Hypoglycemia Occurrence and Risk Factors in Insulin Independent Patients After Total Pancreatectomy With Islet Autotransplantation

Background: Total pancreatectomy with islet auto-transplantation (TPIAT) alleviates pain and preserves islet function in patients with severe pancreatitis. Although approximately one third of recipients achieve insulin independence, spontaneous hypoglycemia has been observed in this population. Its frequency, risk factors, and management remain poorly characterized. Methods: Using prospectively collected data on insulin-independent (TPIAT) recipients at the University of Minnesota (2010–2023), we compared patients who developed hypoglycemia (defined as documented blood glucose < 70 mg/dL) to those with no reported hypoglycemia. Demographic, clinical, surgical, and metabolic variables were evaluated, and treatment strategies were reviewed. Results: Among 503 TPIAT recipients, 156 (31%) achieved insulin independence; of these, 45 (28.8%) experienced hypoglycemia, including 32 (20.5%) with level 2 hypoglycemia (< 54 mg/dL). Severe hypoglycemia events requiring external assistance occurred in 25% of affected individuals. Hypoglycemia developed a mean of 2.4 ± 2.2 years posttransplant, most commonly postprandial or exercise-related. Patients who developed hypoglycemia were older at the time of TPIAT (p = 0.036) and had higher preoperative BMI (p = 0.016) and a greater prevalence of malabsorptive disorders (p < 0.001), whereas islet yield and metabolic testing results were similar between patients with and without hypoglycemia. Most patients with hypoglycemia (78%) were managed with non-pharmacological interventions (dietary, continuous glucose monitoring); pharmacologic therapies included acarbose (22%), diazoxide (13%), and minidose glucagon (7%). Conclusions: Spontaneous hypoglycemia is a frequent, clinically relevant complication among insulin-independent TPIAT recipients. Older age, higher BMI, and malabsorptive disorders were associated with increased susceptibility. Routine surveillance, dietary counseling, and continuous glucose monitoring (CGM) are common components of management.