P2092 - Progression to Fragmentation During Cellular Isolation Improves Clinical Glycemic Outcomes in Patients Undergoing Islet Cell Transplantation

Steven Hadley, , Dawn Fischer, BS, Sushela Chaidarun, MD, Kerrington Smith, MD, Timothy Gardner, MD
Dartmouth-Hitchcock Medical Center, Lebanon, NH

Introduction: Islet autotransplantation (IAT) involves a complex islet isolation process in which the explanted pancreas is digested to separate islet cells from exocrine pancreatic tissue. Islet cells transition during the isolation process from being “embedded” in exocrine pancreatic tissue, to becoming “free” once separated from the exocrine tissue, to eventually becoming “fragmented” with ongoing digestion. During this transition process, it is at the subjective discretion of the isolationist when to harvest the islets; however, it is unclear if the relative percentage of “embedded”, “free” or “fragmented” islet cells affects subsequent pancreatic endocrine function. We therefore evaluated the effect of each type of islet cell on endocrine function in patients who underwent IAT.

Methods: We performed a retrospective study of 33 patients who underwent IAT at our center from 2015-2020. A database containing the patients’ demographics, procedural details, and lab results was collected and analyzed. The primary outcome was the percent change in pre-operative vs. three month post-operative c-peptide levels.

Results: There was a weak correlation between the percent change in C-peptide and number of “fragments” (R²=0.0156) and percent of islet cells ‘embedded” (R²=0.0011). However, as the number of “fragments” increased and percent “embedded” decreased, the percent change in C-peptide approached zero. Patients older than 60 years demonstrated worse glycemic control than those younger than 60 (-77% change in C-peptide vs. -4% change in C-peptide, p=0.012). Females experienced significantly lower percent decreases in C-peptide compared to males (12% vs. 62%, p=0.037). Genetic etiologies (CFTR, SPINK1, PRSS1, CTCR, and CPA1) resulted in lower percent decreases in C-peptide than non-genetic etiologies (9% vs. 52%, p=0.152)l although this trend did not reach statistical significance. There was a trend of patients with CT scans displaying evidence of CP having a greater percent decreases in C-peptide than those with CTs lacking such evidence that did not reach significance (50% vs. 3%, p=0.149).

Discussion: Although a weak correlation existed between the number of “fragments” and the percent change in c-peptide, the data support erring on the side of allowing the digestion to proceed to more “fragments” and fewer “embedded” islets in order to enhance glycemic outcomes. As expected, younger, healthier patients without CP seen on cross-sectional imaging had the best subsequent glycemic control.


Disclosures:


Steven Hadley, , Dawn Fischer, BS, Sushela Chaidarun, MD, Kerrington Smith, MD, Timothy Gardner, MD. P2092 - Progression to Fragmentation During Cellular Isolation Improves Clinical Glycemic Outcomes in Patients Undergoing Islet Cell Transplantation, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.