Official Title
Urinary Vitamin C Loss in Subjects With and Without Diabetes
Brief Title
Urinary Vitamin C Loss in Diabetic Subjects
Protocol ID
NCT00071526
Lead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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.
Study Period
Enrollment Count
5,000 participants
Eligibility 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)
Exclusion criteria will include the following:
- Unable or unwilling to provide a signed and dated informed consent form
- Unable or unwilling to comply with study procedures and lifestyle considerations
EXCLUSION CRITERIA (for inpatient studies, arms 2 and 3)
Study participants interested in participating in Arms 2 and/or 3 will be excluded from
this further participation if they meet any of the following:
- significant organ malfunction leading to clinical instability including liver
disease, pulmonary disease, ischemic heart disease, heart failure, stroke,
peripheral vascular disease, and anemia at investigator discretion
- other serious or chronic illness; history of serious or chronic illness; coronary
artery disease, or peripheral vascular disease resulting in clinical instability
- pregnancy or lactation
- presence of other conditions which, in the judgment of the investigators, can
influence vitamin C metabolism or vitamin C renal handling
Filters
Diabetes
RECRUITING
ADULT
OLDER_ADULT