Artificial Pancreas Control System in an Inpatient Setting

The objective of the current human study is to verify the components of the Artificial
Pancreas Control system during an inpatient study. This master controller software is
designed to be used in conjunction with two subcutaneous continuous glucose monitoring
systems to regulate blood glucose levels as well as two Omnipod pumps, one for administering
insulin and one for administering glucagon. The sensors communicate wirelessly with two
sensor receivers which will be interfaced with the APC by wireless USB connection. The
insulin and glucagon pumps will be controlled by the APC through a wireless USB connection.
The algorithm included in the APC is an automated version of the Adaptive Proportional
Derivative (APD) insulin and glucagon control algorithm, which was previously studied as an
investigational device. The APD has been studied in vivo (in 28 experiments, each 33 hr in
length, with manual adjustment of pumps) and no serious adverse effects were noted. Manual
input of the glucose sensor data and insulin/glucagon infusion rates will no longer be
necessary. The APC will be tested in vivo during 28 hour experiments in an inpatient
setting in preparation for outpatient testing.

Inclusion Criteria:

- Diagnosis of type 1 diabetes mellitus for at least 1 year.

- Male or female subjects 21 to 65 years of age.

- Current use of an insulin pump.

- Willingness to follow all study procedures, including attending all clinic visits.

- Willingness to sign informed consent and HIPAA documents.

Exclusion Criteria:

- Pregnancy or Lactation: For women of childbearing potential: there is a requirement
for a negative urine pregnancy test and for agreement to use contraception during the
study and for at least 1 month after participating in the study. Acceptable
contraception includes birth control pill / patch / vaginal ring, Depo-Provera,
Norplant, an IUD, the double barrier method (the woman uses a diaphragm and
spermicide and the man uses a condom), or abstinence.

- Renal insufficiency (serum creatinine of 2.0 mg/dL or greater).

- Serum ALT or AST equal to or greater than 3 times the upper limit of normal; hepatic
synthetic insufficiency as defined as a serum albumin of less than 3.3 g/dL; or serum
bilirubin of over 2.

- Adrenal insufficiency

- Hematocrit of less than or equal to 34%.

- A history of cerebrovascular disease or coronary artery disease regardless of the
time since occurrence.

- Congestive heart failure, NYHA class III or IV.

- Diagnosis of 2nd or 3rd degree heart block or any arrhythmia judged by the
investigator to be exclusionary.

- Any active infection.

- Visual impairment preventing reading of glucose meter values or continuous glucose
monitoring device.

- Physical impairment impeding the ability to use a glucose meter or glucose monitoring
device.

- Active foot ulceration.

- Severe peripheral arterial disease characterized by ischemic rest pain or severe
claudication.

- Active alcohol abuse, substance abuse, or severe mental illness (as judged by the
principal investigator).

- Active malignancy, except basal cell or squamous cell skin cancers.

- Major surgical operation within 30 days prior to screening.

- Seizure disorder.

- Chronic usage of any immunosuppressive medication (such as cyclosporine,
azathioprine, sirolimus, or tacrolimus).

- Current administration of oral or parenteral corticosteroids.

- Use of an investigational drug within 30 days prior to screening.

- Bleeding disorder, treatment with warfarin, or platelet count below 50,000.

- Allergy to aspart insulin.

- Allergy to glucagon.

- Past history of pheochromocytoma or a family history of MEN 2, neurofibromatosis, or
von Hippel-Lindau disease.

- Insulin resistance requiring more than 200 units per day.

- Need for uninterrupted treatment of acetaminophen.

- Intolerance of mild hypoglycemia (glucose 60-70 mg/dl).

- History of hypoglycemic unawareness.

- Insulin antibody level of ≥ 100 µUnits/ml.

- C peptide level of ≥0.5 ng/ml.

- Any concurrent illness, other than diabetes, that is not controlled by a stable
therapeutic regimen.

- Any reason the principal investigator deems exclusionary