Aún no reclutaNCT07927647Registro de ClinicalTrials.gov

Immunological Signatures of MASLD and MASH in Patients With Type 1 Diabetes

Type 1 Diabetes Mellitus (T1D) · Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) · Metabolic Dysfunction-Associated Steatohepatitis (MASH) · Type 2 Diabetes Mellitus (T2D)

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LO ESENCIAL

De qué trata este estudio

El registro no identifica actualmente este estudio como reclutando. Consulta su estado antes de planificar una evaluación.

Tipo de estudio: Observacional
Fase: No aplica / no indicada
Rango de edad: 18 años - No especificado
Sexo admitido: Todos los sexos
Voluntarios sanos: No aceptados
Participantes: 1000 Estimado

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Las explicaciones y la navegación están en español. Los textos proporcionados por el registro, incluidos títulos, resúmenes y criterios, se conservan en su idioma original. Puedes pedir orientación en español a WCR.

Acerca de la investigación

MASLD and its inflammatory form, MASH, are major public health concerns due to their high prevalence and association with hepatic and cardiovascular morbidity and mortality. Although extensively studied in type 2 diabetes (T2D), their pathophysiology in type 1 diabetes (T1D) remains poorly understood. Given the differences in immune mechanisms between T1D, primarily involving adaptive immunity, and T2D, associated with chronic innate immune activation, MASH may involve distinct immunoinflammatory pathways depending on the type of diabetes. This cross-sectional study aims to identify specific immunological and transcriptomic signatures associated with MASLD/MASH in patients with T1D and compare them with those observed in T2D, ultimately improving understanding of disease mechanisms and hepatic and cardiovascular risk stratification.

Leer la descripción completa

Background : Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are associated with liver-related and cardiovascular morbidity. Although these conditions have been extensively investigated in type 2 diabetes (T2D), their immune mechanisms in type 1 diabetes (T1D) remain insufficiently characterized. The differences between the adaptive immune response involved in T1D and the low-grade innate inflammation frequently associated with T2D may result in distinct immunoinflammatory signatures.
Objectives :

The primary objective is to identify and characterize immunological and transcriptomic signatures associated with MASH in adults living with T1D, by comparing circulating immune-cell profiles according to liver status (no steatosis, MASLD without MASH, or MASH).
The secondary objectives include estimating the MASLD/MASH prevalence, identifying associated clinical and metabolic factors, defining inflammatory endotypes, investigating associations with cardiovascular risk and diabetic foot complications, and comparing signatures with existing T2D data from the AngioSafe T2D cohort.
Design : This is a multicenter, non-interventiona and cross-sectional observational study, conducted at the diabetology departments of Lariboisière and Bichat hospitals, Assistance Publique-Hôpitaux de Paris (AP-HP), France. Adults living with T1D attending a scheduled day-hospital visit that includes routine FibroScan assessment will be consecutively screened. The T2D comparator consists of previously collected data from participants in the AngioSafe T2D cohort.
Procedures : After participant information and verbal non-opposition, clinical, metabolic, biological and hepatic data will be obtained from routine care records. Liver steatosis and stiffness are assessed by transient elastography (FibroScan).

An additional 14 mL of peripheral venous blood (two 7 mL EDTA tubes) is collected during the scheduled blood draw, without an additional visit.
Samples are transferred to the IMMEDIAB laboratory at Institut Necker Enfants Malades (Paris) for flow cytometry immunophenotyping (FACS), transcriptomic analyses and secure storage.
The participation is limited to one day-hospital visit, with no study-specific follow-up.
Outcomes and analyses :

The primary assessment compares circulating immune-cell immunophenotypic and transcriptomic profiles across liver-status strata.
The secondary analyses address inflammatory endotypes, MASLD severity, clinical/biological correlates, cardiovascular and diabetic foot risk indicators, and comparison with T2D. Analyses will include between-group comparisons, multivariable regression adjusted for relevant covariates, dimensionality reduction and differential gene-expression analyses, as specified in the protocol.
Study duration : The planned recruitment and overall study period is 24 months. The study was approved by the Comité de protection des personnes Ouest IV on October 5, 2026 (reference 26.02617.000442).

¿Quién podría participar?

