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Beta cell death may occur both after islet isolation and during infusion back into recipients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis. We measured the novel beta cell death marker unmethylated insulin (INS) DNA in TPIAT recipients before and immediately after islet infusion (n=21), and again 90 days post-TPIAT concurrent with metabolic functional assessments (n=25). As expected, INS DNA decreased after pancreatectomy (p=0.0002). Following islet infusion, all TPIAT recipients had an elevated unmethylated INS DNA ratio in the first hours. In 4 samples (3 patients), INS DNA was also assessed immediately after islet isolation and again before islet infusion to assess the impact of the isolation process: unmethylated and methylated INS DNA fractions both increased over this interval, suggesting death of beta cells and exocrine tissue before islet infusion. Higher mixed meal testing glucose excursion was associated with persistently elevated INS DNA at day 90. In conclusion, we observed universal early elevations in the beta cell death marker INS DNA after TPAIT, with pronounced elevations in the islet supernatant pre-infusion, likely reflecting beta cell death induced by islet isolation. Persistent post-transplant elevation of INS DNA predicted greater hyperglycemia at 90 days.

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