1141-OR: Amylin Secretory Ratio as a Marker of β-Cell Stress in Type 1 Diabetes Islet Transplant Recipients

Introduction and Objective: Type 1 diabetes (T1D) requires lifelong insulin therapy and glucose monitoring, creating a substantial disease burden. Allogeneic islet transplantation improves glycemic control but graft decline over time is a limitation. Amylin (a.k.a. islet amyloid polypeptide), co-secreted from the β-cell with insulin, may be disproportionately released in times of β-cell stress. The objective of this study is to determine whether the amylin/C-peptide ratio predicts islet graft decline in T1D islet transplant recipients. Methods: This longitudinal cohort study included eleven individuals with T1D who received islet transplantation between 2008-2012. Patients underwent repeat glucose potentiated arginine testing at 2.5 months post-transplant and annually for up to 7 years, with measurement of insulin, C-peptide, amylin, and proinsulin concentrations. The primary outcome was the β-cell secretory capacity assessed by the glucose potentiated acute C-peptide response (ACRpot), and proinsulin secretory ratios which were used as a previously validated measure of β-cell stress. Amylin/C-peptide secretory ratios were compared against measures of β-cell graft function and stress using partial correlation coefficient analysis. Results: Across the cohort, acute insulin and C-peptide responses declined over time, reaching their lowest values at 72 months post-transplant, while amylin secretion progressively increased. Consequently, amylin/C-peptide ratios rose over time post-transplant. The increase in amylin/C-peptide ratios over time were inversely related to the decrease in ACRpot (ICC = -0.344; P < 0.01). The increase in amylin/C-peptide ratios were also related to increasing proinsulin secretory ratios over time (ICC = 0.3473; P = 0.01). Conclusion: Increasing amylin/C-peptide ratios are significantly associated with declining β-cell secretory capacity following islet transplantation. This measure may serve as a clinically useful marker of islet β-cell graft stress, potentially informing timing of re-transplantation. Disclosure A. Parikh: None. A. Flatt: Employee; Ended; Vertex Pharmaceuticals Incorporated. A.M. Matus: None. M.R. Rickels: Consultant; Ended; Novo Nordisk. Consultant; Current; Vertex Pharmaceuticals Incorporated. Other - Invited speaker; Ended; Bayer AG. Consultant; Current; Sernova, Corp., Sanofi. Research Support; Current; Dompé, vTv Therapeutics, Hua Medicine. Research Support; Ended; Tandem Diabetes Care, Inc.