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

* 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).