How Abnormal Function of Fat Tissue in Type 1 Diabetes Contributes to Fat in the Liver

Not Applicable

Not yet recruiting

• Conditions: Type 1 Diabetes Mellitus; Metabolic Dysfunction-Associated Steatotic Liver Disease; Non-Alcoholic Steato-Hepatitis (NASH)

• Registration Number: NCT07133854
• Lead Sponsor: Université de Sherbrooke

Brief Summary

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.

Detailed Description

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:

* 16 living with T1D and abdominal obesity

* 16 with normoglycemia

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-08-06
• Study First Submitted QC: 2025-08-13
• Last Update Submitted: 2025-08-13
• Study First Posted: 2025-08-21
• Last Update Posted: 2025-08-21
• Study Start: 2026-09-01
• Primary Completion: 2027-09
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• 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.

Exclusion Criteria

• 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;
• current or planned pregnancy within the next 6 months;
• any contraindication to MRI.
• Being allergic to eggs
• Smoking (>1 cigarette/day) and/or consumption of >2 alcoholic beverages per day
• Having participated to a research study with exposure to radiation in the last year before the start of the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
hepatic NEFA uptake	At baseline of Visit 2 (V2)	using 11C-palmitate PET

Secondary Outcome Measures

Name	Time	Method
postprandial hepatic Dietary Fatty Acid uptake	At V2 (from time 0 to +360 minutes)	using 18F-FTHA
Hepatic triglyceride content	At V2 (-200 minutes)	measured by MRI
Endogenous Glucose production and meal glucose systemic flux	At V2 (from time 0 to +360 minutes)	Apparition rate (µmol/min) of glucose from multicompartimental equation using intravenous perfusion and oral stable isotope tracer
Insulin secretion	At V2 (from time 0 to +360 minutes)	Determined by measuring C-peptide kinetics following the liquid meal
Insulin resistance/ sensitivity	At V2 (from time 0 to +360 minutes)	Determined by measuring circulating glucose and insulin following the liquid meal: glucose and insulin will be combined to give insulin resistance/sensitivity
Adipose Tissue DFA trapping and postprandial palmitate flux	At V2 (from time 0 to +360 minutes)	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	At baseline	\[11C\]-Palmitate PET. Calculated from the same multicompartmental equation using liver \[11C\]-palmitate kinetics
Glycerol turnover	At visit 2 (from time 0 to +360 minutes)	calculated from \[1,1,2,3,3-2H\]-glycerol i.v.
Total substrate utilisation	At visit 2 (from time 0 to +360 minutes).	measured by using indirect calorimetry
metabolite response	At visit 2 (from time 0 to +360 minutes)	Colorimetric assay
hormonal response	At visit 2 (from time 0 to +360 minutes)	Multiplex assay
plasma NEFA NEFA flux	At visit 2 (from time 0 to +360 minutes)	calculated from i.v. stable isotope tracer (mass spectrometry).
plasma distribution of DFA metabolites	At visit 2 (from time 0 to +360 minutes)	calculated from i.v. and oral stable isotope tracers (mass spectrometry) incorporated into triglyceride-rich lipoproteins and NEFA.
Adipose tissue Insulin Resistance index	At visit 2 (from time 0 to +360 minutes)	is calculated from measurement of postabsorptive concentrations of FFAs and insulin.

Trial Locations

Locations (1)

Centre de recherche du CHUS; 🇨🇦 Sherbrooke, Quebec, Canada