Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia Estimated by Oral d-[6,6-²H₂]-glucose

Context: Glycogen storage disease type Ia (GSDIa) is an inborn metabolic disorder characterized by impaired endogenous glucose production (EGP). Monitoring of patients with GSDIa is prioritized because of ongoing treatment developments. Stable isotope tracers may enable reliable EGP monitoring.Objective: The aim of this study was to prospectively assess the rate of appearance of endogenous glucose into the bloodstream (R-a) in patients with GSDIa after a single oral d-[6,6-H-2(2)]-glucose dose.Methods: Ten adult patients with GSDIa and 10 age-, sex-, and body mass index-matched healthy volunteers (HVs) were enrolled. For each participant, 3 oral glucose tracer tests were performed: (1) preprandial/fasted, (2) postprandial, and (3) randomly fed states. Dried blood spots were collected before d-[6,6-H-2(2)]-glucose administration and 10, 20, 30, 40, 50, 60, 75, 90, and 120 minutes thereafter.Results Glucose R-a in fasted HVs was consistent with previously reported data. The time-averaged glucose R-a was significantly higher in (1) preprandial/fasted patients with GSDIa than HV and (2) postprandial HV compared with fasted HV(P < .05). A progressive decrease in glucose R-a was observed in preprandial/fasted patients with GSDIa; the change in glucose R-a time-course was directly correlated with the change in capillary glucose (P < .05).Conclusion This is the first study to quantify glucose R-a in patients with GSDIa using oral d-[6,6-H-2(2)] glucose. The test can reliably estimate EGP under conditions in which fasting tolerance is unaffected but does not discriminate between relative contributions of EGP (eg, liver, kidney) and exogenous sources (eg, dietary cornstarch). Future application is warranted for longitudinal monitoring after novel genome based treatments in patients with GSDIa in whom nocturnal dietary management can be discontinued.