Integration of Continuous Glucose Monitoring Into a BiHormonal Closed-Loop Artificial Pancreas

To test the safety and efficacy of our control system in the bi-hormonal configuration in
regulating BG in adults (18 years of age or older) and in children (12-17 years of age) with
type 1 diabetes based on interstitial-fluid (ISF) glucose data from a CGM. Experiments will
be 51 hours in length incorporating 6 meals and two (night) sleep periods. In order to
evaluate the effect of exercise on BG control, the last 48 hours of the experiment will be
divided into two 24 hour blocks, the second of which will contain a period of structured
exercise near the beginning of the block.

Inclusion Criteria:

- Age 12 years or older with clinical type 1 diabetes for at least one year

- Weight > 41 kg

- Otherwise healthy (mild chronic disease allowed if well controlled)

- Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting
insulins

- Body mass index (BMI) between 20 and 35 for subjects >18 years of age or BMI between
the 5th and 95th percentile for age for subjects < 18 years of age

- Total daily dose (TDD) of insulin that is < 1 U/kg

- Stimulated C-peptide < 0.1 nmol/L at 90 minutes after liquid mixed meal by DCCT
protocol

- Hemoglobin A1c <= 9%

- Prescription medication regimen stable for 1 month

Exclusion Criteria:

- Unable to provide informed consent for subjects > 18 years of age or unable to provide
assent if < 18 years of age

- Unable to comply with study procedures

- Current participation in another diabetes-related clinical trial other than one that
is primarily observational in nature. Potential subjects enrolled in trials of passive
monitoring equipment are not excluded.

- Anemia (HCT less than normal for age and sex)

- Alanine aminotransferase > 3 fold above upper limit of normal

- Untreated or inadequately treated hyperthyroidism or hypothyroidism

- Pregnancy

- Renal insufficiency (creatinine clearance ≤ 50 ml/min)

- Any known history of coronary artery disease

- Abnormal EKG including, but not limited to evidence of active ischemia, prior
myocardial infarction, proximal LAD critical stenosis (Wellen's sign), arrhythmia,
tachycardia, and prolonged QT interval (> 440 ms)

- Congestive heart failure

- History of TIA or stroke

- Acute illness or exacerbation of chronic illness

- History of seizures

- History of pheochromocytoma (fractionated metanephrines will be tested in patients
with history suggestive of pheochromocytoma)

- History of adrenal disease or tumor

- History of pancreatic tumor, including insulinoma

- History of impaired gastric motility or gastroparesis requiring pharmacological or
surgical treatment

- Current alcohol abuse (intake averaging > 3 drinks daily in last 30 days) or substance
abuse (any use within the last 6 months of controlled substances without a
prescription)

- Untreated or inadequately treated mental illness (indicators would include symptoms
such as psychosis, hallucinations, mania, and any psychiatric hospitalization in the
last year)

- Impaired cognition or altered mental status.

- Hypertension (blood pressure > 140/90 or > 95% for age, height and weight in subjects
< 18 years of age) at the time of screening

- Use of medications that reduce gastric motility (e.g. narcotics, anti-spasmodics,
anticholinergics).

- Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be
susceptible to RF interference

- Use non-insulin, injectable anti-diabetic medications

- History of adverse reaction to glucagon (including allergy) besides nausea and
vomiting.

- Established history of latex, adhesive, or tape allergy

- Inadequate venous access

- History of allergy to aspirin or any history of aspirin intolerance, including Reye
syndrome, or gastric ulcer or bleeding associated with salicylates

- Blood dyscrasia or bleeding diathesis, such as hemophilia, Von Willebrands disorder,
and idiopathic thrombocytopenic purpura (ITP)

- Peptic ulcer

- Unable to perform 30 minutes of moderate exercise on a treadmill or exercise bicycle

- Unable or unwilling to discontinue dietary supplements for at least 2 weeks prior to
each CRC admission

- History of celiac disease