Diabetes Mellitus, Type 1
Conditions
Keywords
Glutathione
Brief summary
Glutathione is normally present at high (millimolar) levels in blood and plays an important role in the body's defense against oxidative stress, that is, against the damage caused to the body by 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 blood depends on the balance between its rate of synthesis and its rate of use. In earlier studies, the investigators found that in poorly controlled diabetic teenagers, glutathione was low, not because its production was decreased, but because it was used at an excessive rate. In this study, the investigators want to determine how short-term changes in blood sugar levels affect glutathione levels. This will help improve our understanding of how diabetes affects metabolism.
Detailed description
Adolescents with uncomplicated T1D will receive two, 5-hour infusions of deuterium-labeled cysteine on 2 separate days, a few weeks apart, while blood glucose will be maintained, using intravenous insulin infusion: * in the hyper-glycemic range (200-250 mg/dL) on one study day, and * near normoglycemia (80-140 mg/dL) on the other study day. The order of the study days will be randomized. We will determine whether the level of blood glucose at the time of study affects blood glutathione concentration, and, if so, whether this is associated with changes in the fractional rate of glutathione synthesis, as determined from the incorporation of labeled cysteine into blood glutathione over the course of the 5-hr infusion of labeled cysteine.
Interventions
OTHERCysteine isotope infusion at normoglycemia vs hyperglycemia
L-\[3,3-2H2\]cysteine
DRUGRegular Insulin
Regular insulin, IV, as needed to maintain blood glucose in near-normoglycemic range (80-140 mg/dL) or hyperglycemic range (200-250 mg/mL) during metabolic studies
Sponsors
Juvenile Diabetes Research Foundation
Nemours Children's Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Type 1 diabetes, using usual criteria such as: glycosuria, hyperglycemia prior to treatment * BMI \<25 kg/m2 * Age 14-18 * 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 | Up to 30 minutes post- 5 hour infusion on Day 1 (First Intervention) and up to 30 minutes post- 5 hour infusion on Day 14 (Second Intervention) | umol/L |
Countries
United States
Participant flow
Pre-assignment details
Each of the 10 Subjects received two 5-hour intravenous infusions of L-\[3,3-2H2\]cysteine in the postabsorptive state on 2 separate days after blood glucose had been maintained overnight at normoglycemia or hyperglycemia, using intravenous insulin infusion. The order of the normo- and hyper-glycemia study days was randomized.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Enrolled Adolescents with Type 1 Diabetes | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | All Subjects Enrolled |
|---|---|
| Age, Categorical <=18 years | 10 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 16.9 years STANDARD_DEVIATION 1.5 |
| HbA1C | 9.2 percent of total hemoglobin STANDARD_DEVIATION 0.5 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Glutathione Concentration
umol/L
Time frame: Up to 30 minutes post- 5 hour infusion on Day 1 (First Intervention) and up to 30 minutes post- 5 hour infusion on Day 14 (Second Intervention)
Population: Each of the 10 Subjects received two 5-hour intravenous infusions of L-\[3,3-2H2\]cysteine in the postabsorptive state on 2 separate days after blood glucose had been maintained overnight at normoglycemia or hyperglycemia, using intravenous insulin infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normoglycemia (80-140 mg/dL) | Glutathione Concentration | 541 umol/L | Standard Error 232 |
| Hyperglycemia (200-250 mg/dL) | Glutathione Concentration | 551 umol/L | Standard Error 169 |