Oxidative Stress, Type 2 Diabetes
Conditions
Keywords
Diabetes, MR imaging, Vitamin C
Brief summary
Oxidative stress has been implicated in the development and complications of diabetes. Hyperglycemia and insulin resistance or insufficiency in diabetes can cause oxidative stress by excessive reactive oxygen species and can increase damage and alter antioxidant status in nerve cells. Antioxidant defense mechanisms protect against damage or restore oxidative damage. Glutathione, a powerful antioxidant plays a key role in the first line of antioxidant defense and seems to be a sensitive indicator of oxidative stress in various diseases such as diabetes. Glutathione functions in the regeneration of vitamin C which is another crucial antioxidant. Both hyperglycemia and insulin insufficiency inhibit uptake of vitamin C. The brain contains measurable amounts of glutathione that contribute to the antioxidant pool in the brain and guards against disease processes that are caused by oxidative stress. Since the brain is the most highly oxidative organ in the body and highly susceptible to oxidative stress, with increasing impact on diabetes, biomarkers of oxidative stress in the brain through the use of novel magnetic resonance imaging techniques for glutathione and vitamin C will be studied.
Detailed description
The brain contains measurable amounts of glutathione that contribute to the antioxidant pool in the brain and guards against disease processes that are caused by oxidative stress. Since the brain is the most highly oxidative organ in the body and highly susceptible to oxidative stress, with increasing impact on diabetes, biomarkers of oxidative stress in the brain through the use of novel magnetic resonance imaging techniques for glutathione and vitamin C will be studied.
Interventions
BIOLOGICALascorbic acid (Vitamin C)
ascorbic acid IV 1 g/kg
Sponsors
In-Young Choi, Ph.D.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 30-55 years of age * Diabetic being treated with diet and any of the following: insulin, or other diabetic specific drug such as metformin, sulfonylurea or sitagliptin. * Healthy subjects age and gender matched to diabetes patient
Exclusion criteria
* Use of any anti-inflammatory or antioxidant medications other than small daily doses of Aspirin (ASA:325 mg) and a daily multivitamin * Co-existing chronic inflammatory conditions such as Crohn's disease, rheumatoid arthritis, chronic or acute infections * Any concurrent neurological disease except for mild diabetic autonomic or peripheral neuropathy * Postmeal C peptide \> 0.3 mg/dl * Normal healthy subjects who have any abnormal inflammatory marker, hyperlipidemia, or concurrent disease * Diseases associated with abnormal glutathione metabolism * Elevated serum creatinine levels, abnormal complete blood count (CBC), abnormal liver function tests or elevated serum homocysteine * Morbid obesity * History of hypoglycemic unawareness * Pregnant women and women who are breastfeeding * Patients with poor venous access * Smokers * Subject who consumes an excess of alcohol or abuses drugs * History or or presence of bleeding disorder or use of anticoagulant drug * History of oxalate renal calculi
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Vitamin C in Type 2 Diabetic Patients. | Pre-Vitamin C infusion | Concentrations of vitamin C were measured in the brains of type 2 Diabetic patients and healthy controls. |
| Quantify the Effect of Chronic Hyperglycemia on Cellular Uptake of Vitamin C Across the Blood-brain Barrier | 2 hour post infusion | Concentrations of vitamin C after IV infusion of Vitamin C were measured in the brains of patients with type 2 diabetes and healthy controls to examine whether the concentrations are different between two groups. |
Countries
United States
Participant flow
Pre-assignment details
All subjects were consented to participate in the study. After baseline information was gathered from labs, it was determined that seven subjects did not meet the inclusion criteria. They were excluded from completing the study.
Participants by arm
| Arm | Count |
|---|---|
| Diabetic Type II Subjects Subjects received ascorbic acid (Vitamin C) infusion 1 g/kg (maximum 100gm). | 16 |
| Health Subjects Subjects received ascorbic acid (Vitamin C) infusion 1 g/kg (maximum 100gm). | 19 |
| Total | 35 |
Baseline characteristics
| Characteristic | Health Subjects | Diabetic Type II Subjects | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 16 Participants | 35 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 7 | 48 years STANDARD_DEVIATION 5 | 47 years STANDARD_DEVIATION 6 |
| Region of Enrollment United States | 19 participants | 16 participants | 35 participants |
| Sex: Female, Male Female | 12 Participants | 7 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 19 |
| serious Total, serious adverse events | 0 / 16 | 0 / 19 |
Outcome results
Primary
Concentration of Vitamin C in Type 2 Diabetic Patients.
Concentrations of vitamin C were measured in the brains of type 2 Diabetic patients and healthy controls.
Time frame: Pre-Vitamin C infusion
Population: Determine cerebral concentrations of vitamin C. Data from one healthy subject were not usable due to subject's movement during MRI scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diabetic Type II Subjects | Concentration of Vitamin C in Type 2 Diabetic Patients. | 1.1 umol/g tissue | Standard Deviation 0.2 |
| Healthy Subjects | Concentration of Vitamin C in Type 2 Diabetic Patients. | 1.2 umol/g tissue | Standard Deviation 0.1 |
Primary
Quantify the Effect of Chronic Hyperglycemia on Cellular Uptake of Vitamin C Across the Blood-brain Barrier
Concentrations of vitamin C after IV infusion of Vitamin C were measured in the brains of patients with type 2 diabetes and healthy controls to examine whether the concentrations are different between two groups.
Time frame: 2 hour post infusion
Population: Data from one healthy subject were not usable due to subject's movement during MRI scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diabetic Type II Subjects | Quantify the Effect of Chronic Hyperglycemia on Cellular Uptake of Vitamin C Across the Blood-brain Barrier | 1.1 µmol/g tissue | Standard Deviation 0.2 |
| Healthy Subjects | Quantify the Effect of Chronic Hyperglycemia on Cellular Uptake of Vitamin C Across the Blood-brain Barrier | 1.4 µmol/g tissue | Standard Deviation 0.2 |