Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes

Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes

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.

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.

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