Mechanisms for Restoration of Hypoglycemia Awareness

Study Overview
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Brief Summary
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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
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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.

Official Title
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Mechanisms for Restoration of Hypoglycemia Awareness

Conditions
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Type1 Diabetes Mellitus

Intervention / Treatment
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* Device: Continuous Glucose Monitor (CGM)
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aim 3: Type 1 diabetes mellitus user unaware subjects 3 months<br>Continuous Glucose Monitor for 3 months duration | Device: Continuous Glucose Monitor (CGM)<br>* Continuous Glucose Monitor (CGM)<br>* Other names: Dexcom G6;Drug: Insulin<br>* standard insulin regimen<br>|
| Experimental: Aim 1: Impact of hypoglycemia on brain connectivity Type 1<br>Healthy controls, T1 aware, and T1 unawares | Drug: Insulin<br>* standard insulin regimen<br>|
| Experimental: Aim 2: Impact of hypoglycemia on brain glucose transports in Type 1<br>Healthy controls, T1 aware, and T1 unawares | Drug: Insulin<br>* standard insulin regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain glucose levels | Brain glucose will be lower and brain activation higher in those receiving continuous glucose monitor Rx. | 3 months |