Glutathione Metabolism in Adolescents With Type 1 Diabetes - Study B

Regulation of Glutathione Homeostasis in Adolescents With Type 1 Diabetes - Study B

Glutathione is normally present at high levels in the blood and plays an important role in the body's defense against oxidative stress, that is, against the damage caused to the body by several reactive oxygen species produced by the metabolism of most nutrients, including glucose. Glutathione is a small peptide made from 3 amino acids, glutamate, cysteine, and glycine.

This study is looking at how blood sugar levels may affect the way glutathione is made and used by the body. Since glutathione is continuously synthesized and broken down, the amount of glutathione present in the blood depends on the balance between its rate of synthesis and its rate of use.

In earlier studies, we found that in poorly controlled diabetic teenagers, glutathione was low, not because it was not produced fast enough, but because it was used at an excessive rate. In this study, we want to find out whether improving blood sugar control will increase glutathione levels, and, if so, how long this will take. We also hope to find out if oral supplementation with a mixture of several antioxidant vitamins and minerals will increase glutathione levels more than taking a placebo.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Dietary supplement: Antioxidant supplement; Other: Diabetes treatment; Drug: Regular Insulin

Detailed Description

Forty adolescents with T1D will undergo a measurement of blood glutathione concentration and markers of oxidative stress (plasma protein-bound 3-nitrotyrosine, and urinary 8OH-2-dG, and F2-isoprostane excretion, markers of oxidative damage to protein, DNA and lipids, respectively) while at near normoglycemia, on two separate occasions:

• first, when in poor glucose control (HbA1c>7.5%); and
• secondly, after 3 to 9 months months of improved blood glucose control, along with the administration of either a placebo, or a mixture of antioxidant minerals and vitamins based on a randomization scheme.

Between the two metabolic study days, patients will receive the same intensified diabetes regimen consisting of education and counseling, home blood glucose monitoring, multiple daily insulin injections (MDI), diet plan, and frequent phone contact with a certified diabetes educator.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Type 1 diabetes, using usual criteria such as: glycosuria, hyperglycemia prior to treatment
• BMI <25 kg/m2
• Age 12-21
• HbA1c>7.5%
• No evidence of diabetic complications
• Written informed consent from parents or legal guardian, and assent from patient

Exclusion Criteria:

• Presence of significant anemia (hemoglobin <11g/dL)
• Presence of intercurrent illness such as infection
• Presence of chronic disease such as other endocrine deficiency, chronic respiratory or cardiac disease
• Chronic use of medication other than insulin
• Use of vitamin or mineral supplements within 2 weeks of study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Antioxidant supplement; 1 capsule daily with dinner; Other: Diabetes treatment; Intensification of diabetes treatment regimen, including education and counseling, home blood glucose monitoring, multiple daily insulin injections (MDI), diet plan, and frequent phone contact with a certified diabetes educator; Drug: Regular Insulin; Regular Insulin, IV, to maintain blood glucose in normoglycemic range (70-140) during metabolic study
Active Comparator: Antioxidant Supplement; Vitamin C 250 mg; beta-carotene 6 mg; vitamin E 30 mg; selenium 100 mcg; zinc 20 mg	Dietary supplement: Antioxidant supplement; 1 capsule daily with dinner; Other: Diabetes treatment; Intensification of diabetes treatment regimen, including education and counseling, home blood glucose monitoring, multiple daily insulin injections (MDI), diet plan, and frequent phone contact with a certified diabetes educator; Drug: Regular Insulin; Regular Insulin, IV, to maintain blood glucose in normoglycemic range (70-140) during metabolic study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glutathione Concentration	While at near normoglycemia	After 3-9 months of improved blood glucose control (HbA1c decrease of >0.5%)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Protein Bound 3-nitrotyrosine	Marker of oxidative stress	After 3-9 months of improved blood glucose control (HbA1c decrease of >0.5%)

Collaborators and Investigators

• Sponsor: Nemours Children's Clinic
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Dominique Darmaun, MD, PhD, Nemours Children's Clinic

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: March 6, 2009
• First Submitted That Met QC Criteria: March 6, 2009
• First Posted (Estimate): March 9, 2009

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Glutathione
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Insulin; Insulin, Globin Zinc; Antioxidants
• Other Study ID Numbers: JDRF 1-2006-627-B