Using an Artificial Pancreas System in Older Adult Type 1 Diabetes Mellitus Patients

The goals of this proposal are to implement a Close-Loop/Artificial Pancreas (CL/AP) system
in older patients with type 1 diabetes mellitus (T1DM) in order to reverse brain metabolic
adaptations and restore metabolic sensitivity, hypoglycemia awareness and appropriate
hormonal counterregulatory responses (CRR). For purposes of this study we are looking to
enroll aged T1DM subjects under insulin pump treatment.

Inclusion Criteria:

- Provide signed and dated informed consent form

- Male or female

- Age 50-75 years (at least 50% over the age of 65)

- T1DM (>20 years duration)

- C-peptide undetectable

- HbA1c of < 8%

- Insulin pump therapy

- History of frequent hypoglycemia with unawareness (defined as 2 or more episodes of
severe hypoglycemia within one year requiring assistance) and 2 or more glucose values
< 54 mg/dL during the week of Continuous Glucose Monitoring (CGM) (iPRO monitor,
Medtronic) prior to enrollment

- BMI <27 kg/m2

- Good general health as evidenced by medical history and blood screening

- Willing to comply with all study procedures and be available for the duration of the
study

- Willing to fast for a limited time period on the morning of a clamp study

Exclusion Criteria:

- Significant diabetic complications (untreated proliferative retinopathy, creatinine
≥1.5 mg/dl, urinary albumin levels 300 mg/day, autonomic neuropathy, painful
peripheral neuropathy)

- Significant alcohol intake and vegetarian diet since both are known to have an impact
on counterregulation and brain metabolism

- Any contraindications for MRI scanning, including presence of metallic implants or
claustrophobia.

- Heavy exercise on a regular basis (i.e. marathon runners)

- Known allergic reactions to components of the study product(s)

- Treatment with another investigational drug or other intervention

- Active infection including hepatitis C, hepatitis B, HIV

- Any past or current history of alcohol or substance abuse

- Psychiatric or neurological disorders under active treatment

- Baseline hemoglobin < 10.5 g/dL in females, or < 12.5 g/dL in males. Blood donation
within 30 days of the study

- History of coagulopathy or medical condition requiring long-term anticoagulant therapy
(low-dose aspirin treatment is allowed)

- Co-existing cardiac, liver, and kidney disease

- Abnormal liver function tests

- Women that are on oral contraceptives, post-menopausal, pregnant (as assessed by
pregnancy test that will be performed on female participants at reproductive age), or
lactating.

- Any medical condition or medication that, in the opinion of the investigators, will
interfere with the safe completion of the study or study outcomes