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

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 Disease	Intervention/Treatment	Phase
Diabetes

Detailed Description

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

Arm	Intervention/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

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

Urinary vitamin C concentration [end of study]
Measurements of urinary vitamin c concentrations in diabetic subjects as compared to healthy controls.
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.