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

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

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.

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

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