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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Oxidative Stress
• Intervention / Treatment: Biological: ascorbic acid (Vitamin C)

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diabetic Type II Subjects; Subjects received ascorbic acid (Vitamin C) infusion 1 g/kg (maximum 100gm	Biological: ascorbic acid (Vitamin C); ascorbic acid IV 1 g/kg; Other Names: Vitamin C
Experimental: Healthy Subjects; Subjects received ascorbic acid (Vitamin C) infusion 1 g/kg (maximum 100gm	Biological: ascorbic acid (Vitamin C); ascorbic acid IV 1 g/kg; Other Names: Vitamin C

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: In-Young Choi, Ph.D.
• Investigators: Principal Investigator: In-Young Choi, PhD, Un iversity of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: February 15, 2009
• First Submitted That Met QC Criteria: February 17, 2009
• First Posted (Estimate): February 18, 2009

Study Record Updates

• Last Update Posted (Actual): May 3, 2018
• Last Update Submitted That Met QC Criteria: April 2, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes; Vitamin C; MR imaging
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Antioxidants; Vitamins; Ascorbic Acid
• Other Study ID Numbers: 11119 (DAIDS ES Registry Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No, there is not a plan to share individual data.