Development of minimally invasive C-glucose breath test to examine different exogenous carbohydrate sources in patients with glycogen storage disease type Ia.

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 () is available to treat hypoglycemia, yet choice of carbohydrate to achieve a desirable glycemic control is debated.C-glucose breath test (C-GBT) can be used to examine glucose metabolism from different carbohydrate sources via CO in breath.

OBJECTIVES

Our objectives were: 1) establishing the use of a minimally invasive C-GBT to examine in vivo glucose metabolism in healthy adults, and 2) using C-GBT to measure utilization of the standard UCCS vs. in GSD Ia and healthy controls.

DESIGN

Ten healthy adults (6F: 4 M, 22-33y) underwent C-GBT protocol twice as a proof-of-principle, once with oral isotope dose (glucose 75 g + [U-C] d-glucose 75 mg) and once without isotope (only glucose 75 g) to test sensitivity of natural C-enrichment. Breath samples were collected at baseline and every 20 min for 240 min. Rate of CO 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). Three GSD Ia (12y, 13y, and 28y) and six healthy controls (2F: 4 M, 10-32y) underwent C-GBT protocol twice: with UCCS or (based on their current prescribed dose 42-100 g) after ~4 h fast based on our GSD Ia patients with fasting tolerance.

RESULTS

Maximum C-enrichments occurred at 200 min without and with [U-C] d-glucose in all healthy adults, suggesting natural enrichment is sensitive for the C-GBT. utilization was lower than UCCS utilization in 12y and 13y GSD Ia, but was similar in the 28y GSD Ia.

CONCLUSIONS

C-GBT is a novel minimally invasive functional test to examine glucose metabolism in GSD Ia, and test new products like , which has the potential to improve nutritional management and individualized carbohydrate supply in GSD.