tandem mass spectrometry was employed to quantify various lipid species in HDL2 and HDL3 fractions.
- The study included 54 T1DM patients and 50 healthy controls.
Main Results:
- HDL cholesterol levels were comparable between T1DM patients and controls.
- Sphingosine-1-phosphate (S1P) and ceramide levels were significantly reduced in the HDL of T1DM patients.
- Decreased concentrations of S1P and ceramides were also observed in the total plasma and non-HDL fractions of T1DM patients.
Conclusions:
- Individuals with T1DM exhibit an impaired HDL phospholipid and sphingolipid profile, even with normal HDL cholesterol.
- The observed reduction in S1P may contribute to the diminished HDL functionality seen in T1DM.
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.
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