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

Официальное название

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

Обзор

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.

Подробное описание

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

Вмешательства

• Диагностический тест Imaging PET/MRI
  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.
• Диагностический тест Stable isotope infusions
  \[6,6 D2\]-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.
• Диагностический тест meal 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.
• Диагностический тест Indirect calorimetry
  Indirect calorimetry (Vmax Series from Vyaire medical, licence # 22536), measured during10 minutes, every hour.

Первичные конечные точки

• hepatic NEFA uptake [Срок оценки: At baseline of Visit 2 (V2)]

Вторичные конечные точки (12)

• postprandial hepatic Dietary Fatty Acid uptake [Срок оценки: At V2 (from time 0 to +360 minutes)]
• Adipose Tissue DFA trapping and postprandial palmitate flux [Срок оценки: At V2 (from time 0 to +360 minutes)]
• hepatic fatty acid oxidation, esterification and secretion into VLDL [Срок оценки: At baseline]
• Hepatic triglyceride content [Срок оценки: At V2 (-200 minutes)]
• Endogenous Glucose production and meal glucose systemic flux [Срок оценки: At V2 (from time 0 to +360 minutes)]
• Insulin secretion [Срок оценки: At V2 (from time 0 to +360 minutes)]
• Insulin resistance/ sensitivity [Срок оценки: At V2 (from time 0 to +360 minutes)]
• Glycerol turnover [Срок оценки: At visit 2 (from time 0 to +360 minutes)]
• Total substrate utilisation [Срок оценки: At visit 2 (from time 0 to +360 minutes).]
• metabolite response [Срок оценки: At visit 2 (from time 0 to +360 minutes)]
• hormonal response [Срок оценки: At visit 2 (from time 0 to +360 minutes)]
• plasma NEFA NEFA flux [Срок оценки: At visit 2 (from time 0 to +360 minutes)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Канада · 1 центр

• Centre de recherche du CHUS — Sherbrooke

Идентификаторы

NCT: NCT07133854 · 2026-5900

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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