Urinary Vitamin C Loss in Diabetic Subjects

Official title

Urinary Vitamin C Loss in Subjects With and Without Diabetes

Overview

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.

Primary outcome measures

• Plasma, neutrophil and RBC Vitamin C concentrates [Time frame: end of study]

Secondary outcome measures (2)

• Urinary vitamin C concentration [Time frame: end of study]
• Determine the renal threshold and relative bioavailability for vitamin C [Time frame: end of study]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

United States · 1 center

• National Institutes of Health Clinical Center — Bethesda

Publications

• Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med. 1986 Apr 3;314(14):892-902. doi: 10.1056/NEJM198604033141407. No abstract available. PMID 3513016
• Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA. 1983 Jun 3;249(21):2917-21. PMID 6842805
• Fata FT, Herzlich BC, Schiffman G, Ast AL. Impaired antibody responses to pneumococcal polysaccharide in elderly patients with low serum vitamin B12 levels. Ann Intern Med. 1996 Feb 1;124(3):299-304. doi: 10.7326/0003-4819-124-3-199602010-00003. PMID 8554224
• Ebenuwa I, Violet PC, Tu H, Lee C, Munyan N, Wang Y, Niyyati M, Patra K, Wilkins KJ, Parrow N, Levine M. Altered RBC deformability in diabetes: clinical characteristics and RBC pathophysiology. Cardiovasc Diabetol. 2024 Oct 18;23(1):370. doi: 10.1186/s12933-024-02453-2. PMID 39425096

Identifiers

NCT: NCT00071526 · 040021 · 04-DK-0021

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