Vitamins C and Vitamin E and Cardiovascular Risk
Vitamins C and Vitamin E and Cardiovascular Risk
The proposed study will examine the hypothesis that vitamin C and vitamin E given to type 2
 diabetic individuals will provide effective anti-inflammatory, anti-thrombotic, and
 anti-oxidative atherosclerotic protection when administered at the optimal dose as determined
 by surrogate markers of inflammation, hypercoagulability, and oxidation.
This American Diabetes Association research project is to determine why there are discrepant
 results between individual studies of Vitamin E and C in both animals and humans compared
 with the results obtained in large randomized human trials using Vitamin E.

 Subjects: The study will enroll subjects (both men and women) with type 2 diabetes of at
 least six months duration. An outpatient screening test will utilize the following: a
 complete history and physical examination, an EKG, a urine hcG (only for women of
 childbearing age), and the following blood tests: CBC, Chem-20, lipid profile, hemoglobin
 A1C, and C-peptide stimulation test. Subjects will be excluded if they have known vascular
 disease, uncontrolled hypertension (>140/90 mmHg) or marked hyperlipidemia (serum low density
 lipoprotein > 4.1 mmol/L or serum triglycerides > 7.8 mmol/L). Eligible patients must have
 normal electrocardiogram tracings and normal screening test results (described above). Other
 important exclusion criteria are cigarette smoking, volunteers taking Coumadin, and recent
 use of antioxidant supplements or aspirin. All patients will provide written informed consent
 before enrollment as approved by the University of New Mexico Human Research Review
 Committee.

 Surrogate Markers: Based on our preliminary data and the published medical literature, it is
 extremely likely that vitamins C and E will modify all three contributors to atherosclerosis:
 Oxidative stress, Hypercoagulability, and Inflammation. Therefore, as shown in the table
 above, we have included standard surrogate markers for all three of these contributors.

 Specific Aim: Determine the optimal oral dose of vitamin C and vitamin E relative to the
 consumption of an atherogenic high fat supper in type 2 diabetic individuals. These data are
 necessary in order to design prospective clinical trials in which vitamins are given to
 prevent or delay atherosclerotic events. One reason that published clinical trials
 demonstrate conflicting results may be the different dosages of vitamins that have been
 utilized. In the following study, we will utilize our high fat (simulated Big Mac) meal to
 assess the beneficial effects of these vitamins on surrogate markers of atherosclerosis.
 Three dosages of vitamins will be utilized in order to determine the optimal dosage.

 The three dosages to be tested are 1) low dose - vitamin C 250mg, vitamin E 200 IU 2) medium
 dose - vitamin C 500 mg, vitamin E 400 IU and 3) high dose - vitamin C 1000mg, vitamin E 800
 IU. The results will be compared to a control meal study in which only placebo (hence, no
 vitamins) is administered. The vitamins will be administered before breakfast on each study
 day.
Inclusion Criteria:

 -  The study will enroll subjects, both men and women with type 2 diabetes of at least
 six months duration. The age of enrolled subjects will range from 21-60 years old. An
 HbA1c blood test must show that the person's diabetes is under control. Eligible
 subjects must have normal electrocardiogram tracings and normal hematological,
 electrolyte and liver laboratory results at screening. Females of childbearing age
 must agree to use an effective form of birth control throughout the study period.

 Exclusion Criteria:

 -  Subjects will be excluded if they have known vascular disease, uncontrolled
 hypertension (>140/90 mmHg), marked hyperlipidemia (serum low density lipoprotein >
 4.1 mmol/L or serum triglycerides > 7.8 mmol/L), and a body mass index greater than 40
 kg/m2 (range 27-40). Other important exclusion criteria are cigarette smoking,
 volunteers taking Coumadin, and recent use of antioxidant supplements or aspirin.
 Females who are pregnant or breastfeeding will be excluded. People cannot participate
 in this study if they are taking medications (other than antidiabetic medications)
 which may affect blood sugar.