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

2026年11月3日 更新者：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.

研究概览

地位

尚未招聘

条件

详细说明

  • 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).

研究类型

观察性的

注册 (估计的)

1000

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 法国
      • Paris、法国、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
        • 接触：
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

取样方法

非概率样本

研究人群

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.

描述

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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 观测模型：COHORT
  • 时间观点：PROSPECTIVE

队列和干预

团体/队列
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.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Comparison of circulating immune-cell subset frequencies according to liver status in patients with type 1 diabetes
大体时间：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
大体时间：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)

次要结果测量

结果测量
措施说明
大体时间
Identification and characterization of inflammatory endotypes in patients with type 1 diabetes
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Assistance Publique - Hôpitaux de Paris

合作者

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

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

  • 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.,

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年12月1日

初级完成 (估计的)

2028年12月31日

研究完成 (估计的)

2028年12月31日

研究注册日期

首次提交

2026年10月23日

首先提交符合 QC 标准的

2026年11月3日

首次发布 (实际的)

2026年11月10日

研究记录更新

最后更新发布 (实际的)

2026年11月10日

上次提交的符合 QC 标准的更新

2026年11月3日

最后验证

2026年11月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • APHP 260861

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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