(P22-032-23) Study Protocol NCT02107976: Effects of Dynamic Hyperglycemia on Vitamin C Physiology in People With Diabetes

Objectives: Diabetic individuals have lower plasma and red blood cell (RBC) concentrations compared to people without diabetes. Recent data indicate that diabetic individuals have inappropriate loss of vitamin C via the urine, described as a renal leak (PMID: 35537862). Low vitamin C concentrations in RBC have also been linked to decreased RBC deformability/increased rigidity (PMID: 26870799). We hypothesized that hyperglycemia and renal leak contribute to the low plasma and RBC concentrations in diabetic individuals.

Methods: To test the hypothesis, we launched a clinical protocol (NCT02107976) in diabetic subjects to test whether real-time changes in glycemia (dynamic hyperglycemia) induce concurrent changes in plasma, RBC and urine vitamin C concentrations, and RBC deformability. Individuals with type 2 diabetes who have hemoglobin A1C values < 12 are selected to participate in two inpatient visits at the NIH Clinical Research Center, with at least 12 weeks in between visits.

Results: For each visit, subjects undergo 48 hours of serial sampling. The first 24-hour sampling period is with minimal hyperglycemia, using insulin or similar therapies to control blood glucose as tightly as feasible. The second 24-hour sampling period is with controlled hyperglycemia, with blood glucose values up to 400 mg/dL for a period of 9 hours. Hyperglycemia is induced by high carbohydrate ingestion and managed with insulin or other therapies as needed. On both sampling days we measure vitamin C concentrations in the plasma, RBC, and urine using high performance liquid chromatography. RBC deformability is measured using ektacytometry. Blood glucoses are measured using an implanted continuous glucose monitor, point of care glucose testing, and blood chemistry analyses. After their first inpatient visit, participants are supplemented with 500 mg vitamin C twice daily. After 12 weeks of supplementation, participants return for a second inpatient visit. To date, 3 subjects have completed this study, with a target of 12 subjects completing all study phases.

Conclusions: Findings will allow us to learn whether there are acute or chronic relationships between hyperglycemia, vitamin C concentrations, and RBC deformability. To our knowledge, this is the first study of controlled dynamic hyperglycemia induced by foods in humans with diabetes.

Funding Sources: NIDDK, NIH