Development of Minimally Invasive 13C-Glucose Breath Test to Examine Different Dietary Therapies in Patients with Glycogen Storage Disorders

Abstract

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.