RESUMO
Background: Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive disorder caused by deficiency of glucose-6-phosphatase (G6Pase), resulting in fasting hypoglycemia. Dietary treatment with provision of uncooked cornstarch (UCCS) or a novel modified cornstarch (Glycosade®) is available to treat hypoglycemia, yet choice of carbohydrate to achieve a desirable glycemic control is debated.13C-glucose breath test (13C-GBT) can be used to examine glucose metabolism from different carbohydrate sources via 13CO2 in breath. Objectives: Our objectives were: 1) establishing the use of a minimally invasive 13C-GBT to examine in vivo glucose metabolism in healthy adults, and 2) using 13C-GBT to measure utilization of the standard UCCS vs. Glycosade® in GSD Ia and healthy controls. Design: Experiment 1- Ten healthy adults (6F: 4 M, 22-33y) underwent 13C-GBT protocol twice as a proof-of-principle, once with oral isotope dose (glucose 75 g + [U-13C6] d-glucose 75 mg) and once without isotope (only glucose 75 g) to test sensitivity of natural 13C-enrichment. Breath samples were collected at baseline and every 20 min for 240 min. Rate of CO2 production was measured at 120 min using indirect calorimetry. Finger-prick blood glucose was measured using a glucometer hourly to test hypoglycemia (glucose <4 mmol/L). Experiment 2- Three GSD Ia (12y, 13y, and 28y) and six healthy controls (2F: 4 M, 10-32y) underwent 13C-GBT protocol twice: with UCCS or Glycosade® (based on their current prescribed dose 42-100 g) after ~4 h fast based on our GSD Ia patients with fasting tolerance. Results: Findings 1- Maximum 13C-enrichments occurred at 200 min without and with [U-13C6] d-glucose in all healthy adults, suggesting natural enrichment is sensitive for the 13C-GBT. Findings 2- Glycosade® utilization was lower than UCCS utilization in 12y and 13y GSD Ia, but was similar in the 28y GSD Ia. Conclusions: 13C-GBT is a novel minimally invasive functional test to examine glucose metabolism in GSD Ia, and test new products like Glycosade®, which has the potential to improve nutritional management and individualized carbohydrate supply in GSD.