Targeting GLUT1 to Control Autoimmunity in Type 1 Diabetes (GLUT1D)
Type 1 Diabetes is an autoimmune disease in which immune cells contribute to the destruction of insulin-producing pancreatic beta cells. This study investigates whether targeting glucose transporter 1 (GLUT1), a transporter involved in immune cell metabolism, may help modulate autoimmune responses associated with Type 1 Diabetes.
The study uses previously collected and biobanked peripheral blood mononuclear cells (PBMCs) from individuals with Type 1 Diabetes. No additional visits, blood draws, or study-specific procedures will be performed on human participants.
Study Overview
Status
Conditions
Detailed Description
Type 1 Diabetes is an autoimmune disease characterized by immune-mediated destruction of pancreatic beta cells. Autoreactive T cells play a central role in this process and may persist over time within the memory T-cell compartment. Understanding the mechanisms that sustain autoreactive T-cell activation, survival, proliferation, and inflammatory function is therefore important for the development of more targeted immune-modulatory strategies.
Activated T cells undergo metabolic reprogramming to support their functional responses. In this context, glucose uptake and glycolytic metabolism are important components of T-cell activation. GLUT1 is a key glucose transporter involved in this metabolic adaptation and may contribute to the ability of autoreactive T cells to expand and maintain effector functions.
This study will use previously collected and biobanked peripheral blood mononuclear cell (PBMC) samples from individuals with Type 1 Diabetes. The PBMC samples will be retrieved in coded form, thawed, and infused into immunodeficient NOD scid gamma (NSG) mice to reconstitute a human immune system and generate humanized preclinical models. These models will be used to investigate the phenotype, activation state, metabolic profile, inflammatory function, and transcriptional features of human immune cells in relation to GLUT1 modulation. Experimental approaches include flow cytometry-based immunophenotyping, cytokine assessment, and transcriptomic analyses performed on human immune cells recovered from the humanized mice.
The study is observational and retrospective with respect to human participants. All human biological material and associated data were collected before the start of this study and are stored in coded or pseudonymized form. The study does not involve prospective enrollment of human participants, administration of an investigational product to human participants, additional biological sampling, clinical visits, or other study-specific procedures involving human participants.
The purpose of the study is to generate mechanistic and translational evidence on the role of GLUT1-dependent immune metabolism in Type 1 Diabetes-associated autoimmunity, using humanized preclinical models generated from biobanked PBMC samples. The study is intended to support the future development of targeted strategies aimed at modulating pathogenic autoreactive immune responses.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Carla Di Dedda, PhD
- Phone Number: +39 0226434369
- Email: didedda.carla@hsr.it
Study Contact Backup
- Name: Lorenzo Piemonti, MD
- Phone Number: +39 0226432706
- Email: piemonti.lorenzo@hsr.it
Study Locations
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Milan, Italy, 20132
- IRCCS San Raffaele Scientific Institute
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Contact:
- Lorenzo Piemonti, MD
- Phone Number: +39 0226432706
- Email: piemonti.lorenzo@hsr.it
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Contact:
- Carla Di Dedda, PhD
- Phone Number: +39 02 26434369
- Email: didedda.carla@hsr.it
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Principal Investigator:
- Carla Di Dedda, PhD
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Sub-Investigator:
- Lorenzo Piemonti, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- PBMC samples obtained from adult subjects aged 18 years or older at the time of sample collection.
- Documented diagnosis of Type 1 Diabetes.
- PBMC samples already collected and stored in the institutional Biobank of IRCCS Ospedale San Raffaele.
- PBMC samples obtained from subjects who had previously provided written informed consent for the collection, storage, and research use of biological material and associated data.
Exclusion Criteria:
- PBMC samples obtained from subjects younger than 18 years at the time of sample collection.
- Presence of relevant concomitant diseases or clinical conditions that, in the Investigator's judgment and based on available records, may interfere with the interpretation of immunological analyses or with the study objectives.
- Insufficient sample availability, inadequate sample quality, or missing essential sample-related information preventing use of the PBMC sample for the planned research activities.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Adults With Type 1 Diabetes
Previously collected PBMC samples obtained from adult subjects with a documented diagnosis of Type 1 Diabetes and stored at the institutional Biobank of IRCCS Ospedale San Raffaele.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Human Immune Cell Engraftment/Reconstitution
Time Frame: 28 days after peripheral blood mononuclear cells (PBMCs) infusion
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Successful human immune cell engraftment/reconstitution will be assessed by detection and quantification of human CD45-positive cells and relevant immune cell subsets in peripheral blood and lymphoid tissues of recipient NOD scid gamma (NSG) mice.
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28 days after peripheral blood mononuclear cells (PBMCs) infusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Quantitative and Phenotypic Profile of Human Immune Cell Subsets
Time Frame: 28, 44, and 58 days after PBMC infusion
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Human immune cell subsets will be quantitatively and phenotypically analyzed after in vivo reconstitution in recipient NSG mice.
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28, 44, and 58 days after PBMC infusion
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Carla Di Dedda, PhD, IRCCS San Raffaele
- Study Chair: Lorenzo Piemonti, MD, IRCCS San Raffaele
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SG-2024-12380508 (GLUT1D)
- SG-2024-12380508 (Other Identifier: Italian Ministry of Health)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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