Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes

Not Applicable

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Healthy Subjects	ascorbic acid (Vitamin C)	Subjects received ascorbic acid (Vitamin C) infusion 1 g/kg (maximum 100gm
Diabetic Type II Subjects	ascorbic acid (Vitamin C)	Subjects received ascorbic acid (Vitamin C) infusion 1 g/kg (maximum 100gm

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures