Plasma Dihydroceramides Are Associated With Hepatic Steatosis in Type 1 and Type 2 Diabetes

Study Overview
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Brief Summary
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Sphingolipids are associated with metabolic diseases. Distribution of plasma sphingolipids in type 1 and type 2 diabetes has never been studied. The objective of the CERADIAB study is to compare plasma sphingoliplids concentrations in type 1 and type 2 diabetic patients.

Detailed Description
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Sphingolipids represent a major class of lipids that are structural and signaling molecules. Major bioactive sphingolipids include ceramide, dihydroceramide, sphingosine, sphingosine-1-phosphate and sphingomyelin. Sphingoliplids are involved in development of various chronic metabolic diseases. Some ceramides species are implicated in pancreatic β-cell apoptosis and in insulin resistance in muscle, fat and liver. Some studies have shown association between inhibition of ceramide synthesis, insulin sensibility and lower hepatic steatosis. The deposition of hepatic lipids, especially triacylglycerol, defines the development of hepatic steatosis. However, sphingolipids appear to play an important role in non-alcoholic fatty liver disease (NAFLD) and in its progression. Changes in plasma shingolipids concentrations may also contribute to the pathogenesis in cardiovascular disease and atherosclerosis. Distribution of plasma sphingolipids concentrations in type 1 and type 2 diabetes has poorly been studied. The objective of the CERADIAB study is to compare plasma sphingoliplids concentrations in type 1 and type 2 diabetic patients.

Official Title
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Plasma Dihydroceramides Are Associated With Hepatic Steatosis in Type 1 and Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Other: dosing of sphingolipids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 1 or 2 diabetes Exclusion Criteria: atypical diabetes family dyslipidemia nonmetabolic hepatopathy severe renal failure corticosteroid or immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Type 1 diabetes<br>dosing of sphingolipids | Other: dosing of sphingolipids<br>* - Measuring the concentration of many species of sphingomyelins, ceramides, dihydroceramides and sphingosine<br>|
| Type 2 diabetes<br>Dosing of sphingolipids | Other: dosing of sphingolipids<br>* - Measuring the concentration of many species of sphingomyelins, ceramides, dihydroceramides and sphingosine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of plasma total ceramides concentration in type 2 diabetic patients versus type 1 diabetic patients. | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Comparison of plasma total dihydroceramides concentration in type 2 diabetic patients versus type 1 diabetic patients. | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 
| - - Comparison of plasma total sphingomyelins concentration in type 2 diabetic patients versus type 1 diabetic patients. | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 
| - Comparison of plasma total sphingosine concentration in type 2 diabetic patients versus type 1 diabetic patients. | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 
| - Comparison of plasma ceramide species (C16, C18, C20, C22, C23, C24, C24:1, C26:1, C26:2 ceramides) concentration in type 2 diabetic patients versus type 1 diabetic patients. | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 
| - Comparison of plasma dihydroceramide species (C18/16, C18/18, C18/20, C18/22, C18/23, C18/24, C18/24:1, C18/26:1, C18/26:2 dihydroceramides) concentration in type 2 diabetic patients versus type 1 diabetic patients. | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 
| - Correlation between sphingolipids species concentrations and NAFLD biomarkers (steatotest, NASHtest and fibrotest) | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 
| - Correlation between sphingolipids species concentrations and insulin resistance (HOMA-IR) | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 
| - Correlation between sphingolipids species concentrations and microvascular complications (history of retinopathy, nephropathy and neuropathy) | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 
| - Correlation between sphingolipids species concentrations and macrovascular complications (cardiovascular disease history) | Three-hundred microlitres of plasma were used to quantify dihydroceramides, ceramides, sphingomyelins and sphingosine content. The lipid subspecies were extracted and analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS), at the Lipidomic Core Facility of the University of Bourgogne (Dijon, France). | Samples taken in 1 single time in the morning, patients fast for 12 hours, on 1 single day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sphingolipids, hepatic steatosis, non-alcoholic fatty liver disease, macrovascular complications, insulin resistance, microvasclar complications, NAFLD