Introduction and Objective: One-third of chronic pancreatitis (CP) patients who undergo total pancreatectomy with islet autotransplantation (TPIAT) achieve insulin independence. Little is known regarding diabetes (DM) related genetics on TPIAT. Genetic risk scores (GRS) are utilized in type 1 (T1D) and type 2 (T2D) DM to predict C-peptide (Cpep) before diagnosis.Methods: We genotyped 384 patients with CP who underwent TPIAT enrolled in the multicenter “POST” study using the Global Screening Array to assess the influence of T1D and T2D GRS and 14 pre-specified SNPs associated with Cpep preservation on 1 year TPIAT outcomes.Results: Patients were 30 ± 17 years, 62% female, 92% Caucasian, 13% previously had DM and received 4294 ± 3458 IEQ/kg during TPIAT. One year post TPIAT 80% required insulin, fasting Cpep was 0.98 ± 0.79 ng/mL and insulin dose adjusted A1c (IDAA1C) was 8.4 ± 2.8. Having diabetes before TPIAT was associated with higher T1D GRS1 (mean Z-score 0.27 ± 0.8 vs -0.04 ± 1.0 in non-DM, p=0.03) and higher T2D GRS (mean Z-score 0.52 ± 1.2 vs -0.07 ± 1.0, p=0.003). At 1 year after TPIAT higher T2D GRS was associated with a lower fasting Cpep (β=-0.09 per 1 SD, p=0.04) and higher IDAA1C (β=0.45 per 1 SD, p=0.009). Several pre-selected SNPs had a trend of lower mean fasting Cpep 1 year post TPIAT (Table).Conclusion: Genetic risk factors for T1D and T2D may impact the risk for DM in CP and insulin secretion after TPIAT.
T.M. Triolo: None. A. Eaton: None. W. Chen: None. S. Onengut-Gumuscu: None. A. Steck: Advisory Panel; Sanofi-Aventis U.S. M. Bellin: Advisory Panel; Vertex Pharmaceuticals Incorporated. Research Support; ViaCyte, Inc. Advisory Panel; Novo Nordisk. Consultant; Soleno. Research Support; Dexcom, Inc. Advisory Panel; bridgebio.
NIDDK (K23 DK136931)
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