Diabetes
Conditions
Keywords
Renal Threshold, Diabetes Mellitus, Proteinuria, Plasma Concentrations, Healthy Volunteer
Brief summary
Several studies have reported that diabetic subjects have lower plasma vitamin C concentrations than non-diabetic subjects. Although urinary vitamin C loss in diabetic subjects was reported to be increased in two studies, these are difficult to interpret due to lack of controlled vitamin C intake, inadequate sampling, lack of control subjects, or methodology uncertainties in vitamin C assay and sample processing. Consequently, it is unclear whether diabetic subjects truly have both low plasma and high urine vitamin C concentrations. We propose that low plasma vitamin C concentrations in diabetic subjects are due in part to inappropriate renal loss of vitamin C in these subjects but not in healthy controls. We will study nondiabetic controls and cohorts with diabetes. Vitamin C concentrations in plasma, RBCs, and urine will be measured in outpatients. In those willing to be admitted to the Clinical Center, we will measure vitamin C pharmacokinetics to determine the relative bioavailability for vitamin C in individuals with and without abnormal urinary loss of vitamin C (or renal leak). Single nucleotide polymorphisms (SNPs) will be determined in genomic DNA responsible for the two proteins mediating sodium dependent vitamin C transport, SVCT1 and SVCT2. We will also explore mechanisms underlying abnormal urinary vitamin C loss.
Detailed description
Several studies have reported that diabetic subjects have lower plasma vitamin C concentrations than non-diabetic subjects. Although urinary vitamin C loss in diabetic subjects was reported to be increased in two studies, these are difficult to interpret due to lack of controlled vitamin C intake, inadequate sampling, lack of control subjects, or methodology uncertainties in vitamin C assay and sample processing. Consequently, it is unclear whether diabetic subjects truly have both low plasma and high urine vitamin C concentrations. We propose that low plasma vitamin C concentrations in diabetic subjects are due in part to inappropriate renal loss of vitamin C in these subjects but not in healthy controls. We will study nondiabetic controls and cohorts with diabetes. Vitamin C concentrations in plasma, RBCs, and urine will be measured in outpatients. In those willing to be admitted to the Clinical Center, we will measure vitamin C pharmacokinetics to determine the relative bioavailability for vitamin C in individuals with and without abnormal urinary loss of vitamin C (or renal leak). Single nucleotide polymorphisms (SNPs) will be determined in genomic DNA responsible for the two proteins mediating sodium dependent vitamin C transport, SVCT1 and SVCT2. We will also explore mechanisms underlying abnormal urinary vitamin C loss.
Interventions
None listed
Sponsors
Study design
Eligibility
Inclusion criteria
* INCLUSION CRITERIA: To be included in the study, study subjects should be: * Aged 18-65 years. * Either: * Have no diagnosis of diabetes: "nondiabetic controls", or * Have a diagnosis in their medical history of either Type 1 or Type 2 diabetes
Exclusion criteria
(for outpatient study, arm 1)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma, neutrophil and RBC Vitamin C concentrates | end of study | Measurements of plasma, neutrophil and red blood cell vitamin c concentrations in diabetic subjects as compared to healthy controls. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary vitamin C concentration | end of study | Measurements of urinary vitamin c concentrations in diabetic subjects as compared to healthy controls. |
| Determine the renal threshold and relative bioavailability for vitamin C | end of study | Calculate renal threshold of vitamin C in diabetic subjects as compared to healthy controls. |
Countries
United States
Contacts
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)