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.

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.

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

Baseline characteristics were collected for all enrolled participants

3 months

blinded