M Kizilgul1, J J Wilhelm2, T B Dunn3, G J Beilman3, T L Pruett3, S Chinnakotla3, K Amin4, B J Hering2, M D Bellin5. 1. Department of Endocrinology and Metabolism, SBU Diskapi Training and Research Hospital, Ankara, Turkey; Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA. Electronic address: mkizilgu@umn.edu. 2. Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA. 3. Department of Surgery, University of Minnesota, Minneapolis, MN, USA. 4. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA. 5. Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Abstract
AIM: Islet autotransplantation (IAT) is considered a 'non-immune' model of islet transplant, with no risk for autoimmune-mediated beta cell loss, but we have previously observed de novo type 1 diabetes in one total pancreatectomy with islet autotransplantation (TPIAT) recipient. We aimed to investigate the clinical significance of glutamic acid decarboxylase antibodies (GADA), as a sensitive marker for autoimmune diabetes mellitus (DM), in patients with chronic pancreatitis undergoing TPIAT. METHODS: We identified 9 patients undergoing TPIAT with elevated GADA pre-TPIAT (8 non-diabetic and 1 with C-peptide positive DM), otherwise demographically similar to GADA negative TPIAT recipients (n=341). Metabolic and clinical measures related to islet cell function were recorded both before and after TPIAT. RESULTS: None of the 9 TPIAT patients achieved insulin independence after surgery, vs. 33% of GADA negative patients (n=318 with 1-yr follow-up). The two patients with the highest titters of GADA (>250 IU/mL) both experienced islet graft failure, despite normoglycaemia pre-TPIAT and high islet mass transplanted (5276 and 9378 IEQ per kg), with elevated HbA1c levels post-TPIAT (8.3%, 9.6%). The remaining 7 seven were insulin dependent with partial graft function and HbA1c levels <7%. CONCLUSION: Insulin dependence was more frequent in 9 patients with elevated GADA prior to TPIAT than in GADA negative TPIAT recipients, with graft failure in 2 cases. We speculate that beta-cell autoimmunity may occur in a small subset of TPIAT recipients and that beta cell antibody testing prior to TPIAT may be warranted to identify individuals at higher risk for insulin dependence.
AIM: Islet autotransplantation (IAT) is considered a 'non-immune' model of islet transplant, with no risk for autoimmune-mediated beta cell loss, but we have previously observed de novo type 1 diabetes in one total pancreatectomy with islet autotransplantation (TPIAT) recipient. We aimed to investigate the clinical significance of glutamic acid decarboxylase antibodies (GADA), as a sensitive marker for autoimmune diabetes mellitus (DM), in patients with chronic pancreatitis undergoing TPIAT. METHODS: We identified 9 patients undergoing TPIAT with elevated GADA pre-TPIAT (8 non-diabetic and 1 with C-peptide positive DM), otherwise demographically similar to GADA negative TPIAT recipients (n=341). Metabolic and clinical measures related to islet cell function were recorded both before and after TPIAT. RESULTS: None of the 9 TPIAT patients achieved insulin independence after surgery, vs. 33% of GADA negative patients (n=318 with 1-yr follow-up). The two patients with the highest titters of GADA (>250 IU/mL) both experienced islet graft failure, despite normoglycaemia pre-TPIAT and high islet mass transplanted (5276 and 9378 IEQ per kg), with elevated HbA1c levels post-TPIAT (8.3%, 9.6%). The remaining 7 seven were insulin dependent with partial graft function and HbA1c levels <7%. CONCLUSION:Insulin dependence was more frequent in 9 patients with elevated GADA prior to TPIAT than in GADA negative TPIAT recipients, with graft failure in 2 cases. We speculate that beta-cell autoimmunity may occur in a small subset of TPIAT recipients and that beta cell antibody testing prior to TPIAT may be warranted to identify individuals at higher risk for insulin dependence.
Authors: Kyu Shik Mun; Jaimie D Nathan; Tom K Lin; Deborah A Elder; Anil G Jegga; Anjaparavanda P Naren; Maisam Abu-El-Haija Journal: Pancreas Date: 2022-04-01 Impact factor: 3.243
Authors: Anna Casu; Paul J Grippo; Clive Wasserfall; Zhaoli Sun; Peter S Linsley; Jessica A Hamerman; Brian T Fife; Adam Lacy-Hulbert; Frederico G S Toledo; Phil A Hart; Georgios I Papachristou; Melena D Bellin; Dhiraj Yadav; Maren R Laughlin; Mark O Goodarzi; Cate Speake Journal: Pancreas Date: 2022-07-01 Impact factor: 3.243
Authors: Melena D Bellin; Mark Lowe; M Bridget Zimmerman; Michael Wilschanski; Steven Werlin; David M Troendle; Uzma Shah; Sarah J Schwarzenberg; John F Pohl; Emily Perito; Chee Yee Ooi; Jaimie D Nathan; Veronique D Morinville; Brian A McFerron; Maria R Mascarenhas; Asim Maqbool; Quin Liu; Tom K Lin; Sohail Z Husain; Ryan Himes; Melvin B Heyman; Tanja Gonska; Matthew J Giefer; Cheryl E Gariepy; Steven D Freedman; Douglas S Fishman; Bradley Barth; Maisam Abu-El-Haija; Aliye Uc Journal: J Pediatr Gastroenterol Nutr Date: 2019-11 Impact factor: 2.839
Authors: Khawla F Ali; Vicente T San Martin; Tyler Stevens; R Matthew Walsh; Rita Bottino; Massimo Trucco; Betul Hatipoglu Journal: OBM Transplant Date: 2018-07-03