*Purpose: Islet identity loss is an emergent factor in dysglycemia in diabetes, islet transplantation, and chronic pancreatitis (CP). Pancreatectomy and islet auto-transplantation (PIAT) for CP treatment is a useful model for assessing islet function in the absence of immune-suppression and to perform extensive pre-surgical metabolic testing not possible in cadaveric-sourced donor. We recently showed that in CP-PIAT patients, pre-surgical elevations in insulin resistance metrics proinsulin and HOMA-IR were associated with poorer post-surgical glycemic outcomes (insulin dependence) as well as histological islet identity loss. Here we sought to examine other measures of pre-surgical islet function and estimates of PIAT success using HOMA-β and insulin independence equations in a larger auto-transplant patient cohort.

*Methods: Seven PIAT patients were assessed for β-cell function metrics, including pre- and 6-month-post-transplant HOMA-β by fasting insulin and glucose, comparison to the SUITO index using C-peptide, and proposed insulin independence by the BETA-2 score. Pancreas histology at PIAT was examined for changes in cellular maturity markers and compared with non-diabetic and T2DM donor controls.

*Results: Pre-PIAT, low-HOMA-β was largely predictive of post-PIAT insulin dependence. Pre- and post-PIAT HOMA-β-CP values closely aligned with the SUITO equation, and there was a general correlation between BETA-2 score post-PIAT relative to the predicted index threshold for insulin independence. Histological data supported serological estimates of β-cell function, showing that poor HOMA-β pre-transplant corresponded with increased insulin-glucagon and insulin-vimentin colocalization, and reductions in Ins/Syp ratio, UCN3 presence, and overall islet area.

*Conclusions: These data encourage further examination of islet identity peri-transplant and the association with pre-surgical serological β-cell function, as well as the use of PIAT for studying β-cell phenotype and its functional clinical implications.

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