Allogeneic Regenerative Islet Transplantation for the Treatment of Brittle Type 1 Diabetes Mellitus

Inclusion criteria

• Age 6-65 years, gender not specified.
• Despite intensified exogenous insulin therapy, blood glucose control remains inadequate [glycated hemoglobin ≥7.5%, or TIR (time in range) <70%].
• Able and willing to use the blood glucose meter provided by the sponsor, conduct self-blood glucose monitoring as required, and complete the patient log as instructed.
• Fertile eligible subjects (male or female) must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence) during the trial and for at least 90 days after the last dose; premenopausal female patients must have a negative pregnancy test before enrollment.
• Diagnosed with type 1 diabetes for at least 1 year based on the World Health Organization (WHO) disease diagnostic criteria, and at least one positive result for diabetes-related autoantibodies [glutamic acid decarboxylase autoantibody (GADA), insulinoma-associated-2 autoantibody (IA-2A), insulin autoantibody (IAA), islet cell antibody (ICA), zinc transporter 8 antibody (ZaT8A)]. Experiencing two or more severe hypoglycemic events in the past year, with at least one severe hypoglycemic event in the past 3 months (severe hypoglycemia defined as blood glucose below 2.9 mmol/L or inability to self-correct during hypoglycemia).
• Voluntarily participate and sign the informed consent form.

Exclusion criteria

• Uncontrolled systemic infections, including but not limited to pulmonary tuberculosis, active hepatitis, a history of positive human immunodeficiency virus (HIV) testing, and positive syphilis treponemal antibody (TP);
• Presence of significant organic lesions in vital organs such as the heart, lungs, or brain;
• Complications of severe diabetes, including but not limited to retinal hemorrhage, diabetic foot, etc.;
• Liver function tests with total bilirubin, ALT, and AST ≥2×ULN, and failure to normalize after drug treatment;
• Untreated cancer or less than 1 year since cure;
• Severe gastrointestinal dysfunction, gastrointestinal immune diseases, and inability to take immunosuppressant;
• History of smoking, alcohol abuse, or drug misuse;
• Severe mental or psychological disorders;
• Various advanced metabolic diseases (such as hyperuricemia, etc.);
• Participation in other clinical trials in the 3 months prior to enrollment;
• Patients requiring long-term oral/intravenous administration of high-dose glucocorticoids due to various diseases;
• Pregnant or lactating women;
• Investigator judgment indicating clear evidence of severe, active, uncontrolled endocrine or autoimmune abnormalities other than type 1 diabetes;
• Other situations judged by the investigator as unsuitable for participation in the trial.