Clinical trial NCT00071526: Urinary Vitamin C Loss in Diabetic Subjects
Official title: Urinary Vitamin C Loss in Subjects With and Without Diabetes
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diabetes
Keywords: Renal Threshold
Diabetes Mellitus
Proteinuria
Plasma Concentrations
Healthy Volunteer
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2003-10-28
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Community sample.

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.

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

Primary outcomes:
measure: Plasma, neutrophil and RBC Vitamin C concentrates
timeFrame: end of study
Secondary outcomes:
measure: Urinary vitamin C concentration
timeFrame: end of study
measure: Determine the renal threshold and relative bioavailability for vitamin C
timeFrame: end of study
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Ifechukwude C Ebenuwa, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.