Urinary Vitamin C Loss in Diabetic Subjects

Diabetes Clinical Trial

Official title:

Urinary Vitamin C Loss in Subjects With and Without Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00071526
• Other study ID #: 040021
• Secondary ID: 04-DK-0021
• Status: Recruiting
• Start date: April 11, 2006

Study information

• Verified date: June 11, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Irene T Rozga, R.N.
• Phone: (301) 496-1069
• Email: irene.rozga[@]nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

• 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.

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma, neutrophil and RBC Vitamin C concentrates	Measurements of plasma, neutrophil and red blood cell vitamin c concentrations in diabetic subjects as compared to healthy controls.	end of study
Secondary	Urinary vitamin C concentration	Measurements of urinary vitamin c concentrations in diabetic subjects as compared to healthy controls.	end of study
Secondary	Determine the renal threshold and relative bioavailability for vitamin C	Calculate renal threshold of vitamin C in diabetic subjects as compared to healthy controls.	end of study

External Links

•   NIH Clinical Center Detailed Web Page