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.
16 individuals living with T1D and abdominal obesity, as defined by the International Diabetes Federation country/ethnic group-specific criteria (https://www.idf.org/e-library/consensus-statements/60- [1]. Treatment for T1D will be intensive insulin therapy on continuous pump perfusion with continuous glucose monitoring.
16 individuals with normoglycemia (i.e., HbA1c below 6.0%) matched for sex, age (± 5 years), waist circumference (± 3 cm), and menopausal status.
less than 70% of time in glycemic range (for T1D);
history of primary dyslipidemia (LDL-cholesterol over 5 mmol/L or TG over 10 mmol/L) or uncontrolled high blood pressure (over 160/100 mmHg) precluding the withdrawal of lipid lowering and anti-hypertensive agents as per protocol;
presence of overt cardiovascular, liver or renal disease (except microalbuminuria without reduced kidney function), or other uncontrolled medical conditions;
use of any medication other than insulin that may affect lipid or carbohydrate metabolism and that cannot be stopped prior to testing;
Parallel
Imaging PET/MRI
Diagnostic testMRI 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.
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 testA 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 testIndirect calorimetry (Vmax Series from Vyaire medical, licence # 22536), measured during10 minutes, every hour.
hepatic NEFA uptake
using 11C-palmitate PET
postprandial hepatic Dietary Fatty Acid uptake
using 18F-FTHA
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)
hepatic fatty acid oxidation, esterification and secretion into VLDL
\[11C\]-Palmitate PET. Calculated from the same multicompartmental equation using liver \[11C\]-palmitate kinetics
Hepatic triglyceride content
measured by MRI
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Université de Sherbrooke
Lead sponsor
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Collaborator
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