237-OR: Gastrin Improves Single Islet Transplant Outcomes

• Published in: Diabetes (New York, N.Y.) Vol. 72; no. Supplement_1; p. 1
• Main Authors: HACKER-STRATTON, JEANNETTE, ORR, CHRIS, OMORI, KEIKO, QI, MEIRIGENG, FOROUHAR, ELENA, EL-SHAHAWY, MOHAMED, KANDEEL, FOUAD R.
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 20.06.2023
• Subjects: Allografts; Angiogenesis; Clinical trials; Etanercept; Fetuses; Gastrin; Immunosuppression; Inflammation; Insulin; Interleukin 1 receptor antagonist; Lymphocytes T; Monoclonal antibodies; Pancreas; Pancreatic islet transplantation; Thymoglobulin; Transplants & implants
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db23-237-OR

Background: Multiple allogenic islet transplants (ITs) are usually required to supply adequate islet mass (~10,000 IEQ/kg) to induce insulin independence. Improving outcomes of a SINGLE islet transplant are needed. Gastrin is a gut hormone that is involved in normal fetal pancreas development. Evidence by our group and others have shown gastrin can support islet cell expansion/function and have anti-inflammatory and pro-angiogenesis effects. We compared outcomes of IT alone across 3 clinical trials using: Edmonton-based (ITA), T-cell depleting (TCD), and TCD immunosuppression with an investigational gastrin analogue (GAS). Methods: Between 2004-2022, a total of 31 evaluable T1D patients without a prior history of transplant received IT-alone under the ITA (n=17), TCD (n=7), and GAS (n=7) clinical trials. Participants in ITA and TCD were eligible to receive up to 3 ITs each. GAS participants received only a single IT and two 30-day courses of gastrin (SQ, BID) at the time of IT and again 6 months later. Immunosuppression included basiliximab or daclizumab + etanercept (ITA) and T-cell depletion (anti-thymoglobulin) + etanercept + anakinra (TCD and GAS). Results: Progressive improvements in engraftment were observed in the ITA, TCD, and GAS trials. Average insulin requirements were reduced by 18, 26, and 33 u/day. GAS subjects showed the most rapid reduction of 30.9 u/day (94%) in the first 2 weeks post-IT, compared to 17.5 u/day (67%) in TCD. Rates of subjects achieving insulin independence with a SINGLE islet transplant were 0, 15, and 57%. Subjects required an average of 3 ITs in ITA, 2 in TCD, and only one IT in GAS to achieve insulin independence. Average numbers of islets required to achieve insulin independence were 13,280, 8,433 and 4,837 IEQ/kg. Conclusion: Gastrin use in the peri-transplant period leads to rapid engraftment, larger magnitude of insulin reduction, and permitted achievement of insulin independence in more than half of subjects after a single islet transplant of less than half the normally targeted islet dose.