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.

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.

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