Urinary Vitamin C Loss in Diabetic Subjects

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00071526
First received: October 27, 2003
Last updated: May 9, 2014
Last verified: April 2014
  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

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

Estimated Enrollment: 99999999
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. Subjects with ischemic heart disease and/or peripheral artery disease are eligible for arm 1 of the protocol.
  • have serum creatinine < 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 insulin, 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 (for arm 1):

-Exclusion criteria will include the following:

  • significant organ malfunction including liver disease, pulmonary disease, stroke and anemia
  • serious or chronic illness or history of serious or chronic illness other than complications of diabetes
  • 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

EXCLUSION CRITERIA (for arms 2 and 3):

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071526

Contacts
Contact: Sebastian J Padayatty, M.D. (301) 496-1069 sebastianp@intra.niddk.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Sebastian J Padayatty, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00071526     History of Changes
Other Study ID Numbers: 040021, 04-DK-0021
Study First Received: October 27, 2003
Last Updated: May 9, 2014
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

Additional relevant MeSH terms:
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vitamins
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014