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Urinary Vitamin C Loss in Diabetic Subjects
This study is currently recruiting participants.
Verified by National Institutes of Health Clinical Center (CC), March 2009
First Received: October 27, 2003   Last Updated: April 24, 2009   History of Changes
Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00071526
  Purpose

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
Diabetes Mellitus

Study Type: Observational
Official Title: Urinary Vitamin C Loss in Subjects With and Without Diabetes

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 150
Study Start Date: October 2003
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

We propose to study 150 male and female subjects between the ages of 18 and 65. This will include 50 healthy subjects and 100 subjects with type 1 or type 2 diabetes. To be included in the study, study subjects should:

  • Be non smokers and be in good general health.
  • Have no significant illnesses other than the complications of diabetes mellitus but should not have neuropathy affecting the functioning of internal organs such as the stomach and urinary bladder.
  • Have serum creatinine less than 2.
  • Be normotensive at the time of the study, with a blood pressure less than or equal to 140/90.

Acceptable medications include insulin and ACE inhibitors or ARBs for type 1 diabetes and oral hypoglycemic agents and ACE inhibitors or ARBs in the case of type 2 diabetes. Type 1 and type 2 diabetic subjects on aspirin are also eligible provided they are not taking it for known ischemic heart disease or cerebrovascular disease. 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:

Exclusion criteria will include the following:

  • Significant organ malfunction including liver disease, pulmonary disease, ischemic heart disease, heart failure, stroke, peripheral vascular disease, and anemia.
  • Other serious or chronic illness; history of serious or chronic illness; coronary artery disease, or peripheral vascular disease.
  • Pregnancy or acromegaly.
  • Alcohol abuse, drug addiction or the use of illegal drugs.
  • Use of vitamin supplements within 2 weeks prior to sample procurement.
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00071526

Contacts
Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov
Contact: TTY 1-866-411-1010

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Additional Information:
Publications:
Study ID Numbers: 040021, 04-DK-0021
Study First Received: October 27, 2003
Last Updated: April 24, 2009
ClinicalTrials.gov Identifier: NCT00071526     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Vitamin C
Diabetes Mellitus
Proteinuria
Plasma Concentrations
Renal Threshold
Diabetes Type II
Diabetes Type I
Healthy Volunteer
HV

Study placed in the following topic categories:
Metabolic Diseases
Antioxidants
Diabetes Mellitus
Endocrine System Diseases
Trace Elements
Healthy
Vitamin C
Proteinuria
Vitamins
Diabetes Mellitus, Type 2
Micronutrients
Endocrinopathy
Glucose Metabolism Disorders
Metabolic Disorder
Ascorbic Acid

Additional relevant MeSH terms:
Metabolic Diseases
Antioxidants
Molecular Mechanisms of Pharmacological Action
Growth Substances
Physiological Effects of Drugs
Diabetes Mellitus
Endocrine System Diseases
Protective Agents
Pharmacologic Actions
Vitamins
Micronutrients
Glucose Metabolism Disorders
Ascorbic Acid

ClinicalTrials.gov processed this record on September 03, 2009