Deficient endogenous glucose production during exercise after total pancreatectomy/islet autotransplantation

Context: Total pancreatectomy followed by intrahepatic islet autotransplantation (TP/IAT) is performed to alleviate severe, unrelenting abdominal pain caused by chronic pancreatitis, to improve quality of life, and to prevent diabetes. Objective: To determine the cause of exercise-induced hypoglycemia that is a common complaint in TP/IAT recipients. Design: Participants completed 1 hour of steady-state exercise. Setting: Hospital research unit. Patients and Other Participants: We studied 14 TP/IAT recipients and 10 age- and body mass index-matched control subjects. Interventions: Peak oxygen uptake (VO2) was determined via a symptom-limited maximal cycle ergometer test. Fasted subjects then returned for a primed [6,6-2H2]-glucose infusion to measure endogenous glucose production while completing 1 hour of bicycle exercise at either 40% or 70% peak VO2. Main Outcome Measures: Blood samples were obtained to measure glucose metabolism and counterregulatory hormones before, during, and after exercise. Results: Although the Borg Rating of Perceived Exertion did not differ between recipients and control subjects, aerobic capacity was significantly higher in controls than in recipients (40.462.0 vs 27.2 6 1.4 mL/kg per minute; P , 0.001). This difference resulted in workload differences between control subjects and recipients to reach steady-state exercise at 40% peak VO2 (P = 0.003). Control subjects significantly increased their endogenous glucose production from 12.0 6 1.0 to 15.2 6 1.0 mmol/kg per minute during moderate exercise (P = 0.01). Recipients did not increase endogenous glucose production during moderate exercise (40% peak VO2) but succeeded during heavy exercise, from 10.1 6 0.4 to 14.8 6 2.0 mmol/kg per minute (70% peak VO2; P = 0.001). Conclusions: Failure to increase endogenous glucose production during moderate exercise may be a key contributor to the hypoglycemia TP/IAT recipients experience.