Urinary Vitamin C Loss in Diabetic Subjects

Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
Overall Status
Recruiting
CT.gov ID
NCT00071526
Collaborator
(none)
5,000
Enrollment
1
Location

Study Details

Study Description

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 vitamin C concentrations in patients with type 1 and type 2 diabetes and in matched healthy research subjects. Vitamin C concentrations in plasma, neutrophils (as a proxy for tissue concentrations) and in urine will be measured in outpatients. In those willing to be admitted to the Clinical Center, we will measure 24-hour urinary excretion of vitamin C while on a vitamin C free diet, and creatinine clearance, a measure of glomerular filtration rate. On day 2 of the inpatient study, subjects will receive a single 200mg dose of oral vitamin C and we will measure vitamin C concentrations in frequent blood and urine samples to determine the renal threshold and relative bioavailability for vitamin C. Single nucleotide polymorphisms (SNPs) will be determined in genomic DNA responsible for the two proteins mediating sodium-dependent vitamin C transport, SVCT1 and SVCT2. If low plasma and high urine vitamin C concentrations are found in diabetic subjects, further studies will be needed to explore mechanisms and to determine recommended dietary allowances for this patient population.

Condition or DiseaseIntervention/TreatmentPhase

    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 vitamin C concentrations in patients with type 1 and type 2 diabetes and in matched healthy research subjects. Vitamin C concentrations in plasma, neutrophils (as a proxy for tissue concentrations) and in urine will be measured in outpatients. In those willing to be admitted to the Clinical Center, we will measure 24-hour urinary excretion of vitamin C while on a vitamin C free diet, and creatinine clearance, a measure of glomerular filtration rate. On day 2 of the inpatient study, subjects will receive a single 200mg dose of oral vitamin C and we will measure vitamin C concentrations in frequent blood and urine samples to determine the renal threshold and relative bioavailability for vitamin C. Single nucleotide polymorphisms (SNPs) will be determined in genomic DNA responsible for the two proteins mediating sodium-dependent vitamin C transport, SVCT1 and SVCT2. If low plasma and high urine vitamin C concentrations are found in diabetic subjects, further studies will be needed to explore mechanisms and to determine recommended dietary allowances for this patient population.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    5000 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Urinary Vitamin C Loss in Subjects With and Without Diabetes
    Actual Study Start Date :
    Apr 11, 2006

    Arms and Interventions

    ArmIntervention/Treatment
    Diabetes Type I

    Subjects with Type I diabetes mellitus

    Diabetes Type II

    Subjects with Type II diabetes mellitus

    Healthy Volunteers

    Healthy Volunteers

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. Urinary vitamin C concentration [end of study]

      Measurements of urinary vitamin c concentrations in diabetic subjects as compared to healthy controls.

    2. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    • INCLUSION CRITERIA:

    We propose to study of five thousand male and female subjects between the ages of 18 and 65. This will include healthy subjects and subjects with type 1 or type 2 diabetes. To be included in the study, study subjects should

    • be in good general health

    • have no significant illnesses that compromise clinical stability other than the complications of diabetes mellitus alone or in the context of metabolic syndrome. Subjects with ischemic heart disease and/or peripheral artery disease are eligible for arm 1 of the protocol.

    • have serum creatinine < 2.5

    • for healthy volunteers, be normotensive at the time of the study, with a blood pressure less than or equal to 140/90

    • for diabetic subjects, blood pressure less than or equal to 170/95 as long as clinically stable and in usual state of health, for example, no chest pain, shortness of breath, headache, syncope or fatigue

    The aim of this study is to determine whether diabetic subjects lose vitamin C in the urine in their normal clinical condition (i.e. while on treatment) and not in the native untreated state of uncontrolled hyperglycemia. Therefore the patients will not discontinue medication.

    EXCLUSION CRITERIA (for arm 1):
    Exclusion criteria will include the following:
    • significant organ malfunction leading to clinical instability including liver disease, pulmonary disease, stroke and anemia at investigator discretion

    • serious or chronic illness or history of serious or chronic illness resulting in clinical instability other than complications of diabetes

    • pregnancy

    • alcohol abuse, drug addiction or the use of illegal drugs

    • positive HIV or hepatitis (B or C) screening tests (subjects will be notified of these test results).

    • presence of other concomitant conditions which in the judgment of the investigators can influence vitamin C metabolism or vitamin C renal handling

    EXCLUSION CRITERIA (for arms 2 and 3):
    Exclusion criteria will include 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

    • alcohol abuse, drug addiction or the use of illegal drugs

    • positive HIV or hepatitis (B or C) screening tests (subjects will be notified of these test results).

    • presence of other concomitant conditions which in the judgment of the investigators can influence vitamin C metabolism or vitamin C renal handling

    For inpatient subjects, an additional exclusion criterion is consumption during the hospitalization of any foods or beverages other than those in the vitamin C free diet.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1National Institutes of Health Clinical Center, 9000 Rockville PikeBethesdaMarylandUnited States20892

    Sponsors and Collaborators

    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Investigators

    • Principal Investigator: Ifechukwude C Ebenuwa, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    ClinicalTrials.gov Identifier:
    NCT00071526
    Other Study ID Numbers:
    • 040021
    • 04-DK-0021
    First Posted:
    Oct 28, 2003
    Last Update Posted:
    Oct 29, 2021
    Last Verified:
    Jun 30, 2021
    Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 29, 2021