Islet transplantation for brittle type 1 diabetes: the UIC protocol

Area of Science:

• Endocrinology
• Transplantation Immunology

Background:

• Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insulin deficiency.
• Allogeneic islet transplantation (Tx) offers a potential cure but requires effective immunosuppression and sufficient islet mass.
• Achieving insulin independence with reduced islet mass is a key goal in T1DM Tx.

Purpose of the Study:

• To evaluate the safety and reproducibility of allogeneic islet Tx in T1DM patients.
• To test a strategy for achieving insulin independence with lower islet mass.
• To assess the efficacy of a novel immunosuppression and treatment protocol.

Main Methods:

• Prospective phase 1/2 trial involving ten C-peptide negative T1DM subjects with hypoglycemic unawareness.
• Subjects received 1-3 intraportal allogeneic islet Tx over 15 months.
• Group 1 (n=4) received Edmonton immunosuppression; Group 2 (n=6) received Edmonton regimen plus etanercept and exenatide.

Main Results:

• All subjects achieved insulin independence.
• Group 2 required significantly fewer islets (537,495 +/- 190,968 EIN) for insulin independence after one Tx compared to Group 1 (1,460,080 +/- 418,330 EIN).
• Both groups achieved normal HbA1c levels; Group 2 demonstrated improved islet graft function with the combined treatment.

Conclusions:

• Allogeneic islet transplantation is safe and reproducible in T1DM patients.
• The combination of etanercept and exenatide with standard immunosuppression facilitates insulin independence with reduced islet mass.
• This strategy improves islet graft function and offers a promising approach for T1DM management.