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Inclusion Criteria:

Male or female subject aged \> 18 years;
Subject living with type 1 diabetes (T1D) in the study arm, with a FibroScan examination scheduled during a day hospital (DH) visit;
Subject living with type 2 diabetes (T2D) who has previously participated in the AngioSafe T2D cohort, in the control arm;
Subject who verbally agrees to participate in the study (i.e., expresses no objection), after having been informed and given a reasonable period for consideration.

Exclusion Criteria:

Subject with another chronic inflammatory disease (such as psoriasis, sarcoidosis, rheumatoid arthritis, inflammatory bowel disease, etc.);
Subject with conditions affecting the immune system (cancer, hematological malignancies, HIV);
Subject with an acute biological inflammatory syndrome (CRP \> 10 mg/L; leukocyte count \> 12 G/L) during the day hospital (DH) visit;
Subject who has expressed opposition to participation in the study or to the reuse of their data.

Población del estudio

Study arm: All consecutive adult patients living with type 1 diabetes who attend the day hospital units of the diabetology departments at Lariboisière and Bichat Hospitals (Paris) and undergo liver assessment using FibroScan as part of routine clinical care.

\- Control arm: Data from patients living with type 2 diabetes (T2D) who were previously enrolled in the AngioSafe T2D cohort.

Entiende la evaluación inicial

Tratamiento, grupos y participación

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Asignación: No informado
Enmascaramiento: No informado

Control arms

Control arms with data from patients living with type 2 diabetes (T2D) who were previously included in the AngioSafe T2D cohort.

Study arm

Study arm comprising all consecutive adult patients living with type 1 diabetes who attend the day hospital units of the diabetology departments at Lariboisière and Bichat Hospitals (Paris), during which they undergo liver assessment using FibroScan as part of routine clinical care.

Prepara tus preguntas

Qué evalúan los investigadores

Estas medidas indican qué se estudia. No prueban que un tratamiento funcione.

Medidas principales

Comparison of circulating immune-cell subset frequencies according to liver status in patients with type 1 diabetes

Plazo: Baseline (single day-hospital visit).

Frequencies of circulating immune-cell subsets, expressed as percentages of the relevant parent cell population, will be quantified by multiparameter flow cytometry. Measurements will be compared across three liver-status groups defined by FibroScan: no steatosis (CAP \< 250 dB/m and liver stiffness \< 8 kPa), MASLD without elevated liver stiffness (CAP ≥ 250 dB/m and liver stiffness \< 8 kPa), and MASLD with elevated liver stiffness (CAP ≥ 250 dB/m and liver stiffness ≥ 8 kPa).

Comparison of circulating immune-cell gene expression profiles according to liver status in patients with type 1 diabetes

Plazo: Baseline (single day-hospital visit)

Transcriptomic profiles of circulating immune cells will be assessed using gene expression analysis. Differential gene expression between liver-status groups will be evaluated using normalized gene expression measurements and statistical analyses, as specified in the study protocol.

Medidas secundarias

Identification and characterization of inflammatory endotypes in patients with type 1 diabetes

Plazo: Baseline (single day-hospital visit)

To identify and characterize distinct inflammatory endotypes in patients with type 1 diabetes based on flow cytometry (FACS) data

Association between inflammatory profiles, inflammatory endotypes, and MASLD severity

Plazo: Baseline (single day-hospital visit)

Analyze variations in inflammatory profiles across these endotypes and their association with the development of MASLD, using flow cytometry (FACS) of biological data.

FibroScan: no steatosis (CAP \< 250 dB/m and liver stiffness \< 8 kPa), MASLD without elevated liver stiffness (CAP ≥ 250 dB/m and liver stiffness \< 8 kPa), and MASLD with elevated liver stiffness (CAP ≥ 250 dB/m and liver stiffness ≥ 8 kPa).

Association between hepatic status, inflammatory endotypes, and cardiovascular risk

Plazo: day 1, (single day-hospital visit)

To investigate the association between hepatic status, as previously defined, inflammatory endotypes, and cardiovascular risk assessed using validated clinical cardiovascular risk prediction scores and the coronary artery calcium score, a marker of coronary atherosclerotic burden. Higher scores indicate greater cardiovascular risk.

Association between hepatic status, inflammatory endotypes, and diabetic foot ulcer risk