Abstract
Disclosure: A. Olayiwola: None. F. Vendrame: None. D. Baidal: None. G. Burke: None. A. Pugliese: None. R. Varghese: None. Introduction: Pancreas transplantation is a well-established treatment for patients with Type 1 Diabetes Mellitus (T1DM), especially those with end-stage renal disease (ESRD). However, type 1 diabetes recurrence (T1DR) after transplantation can lead to graft dysfunction and a return to insulin dependence. Case report: A 50-year-old female with a history of T1DM, complicated by diabetic retinopathy, neuropathy, and nephropathy progressing to ESRD, underwent a simultaneous pancreas-kidney transplant with immediate graft function. Eight years after transplantation, she presented with a three-week history of polyuria, polydipsia, and fatigue. Laboratory data were significant for glucose 364 mg/dL, A1c 12.4%, C-peptide 0.94 ng/mL, beta-hydroxybutyrate 1.02 mmol/L (reference: 0.02-0.27 mmol/L). Electrolytes were notable for sodium 131 mEq/L (corrected: 135 mEq/L), potassium 4.9 mEq/L, HCO3- 20mmol/L (22-30mmol/L), chloride 97 mEq/L, CO₂ 25 mEq/L, and an anion gap of 9 (reference 7-15). Urinalysis revealed >1000 mg/dL glucose, 70 mg/dL protein, and 10 ketones. Renal function showed a creatinine of 1.00 mg/dL and an eGFR of 69 mL/min, stable from prior values. Pancreatic enzymes were within normal limits: serum amylase 33 U/L and lipase 44 U/L. Liver function tests were also within normal range: ALT 14 U/L, AST 24 U/L, ALP 102 U/L, and total bilirubin 0.6 mg/dL. Follow-up antibody testing revealed an elevated Glutamic Acid Decarboxylase 65 antibody (anti-GAD65) at 7 IU/mL (reference: <5 IU/mL), with normal insulin autoantibody (<0.4 U/mL), IA-2 antibody (<5.4 U/mL), and Zinc Transporter 8 antibody (ZnT8) (<10 U/mL). Ultrasound duplex imaging of the transplanted kidneys showed patent renal vessels with normal resistive indices. Despite initial treatment with immunosuppressive steroids for suspected pancreas rejection, the pancreatic graft failed to restore euglycemia, necessitating re-initiation of insulin therapy. Overall, the clinical findings and biomarker profile suggested possible T1DR, a rare but recognized complication in pancreas transplant recipients. Conclusion: T1DR involves the reactivation of autoimmune processes that target the transplanted pancreas, similar to the destruction of native beta cells. It is typically identified by diabetes ketoacidosis in association with rising HbA1c, decreasing C-peptide, renewed insulin dependence, and positive autoantibodies. For these patients, re-transplantation is currently a possible therapeutic option, but is not curative, since T1DR typically recurs in the re-transplanted pancreas as well. Further studies are needed to improve understanding of the immunologic mechanisms behind T1DR and to optimize strategies for managing these patients. Presentation: Sunday, July 13, 2025