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 GSDIa patients is prioritized, because of ongoing treatment developments. Stable isotope tracers may enable reliable EGP monitoring.

OBJECTIVE: The aim of this study was to prospectively assessthe rate of appearance of endogenous glucose into the bloodstream (Ra) in GSDIa patients after a single oral d-[6,6-2H2]-glucose dose.

DESIGN: Ten adult GSDIa patients and ten age-, sex-, BMI-matched healthy volunteers (HV) were enrolled. For each participant, three oral glucose tracer tests were performed: 1) preprandial/fasted, 2) postprandial, and 3) randomly fed states. Dried blood spots were collected before d-[6,6-2H2]-glucose administration and 10, 20, 30, 40, 50, 60, 75, 90, 120 minutes thereafter.

RESULTS: Glucose Ra in fasted HV was consistent with previously reported data. The time-averaged glucose Ra was significantly higher in i) preprandial/fasted GSDIa patients than HV and ii) postprandial HV compared to fasted HV(p<0.05). A progressive decrease in glucose Ra was observed in preprandial/fasted GSDIa patients; the change in glucose Ra time-course was directly correlated with the change in capillary glucose (p<0.05).

CONCLUSIONS: This is the first study to quantify glucose Ra in GSDIa patients using oral d-[6,6-2H2] glucose. The test can reliably estimate EGP under conditions in which fasting tolerance is unaffected but does not discriminate between relative contributions of EGP (e.g., liver, kidney) and exogenous sources (e.g., dietary cornstarch). Future application is warranted for longitudinal monitoring after novel genome-based treatments in GSDIa patients in whom nocturnal dietary management can be discontinued.