Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes

Conditions
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Type 2 Diabetes, Oxidative Stress

Intervention / Treatment
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* Biological: ascorbic acid (Vitamin C)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diabetic Type II Subjects<br>Subjects received ascorbic acid (Vitamin C) infusion 1 g/kg (maximum 100gm | Biological: ascorbic acid (Vitamin C)<br>* ascorbic acid IV 1 g/kg<br>* Other names: Vitamin C;|
| Experimental: Healthy Subjects<br>Subjects received ascorbic acid (Vitamin C) infusion 1 g/kg (maximum 100gm | Biological: ascorbic acid (Vitamin C)<br>* ascorbic acid IV 1 g/kg<br>* Other names: Vitamin C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Pre-Vitamin C infusion | 
| 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. | 2 hour post infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MR imaging, Diabetes, Vitamin C