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NCT Number: NCT07133854

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

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.

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Key information

Age range

21 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Centre de recherche du CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

Location contact

André C Carpentier, MD

PRINCIPAL_INVESTIGATOR

Frédérique Frisch

CONTACT

[email protected]

+1-819-346-1110 ext. 12394

About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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.

Primary outcomes

  1. hepatic NEFA uptake

    Time frame: At baseline of Visit 2 (V2)

    using 11C-palmitate PET

Secondary outcomes

  1. postprandial hepatic Dietary Fatty Acid uptake

    Time frame: At V2 (from time 0 to +360 minutes)

    using 18F-FTHA

  2. Adipose Tissue DFA trapping and postprandial palmitate flux

    Time frame: 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)

  3. hepatic fatty acid oxidation, esterification and secretion into VLDL

    Time frame: At baseline

    [11C]-Palmitate PET. Calculated from the same multicompartmental equation using liver [11C]-palmitate kinetics

  4. Hepatic triglyceride content

    Time frame: At V2 (-200 minutes)

    measured by MRI

  5. Endogenous Glucose production and meal glucose systemic flux

    Time frame: 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

  6. Insulin secretion

    Time frame: At V2 (from time 0 to +360 minutes)

    Determined by measuring C-peptide kinetics following the liquid meal

  7. Insulin resistance/ sensitivity

    Time frame: 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

  8. Glycerol turnover

    Time frame: At visit 2 (from time 0 to +360 minutes)

    calculated from [1,1,2,3,3-2H]-glycerol i.v.

  9. Total substrate utilisation

    Time frame: At visit 2 (from time 0 to +360 minutes).

    measured by using indirect calorimetry

  10. metabolite response

    Time frame: At visit 2 (from time 0 to +360 minutes)

    Colorimetric assay

  11. hormonal response

    Time frame: At visit 2 (from time 0 to +360 minutes)

    Multiplex assay

  12. plasma NEFA NEFA flux

    Time frame: At visit 2 (from time 0 to +360 minutes)

    calculated from i.v. stable isotope tracer (mass spectrometry).

  13. plasma distribution of DFA metabolites

    Time frame: 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.

  14. Adipose tissue Insulin Resistance index

    Time frame: At visit 2 (from time 0 to +360 minutes)

    is calculated from measurement of postabsorptive concentrations of FFAs and insulin.

Study contacts

Contact information is provided by the study sponsor or research team.

Frédérique Frisch

CONTACT

[email protected]

+1-819-346-1110 ext. 12394

Sponsors and collaborators

Lead sponsor

Université de Sherbrooke

Other

Collaborators

  • Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Registry information

Official study title

The Impact of Adipose Tissue Insulin Resistance and Abdominal Obesity on Hepatic Fatty Acid Metabolism in Type 1 Diabetes

Acronym: AGL14

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
Aug 21, 2025
Registry last updated
Aug 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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