urinary vitamin c loss in diabetic subjects

Conditions: Diabetes

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.

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.

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

Keywords: renal threshold diabetes mellitus proteinuria plasma concentrations healthy volunteer