Introduction. Pancreatic islet transplantation is an established therapeutic option for subjects with type 1 diabetes who have hypoglycemia unawareness syndrome and frequent problematic hypoglycemic episodes when other methods comprising diabetes education and use of technological support fail. Because the current standard method of islet infusion into the liver has some limitations, novel approaches are under investigation.  Recently, a technique for islet placement into the momentum was developed at the Diabetes Research Institute in Miami.

Methods. Inspired by the Miami protocol we first tested in experiment preparation of a biocompatible thrombin-plasma gel using the human thrombin component of the Surgiflo (Ethicon) hemostatic matrix set.  Thrombin was reconstituted in aqua pro injection and transferred to a separate syringe.Here we report our first results with two cases of islet transplantation into an omental pouch using a biocompatible plasma-fibrin gel (ClinicalTrials.gov (NCT04884633).  The recipients, a 43 years old woman and a 66 years old man suffered from life-threatening forms of hypoglycemia unawareness despite using continuous glucose monitoring and insulin pumps in a low-suspend mode. The mail recipient had previously undergone two islet transplants into the liver with completely failed function. His second implantation was complicated by serious bleeding and an additional intraportal procedure was contraindicated.The recipients received 12,350 and 3813 islet equivalents per kilogram that were mixed with autologous plasma. The islets were implanted during a laparoscopic procedure on the surface of omentum, overlaid with human thrombin solution, and fixed by flapping the omentum over.

Results: During a 9-month follow-up, neither patient experienced any moderate or severe hypoglycemia. Their glucose profiles significantly improved, insulin dose decreased by approximately 50%, and C-peptide at 1 year was 0.22 and 0.14 pmol/ml, respectively. HbA1c levels at 1 year wer 48 and 52 mmol/mol. The postoperative course was free of serious adverse events. However, C-peptide production in the first patient progressively declined at 1 year and hypoglycemic episodes recurred.

Discussion: Though the results for these first two cases are not satisfactory, we have demonstrated the feasibility, safety, and ability of this novel technique to restore insulin production and prevent hypoglycemic episodes. Further refinements to improve immediate islet survival are necessary. Our immediate modifications should include shortening the procedural time and better selection of the omental surface according to vascular supply as observed by laparoscopy.