Continuous Glucose Monitoring-Driven Personalization of Cornstarch Therapy in Glycogen Storage Disease: A...

Hepatic glycogen storage diseases (GSD), including types Ia, Ib, and IXa, are rare inherited disorders characterized by impaired hepatic glucose homeostasis. In GSD Ia, deficiency of glucose-6-phosphatase results in recurrent hypoglycemia and metabolic disturbances. Uncooked cornstarch (UCCS) is the standard therapy due to its slow digestion and sustained glucose release; however, dosing requirements vary according to age, digestion rate, metabolic demand, and lifestyle. Despite the central role of UCCS in long-term management, real-world data describing extended continuous glucose monitoring (CGM) patterns in hepatic GSD are extremely limited, and objective evidence guiding individualized dose adjustment remains scarce. This study examined CGM profiles in patients with hepatic GSD receiving long-term UCCS therapy and assessed the clinical utility of CGM in guiding individualized dosing adjustments.

We performed a retrospective, multi-year analysis of CGM data from 32 patients with hepatic GSD treated with UCCS. CGM traces were processed using 15-minute resampling, constrained interpolation, and physiologic clipping (40-400 mg/dL). Data were segmented into non-overlapping, calendar-anchored 7- and 14-day windows (anchor at 00:00) and retained when coverage was ≥70%. Per window, we calculated time in range (TIR, 70-150 mg/dL), time below range (TBR, <70 mg/dL), time above range (≥150 mg/dL), coefficient of variation, nocturnal TBR (00:00-06:00), and hypoglycemia burden [area under the curve (AUC) <70 mg/dL].

During routine clinic follow-up, CGM-informed, patient-specific UCCS and dietary adjustments maintained high TIR and low glycemic variability. Growth parameters and liver enzyme levels remained within normal limits. Episodes of recurrent nocturnal hypoglycemia identified on CGM prompted targeted modifications of UCCS dosing.

A CGM-guided approach facilitates personalized UCCS management in hepatic GSD. Systematic review of TIR, nocturnal TBR, and AUC <70 mg/dL, alongside growth and liver assessments, provides a practical framework for optimizing long-term metabolic stability.