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

NCT07133854 | Not Yet Recruiting

• 1 other identifier: 2026-5900
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

abdominal obesity; Adipose tissue insulin resistance

Outcome Measures

Primary Outcomes (1)

• hepatic NEFA uptake

  using 11C-palmitate PET

  At baseline of Visit 2 (V2)

Secondary Outcomes (14)

• postprandial hepatic Dietary Fatty Acid uptake

  At V2 (from time 0 to +360 minutes)

• Adipose Tissue DFA trapping and postprandial palmitate flux

  At V2 (from time 0 to +360 minutes)

• hepatic fatty acid oxidation, esterification and secretion into VLDL

  At baseline

• Hepatic triglyceride content

  At V2 (-200 minutes)

• Endogenous Glucose production and meal glucose systemic flux

  At V2 (from time 0 to +360 minutes)

Study Arms (2)

Group with Type 1 Diabetes

EXPERIMENTAL

Participants will undergo a 9-hour postprandial metabolic study

Diagnostic Test: Imaging PET/MRI; Diagnostic Test: Stable isotope infusions; Diagnostic Test: meal test; Diagnostic Test: Indirect calorimetry

Group without Type 1 Diabetes

EXPERIMENTAL

Participants will undergo a 9-hour postprandial metabolic study

Diagnostic Test: Imaging PET/MRI; Diagnostic Test: Stable isotope infusions; Diagnostic Test: meal test; Diagnostic Test: Indirect calorimetry

Interventions

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.

Group with Type 1 Diabetes; Group without Type 1 Diabetes

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.

Group with Type 1 Diabetes; Group without Type 1 Diabetes

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.

Group with Type 1 Diabetes; Group without Type 1 Diabetes

Indirect calorimetry DIAGNOSTIC_TEST

Indirect calorimetry (Vmax Series from Vyaire medical, licence # 22536), measured during10 minutes, every hour.

Group with Type 1 Diabetes; Group without Type 1 Diabetes

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• individuals with normoglycemia (i.e., HbA1c below 6.0%) matched for sex, age (± 5 years), waist circumference (± 3 cm), and menopausal status.

You may not qualify if:

• 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

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Centre de recherche du Centre hospitalier universitaire de Sherbrooke: collaborator

Study Sites (1)

Centre de recherche du CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Obesity, Abdominal

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• André C Carpentier, MD

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frédérique Frisch

CONTACT

+1-819-346-1110; frederique.frisch@usherbrooke.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Tenure professor

Study Record Dates

• First Submitted: August 6, 2025
• First Posted: August 21, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: August 21, 2025

Record last verified: 2025-07

Locations

CA (1)