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Immunological Signatures of MASLD and MASH in Patients With Type 1 Diabetes (SMASH-IMM1)

3 de novembro de 2026 atualizado por: Assistance Publique - Hôpitaux de Paris

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.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Descrição detalhada

  • 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).

Tipo de estudo

Observacional

Inscrição (Estimado)

1000

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

  • França
      • Paris, França, 75010
        • Hospital, AP-HP, 2 rue Ambroise Paré, Paris, France (coordinating center) - Department of Diabetology, Bichat Hospital, AP-HP, 46 Rue Henri Huchard, Paris, France
        • Contato:
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Método de amostragem

Amostra Não Probabilística

População do estudo

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.

Descrição

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.

Plano de estudo

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Como o estudo é projetado?

Detalhes do projeto

  • Modelos de observação: COHORT
  • Perspectivas de Tempo: PROSPECTIVE

Coortes e Intervenções

Grupo / Coorte
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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Comparison of circulating immune-cell subset frequencies according to liver status in patients with type 1 diabetes
Prazo: 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).
Baseline (single day-hospital visit).
Comparison of circulating immune-cell gene expression profiles according to liver status in patients with type 1 diabetes
Prazo: 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.
Baseline (single day-hospital visit)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Identification and characterization of inflammatory endotypes in patients with type 1 diabetes
Prazo: Baseline (single day-hospital visit)

To identify and characterize distinct inflammatory endotypes in patients with type 1 diabetes based on flow cytometry (FACS) data
Baseline (single day-hospital visit)
Association between inflammatory profiles, inflammatory endotypes, and MASLD severity
Prazo: 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).
Baseline (single day-hospital visit)
Association between hepatic status, inflammatory endotypes, and cardiovascular risk
Prazo: 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.
day 1, (single day-hospital visit)
Association between hepatic status, inflammatory endotypes, and diabetic foot ulcer risk
Prazo: Day 1, (single day-hospital visit)

To investigate the association between hepatic status, as previously defined, inflammatory endotypes, and diabetic foot ulcer risk, assessed using standard clinical grading systems incorporating peripheral neuropathy, lower limb peripheral arterial disease, foot deformities, and history of previous ulcers or amputations.
Day 1, (single day-hospital visit)
Comparison of inflammatory signatures between type 1 and type 2 diabetes
Prazo: Day 1, (single day-hospital visit)

To compare inflammatory signatures associated with MASLD/MASH in patients with type 1 diabetes with those observed in patients with type 2 diabetes, using data from the existing AngioSafe T2D cohort.
Day 1, (single day-hospital visit)
Prevalence of MASLD and MASH in patients with type 1 diabetes
Prazo: Day 1, (single day-hospital visit)

To estimate the prevalence of MASLD and MASH among patients with type 1 diabetes in the study population.
Day 1, (single day-hospital visit)
Risk factors associated with MASLD and MASH in patients with type 1 diabetes
Prazo: Day 1, (single day-hospital visit)

To identify clinical, biological, and metabolic risk factors associated with the development of MASLD and MASH in patients with type 1 diabetes.
Day 1, (single day-hospital visit)
Clinical and demographic characteristics of patients with type 1 diabetes according to hepatic status
Prazo: Day 1, (single day-hospital visit)

To describe the clinical and demographic characteristics of patients with type 1 diabetes according to their hepatic status, assessed by FibroScan, using the following categories:

  • 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.
  • MASLD with elevated liver stiffness: CAP ≥ 250 dB/m and liver stiffness ≥ 8 kPa.
Day 1, (single day-hospital visit)

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Assistance Publique - Hôpitaux de Paris

Colaboradores

Laboratoire IMMEDIAB - Institut Necker Enfants Malades (INEM), Paris

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

  • Ancel , P., Martin, J., Doukbi , E., Houssays, M., Gascon, P., Righini, M., . . . Gaborit , B. (2023). Untargeted Multiomics Approach Coupling Lipidomics and Metabolomics Profiling Reveals New Insights in Diabetic Retinopathy. Int J Mol Sci, 24(15), 12053. doi:10.3390/ijms241512053 De Vries , M., Westerink, J., H A H Kaasjager, K., & W de Valk, H. (2020). Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Patients With Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Clin Endocrinol Metab, 105(12), 3842-3853. doi:10.1210/clinem/dgaa575 De Vries, M., Westerink, J., H.A.H Kaasjager, K., & W. de Valk, H. (2020). Prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with surrogate markers of insulin resistance in patients with type 1 diabetes. The Journal of Clinical Endocrinology & Metabolism, 105(12), 3842-3853. doi:10.1016/j.diabres.2022.109827 European Association for the Study of the Liver, (., European Association for the Study of Diabetes, (., & European Association for the Study of Obesity, (. (2024). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol, 81(3), 492-542. doi:10.1016/j.jhep.2024.04.031 Gaborit, B., Julla , J.-B., Besbes, S., Proust , M., Vincentelli, C., Alos, B., . . . Germain, S. (2020). Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study. J Clin Endocrinol Metab, 105(4), dgz069. doi:10.1210/clinem/dgz069 Goto , H., & Takamura, T. (2025). Metabolic Dysfunction-Associated Steatotic Liver Disease Complicated by Diabetes: Pathophysiology and Emerging Therapies. J Obes Metab Syndr, 34(3), 224-238. doi:10.7570/jomes25017 M Younossi, Z., Kalligeros, M., & Henry, L. (2024). Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol, 31(Suppl), S32-S50. doi:10.3350/cmh.2024.0431 Mertens , J., Weyler, J., Dirinck, E.,

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de dezembro de 2026

Conclusão Primária (Estimado)

31 de dezembro de 2028

Conclusão do estudo (Estimado)

31 de dezembro de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

23 de outubro de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

3 de novembro de 2026

Primeira postagem (Real)

10 de novembro de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

10 de novembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

3 de novembro de 2026

Última verificação

1 de novembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • APHP 260861

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