Diabetes Mellitus, Type 1
Conditions
Keywords
Glutathione
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTAntioxidant supplement
1 capsule daily with dinner
OTHERDiabetes 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
DRUGRegular Insulin
Regular Insulin, IV, to maintain blood glucose in normoglycemic range (70-140) during metabolic study
Sponsors
Juvenile Diabetes Research Foundation
Nemours Children's Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glutathione Concentration | After 3-9 months of improved blood glucose control (HbA1c decrease of >0.5%) | While at near normoglycemia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Protein Bound 3-nitrotyrosine | After 3-9 months of improved blood glucose control (HbA1c decrease of >0.5%) | Marker of oxidative stress |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Antioxidant Supplement Vitamin C 250 mg; beta-carotene 6 mg; vitamin E 30 mg; selenium 100 mcg; zinc 20 mg
Antioxidant supplement: 1 capsule daily with dinner
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
Regular Insulin: Regular Insulin, IV, to maintain blood glucose in normoglycemic range (70-140) during metabolic study | 17 |
| Placebo Antioxidant supplement: 1 capsule daily with dinner
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
Regular Insulin: Regular Insulin, IV, to maintain blood glucose in normoglycemic range (70-140) during metabolic study | 15 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 3 | 5 |
Baseline characteristics
| Characteristic | Placebo | Antioxidant Supplement | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 15 Participants | 17 Participants | 32 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 15.8 years STANDARD_DEVIATION 2.6 | 15.7 years STANDARD_DEVIATION 2.3 | 15.8 years STANDARD_DEVIATION 2.4 |
| Region of Enrollment United States | 15 participants | 17 participants | 32 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 12 Participants | 14 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 15 |
| other Total, other adverse events | 0 / 17 | 0 / 15 |
| serious Total, serious adverse events | 0 / 17 | 0 / 15 |
Outcome results
Primary
Glutathione Concentration
While at near normoglycemia
Time frame: After 3-9 months of improved blood glucose control (HbA1c decrease of >0.5%)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antioxidant Supplement | Glutathione Concentration | 706 umol/L | Standard Deviation 236 |
| Placebo | Glutathione Concentration | 734 umol/L | Standard Deviation 215 |
Secondary
Plasma Protein Bound 3-nitrotyrosine
Marker of oxidative stress
Time frame: After 3-9 months of improved blood glucose control (HbA1c decrease of >0.5%)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Antioxidant Supplement | Plasma Protein Bound 3-nitrotyrosine | 4.26 ng/mL |
| Placebo | Plasma Protein Bound 3-nitrotyrosine | 7.13 ng/mL |