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| Name | Class |
|---|---|
| Centre de recherche du Centre hospitalier universitaire de Sherbrooke | OTHER |
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Steatotic liver disease associated with metabolic dysfunction (MASLD) is a disease caused by excess fat storage in the liver. Excessive fat delivery to the liver and MASLD typically occurs in people with abdominal obesity and type 2 diabetes. Type 1 diabetes (T1D) is also associated with a marked increase in the release of fat from adipose tissues and MASLD is increased in T1D and significantly increases the risk of heart, kidney and eye diseases.
It is a parallel study design between T1D and controls. The outcomes will be assessed between T1D vs. controls during the metabolic visit.
The metabolic visit will last 9 hours: it will be a test meal with perfusion of stable tracers, blood sampling, PET acquisitions using radiopharmaceuticals (18FTHA and 11C-palmitate) and MRI acquisitions.
In total, 32 participants will be recruited:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group with Type 1 Diabetes | Experimental | Participants will undergo a 9-hour postprandial metabolic study |
|
| Group without Type 1 Diabetes | Experimental | Participants will undergo a 9-hour postprandial metabolic study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Imaging PET/MRI | Diagnostic Test | MRI using 1H-MRS and Dixon sequences on a 3 T clinical MRI system (Ingenia, Philips Healthcare, Best, the Netherlands) will be performed. [11C]-palmitate: 1 x i.v. injection of 175 MBq followed by TEP imaging. [18F]-FTHA: oral administration of 75 MBq followed by TEP imaging. |
| Measure | Description | Time Frame |
|---|---|---|
| hepatic NEFA uptake | using 11C-palmitate PET | At baseline of Visit 2 (V2) |
| Measure | Description | Time Frame |
|---|---|---|
| postprandial hepatic Dietary Fatty Acid uptake | using 18F-FTHA | At V2 (from time 0 to +360 minutes) |
| Adipose Tissue DFA trapping and postprandial palmitate flux | Determined from the same static (whole-body) acquisition image using oral administration of [18F]-Fluoro-6-Thia- Heptadecanoic Acid (FTHA) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Frédérique Frisch | Contact | +1-819-346-1110 | 12394 | frederique.frisch@usherbrooke.ca |
| Name | Affiliation | Role |
|---|---|---|
| André C Carpentier, MD | Université de Sherbrooke | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre de recherche du CHUS | Sherbrooke | Quebec | J1H 5N4 | Canada |
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|
| Stable isotope infusions | Diagnostic Test | [6,6 D2]-glucose infusion (0.22 µmol/kg/min, preceded by a bolus of 22 µmol/kg) will start from -180 until time + 360. [1,1,2,3,3-2H]-glycerol (0.05 µmol/kg/min.) and of [7,7,8,8-2H] palmitate (0.01 µmol/kg/min) will start from time -60 until time +360. |
|
| meal test | Diagnostic Test | A liquid meal will be administered at time 0. The liquid meal (400 ml) energy breakdown is 50% (101g) from glucose, 33% (31g) from fat, and 17% (40g) from protein; participants will consume the 400 ml in 4 aliquots of 100 ml over 20 min, supplemented with 0.9 g of U-[13C]-glucose and 9 μmol/kg lean mass of [U-13C]-palmitate. |
|
| Indirect calorimetry | Diagnostic Test | Indirect calorimetry (Vmax Series from Vyaire medical, licence # 22536), measured during10 minutes, every hour. |
|
| At V2 (from time 0 to +360 minutes) |
| hepatic fatty acid oxidation, esterification and secretion into VLDL | [11C]-Palmitate PET. Calculated from the same multicompartmental equation using liver [11C]-palmitate kinetics | At baseline |
| Hepatic triglyceride content | measured by MRI | At V2 (-200 minutes) |
| Endogenous Glucose production and meal glucose systemic flux | Apparition rate (µmol/min) of glucose from multicompartimental equation using intravenous perfusion and oral stable isotope tracer | At V2 (from time 0 to +360 minutes) |
| Insulin secretion | Determined by measuring C-peptide kinetics following the liquid meal | At V2 (from time 0 to +360 minutes) |
| Insulin resistance/ sensitivity | Determined by measuring circulating glucose and insulin following the liquid meal: glucose and insulin will be combined to give insulin resistance/sensitivity | At V2 (from time 0 to +360 minutes) |
| Glycerol turnover | calculated from [1,1,2,3,3-2H]-glycerol i.v. | At visit 2 (from time 0 to +360 minutes) |
| Total substrate utilisation | measured by using indirect calorimetry | At visit 2 (from time 0 to +360 minutes). |
| metabolite response | Colorimetric assay | At visit 2 (from time 0 to +360 minutes) |
| hormonal response | Multiplex assay | At visit 2 (from time 0 to +360 minutes) |
| plasma NEFA NEFA flux | calculated from i.v. stable isotope tracer (mass spectrometry). | At visit 2 (from time 0 to +360 minutes) |
| plasma distribution of DFA metabolites | calculated from i.v. and oral stable isotope tracers (mass spectrometry) incorporated into triglyceride-rich lipoproteins and NEFA. | At visit 2 (from time 0 to +360 minutes) |
| Adipose tissue Insulin Resistance index | is calculated from measurement of postabsorptive concentrations of FFAs and insulin. | At visit 2 (from time 0 to +360 minutes) |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D056128 | Obesity, Abdominal |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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