Abstract
Objectives
The objectives of the current study were: 1) to establish the use of ,13C-Glucose Breath Test (,13C-GBT) and its oxidation to ,13CO2 as a minimally invasive technique to examine in vivo glucose oxidation in healthy adults, and 2) to measure the utilization of uncooked cornstarch (UCCS) and Glycosade® in patients with glycogen storage disease type Ia (GSD-Ia) and healthy controls using ,13C-GBT, based on the natural enrichment of ,13C in UCCS and Glycosade®.
Methods
Experiment 1- Ten healthy adults (22 – 33y) underwent ,13C-GBT protocols twice as a proof-of-principle, once without oral isotope dose (only D-glucose 75 g/d) and once with isotope (D-glucose 75 g/d + U-,13C-glucose 75 mg/d). Breath samples were collected at baseline and every 20 min for 240 min to measure ,13CO2. Experiment 2- Two patients (12 and 28y) with GSD-Ia and five healthy controls (10 – 32y) underwent ,13C-GBT protocols twice. Subjects received UCCS or Glycosade® orally (based on their current prescribed dose 42 – 100 g) after a 4 hour fast according to GSD-Ia fasting tolerance. Breath samples were collected at baseline and every 30 min for 240 min. ,13CO2 oxidation of glucose from UCCS and Glycosade® were measured using an isotope ratio mass spectrometer and compared using a paired t-test. Blood glucose was measured using a glucometer hourly to test hypoglycemia (≤3.4 mmol/L).
Results
Results 1- The mean rate of ,13CO2 in all healthy adults from D-glucose without U-,13C-glucose 0.435 ± 0.162 was significantly lower than the mean rate of ,13CO2 in the same group with U-,13C-glucose 3.518 ± 0.988. The peak occurred at 200 minutes in all healthy adults without and with U-,13C-glucose. Results 2- Glucose oxidation from Glycosade® was lower than glucose oxidation from UCCS in the 12y GSD-Ia. Glucose oxidation from UCCS and Glycosade® remained the same in the 28y GSD-Ia. However, oxidation of glucose by the 28y GSD-Ia for both starches displayed a higher rate, compared to age matched controls.
Conclusions
Our results show that the minimally invasive,13C-GBT test over 4 hours can be useful to examine glucose metabolism from various exogenous carbohydrate sources in GSD. Future studies are needed to use ,13C-GBT in response to different doses to determine optimal glucose management in GSD patients.
Funding Sources
Saudi Arabian Cultural Bureau, Ottawa and BC Children's Hospital Research Institute.
Development of Minimally Invasive 13C-Glucose Breath Test to Examine Different Dietary Therapies in Patients with Glycogen Storage Disorders
