Type1 Diabetes Mellitus
Conditions
Brief summary
To assess if using the hypoglycemic clamp and functional magnetic resonance imaging (fMRI) scanning in hypoglycemia unaware and aware T1DM patients and healthy controls have showed distinct differences in patterns of brain responses. In particular, T1DM patients who are aware of hypoglycemia (T1DM-Aware) have greater activity in sensory integration brain regions (e.g. parietal lobe and caudate nucleus) in response to hypoglycemia, whereas hypoglycemia unaware T1DM patients (T1DM-Unaware) show no detectable changes in brain reward regions during hypoglycemia.
Detailed description
To assess the following: 1) if these differences are driven purely by recurrent hypoglycemia or by other closely linked factors (e.g. glycemic variability); 2) the molecular and metabolic mechanisms by which unawareness leads to the suppression of central nervous system (CNS) activity in the context of hypoglycemia; and 3) whether hypoglycemia avoidance using continuous glucose monitor restores central nervous system (CNS) activation and metabolism toward normal levels and offers a therapeutic approach to more effectively combat neurocognitive dysfunction associated with intensive treatment of T1DM patients.
Interventions
DEVICEContinuous Glucose Monitor (CGM)
Continuous Glucose Monitor (CGM)
DRUGInsulin
standard insulin regimen
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Ages \> 18 years * Healthy, non-diabetic control or T1DM * BMI \> 18.0
Exclusion criteria
* Creatinine \> 1.5 mg/dL * Hct \< 35% for females, \< 39% for males * ALT \> 2.5 X ULN * untreated thyroid disease * uncontrolled hypertension * neurologic disorders * untreated depression or change in antidepressant regimen in last 3 months * use of any anxiolytic medications (benzodiazepine) or antipsychotic medications * greater than 5% change in weight in last 3 months * malignancy * current or recent steroid use in last 3 months * illicit drug use * significant complications related to diabetes (peripheral neuropathy, proliferative retinopathy) * inability to enter MRI (per standard MRI safety guidelines) * for women: pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Glucose Levels | 3 months | Regional quantification of brain glucose levels with MRS (CMRgl) will be used to measure group differences. |
Countries
United States
Participant flow
Pre-assignment details
15 participants withdrew and 7 had IV issues
Participants by arm
| Arm | Count |
|---|---|
| Healthy Controls Healthy controls Insulin: standard insulin regimen | 23 |
| Type 1 (T1) Diabetics T1 aware, and T1 unawares
Insulin: standard insulin regimen | 32 |
| Total | 55 |
Baseline characteristics
| Characteristic | Healthy Controls | Type 1 (T1) Diabetics | Total |
|---|---|---|---|
| Age, Continuous | 29.6 years STANDARD_DEVIATION 7.4 | 34.5 years STANDARD_DEVIATION 11.6 | 32.6 years STANDARD_DEVIATION 10.3 |
| Diastolic Blood Pressure | 73.3 mmHg STANDARD_DEVIATION 11.7 | 75.5 mmHg STANDARD_DEVIATION 8.8 | 74.5 mmHg STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 30 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 28 Participants | 42 Participants |
| Region of Enrollment United States | 23 participants | 32 participants | 55 participants |
| Sex: Female, Male Female | 16 Participants | 17 Participants | 33 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 22 Participants |
| Systolic Blood Pressure | 115.8 mmHg STANDARD_DEVIATION 13.7 | 120.5 mmHg STANDARD_DEVIATION 12.5 | 117.1 mmHg STANDARD_DEVIATION 12.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 21 |
| other Total, other adverse events | 0 / 12 | 0 / 21 |
| serious Total, serious adverse events | 0 / 12 | 0 / 21 |
Outcome results
Primary
Brain Glucose Levels
Regional quantification of brain glucose levels with MRS (CMRgl) will be used to measure group differences.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Brain Glucose Levels | 2.45 Mmol/L | Standard Deviation 0.6 |
| Type 1 (T1) Diabetics | Brain Glucose Levels | 2.16 Mmol/L | Standard Deviation 5 |
p-value: 0.907ANOVA