Exercise Detection Study

The artificial pancreas, a device used for automatic delivery of insulin and glucagon
subcutaneously to subjects with type 1 diabetes, is paving the way to revolutionize the
management of this disease. Already, the benefit of improved glycemic control compared to
current open-loop pump therapy has been demonstrated in several trials. The investigator's
group has shown that artificial pancreas algorithm dual hormone system effectively manages
blood glucose in a clinic setting and the investigators have specifically shown great
progress using glucagon to reduce hypoglycemic episodes outside of exercise. The
investigators most recent inpatient study, as yet unpublished, shows that adjusting insulin
and glucagon delivery during closed loop treatment, after announcing exercise, effectively
reduces mean time below a glucose level of 70 mg/dl when compared to closed loop control
without adjustments. The investigators utilized initial open-loop data from this study to
help devise dosing changes for the artificial pancreas algorithm.

In order to prepare for a future home study, the ability to detect, grade, and classify
physical activity so as to appropriately adjust system parameters is vital in helping to
prevent exercise induced hypoglycemia in the home setting. Currently, our closed-loop system
transmits heart rate and accelerometry outputs from a Zephyrlife BioPatch monitoring device
to a Nexus 5 smart phone master controller via Bluetooth. The algorithm then converts the
heart rate and accelerometry data into modified estimated energy expenditure - accounting
for age, weight, height, sex, resting and sitting heart rates - to determine if exercise is
present. However, further data collection is needed to hone the specificity and sensitivity
of the detection algorithm to account for a wide variety of subject characteristics and
activities.

This study is designed to collect 3-axis accelerometry data and heart rate data during a
variety of different home activities, as well as during formal exercise, both aerobic
exercise (on a calibrated treadmill) and resistance exercise (straight-leg raises or
equivalent), in healthy subjects as well as subjects with type 1 diabetes. Optionally VO2
data from a portable VO2 mask will be obtained. The data collected will be used to further
enhance our algorithm that, in future closed-loop studies, will detect exercise and
automatically trigger algorithmic adjustments to reduce exercise-related hypoglycemia during
and after exercise in individuals with type 1 diabetes.

TYPE 1 DIABETIC SUBJECT CRITERIA

Inclusion criteria:

1. Male or female subjects 21 to 45 years of age with a diagnosis of T1D for at least 6
months on an insulin pump.

2. Physically active on a regular basis, i.e. at least 3 days of scheduled physical
activity per week and willing to perform approximately 60 minutes of exercise (as
determined by the investigator after reviewing the subjects activity level).

3. Willingness to follow all study procedures.

4. Willingness to sign informed consent and HIPAA documents.

Exclusion criteria:

a. Pregnancy or Lactation: i. For women of childbearing potential, there is a requirement
for a negative urine pregnancy test. b. Any cardiovascular disease, defined as a
clinically significant EKG abnormality at the time of screening or any history of: stroke,
heart failure, myocardial infarction, angina pectoris, or coronary arterial bypass graft
or angioplasty. Diagnosis of 2nd or 3rd degree heart block or any non-physiological
arrhythmia judged by the investigator to be exclusionary. c. Renal insufficiency (GFR < 60
ml/min, using the MDRD equation as report by the OHSU laboratory). d. Hematocrit of less
than or equal to 34%. e. History of severe hypoglycemia during the past 12 months prior to
screening visit or hypoglycemia unawareness as judged by the investigator. f. Adrenal
insufficiency. g. Any active infection. h. Known or suspected abuse of alcohol, narcotics,
or illicit drugs (except marijuana use).

i. Seizure disorder. j. Active foot ulceration. k. Severe peripheral arterial disease
characterized by ischemic rest pain or severe claudication. l. Major surgical operation
within 30 days prior to screening. m. Use of an investigational drug within 30 days prior
to screening. n. Chronic usage of any immunosuppressive medication (such as cyclosporine,
azathioprine, sirolimus, or tacrolimus). o. Bleeding disorder, treatment with warfarin, or
platelet count below 50,000. p. Current administration of oral or parenteral
corticosteroids. q. Any life threatening disease, including malignant neoplasms and
medical history of malignant neoplasms within the past 5 years prior to screening (except
basal and squamous cell skin cancer). r. Any concurrent illness, other than diabetes, that
is not controlled by a stable therapeutic regimen. s. Beta blockers or non-dihydropyridine
calcium channel blockers. t. A positive response to any of the questions from the Physical
Activity Readiness Questionnaire, see Appendix A. u. Any chest discomfort with physical
activity, including pain or pressure, or other types of discomfort. v. Any clinically
significant disease or disorder which in the opinion of the Investigator may jeopardize
the subject's safety or compliance with the protocol.

HEALTHY SUBJECT CRITERIA

Inclusion Criteria:

1. Male or female subjects 21 to 45 years of age.

2. Physically active on a regular basis, i.e. at least 3 days of scheduled physical
activity per week and willing to perform approximately 60 minutes of exercise (as
determined by the investigator after reviewing the subjects activity level).

3. Willingness to follow all study procedures.

4. Willingness to sign informed consent and HIPAA documents.

Exclusion criteria:

1. Pregnancy or Lactation: For women of childbearing potential, there is a requirement
for a negative urine pregnancy test.

2. Any history or evidence of renal insufficiency, adrenal insufficiency, liver disease
or anemia.

3. A history of cerebrovascular disease or coronary artery disease (or angina)
regardless of the time since occurrence.

4. Congestive heart failure, New York Heart Association (NYHA) any class.

5. Diagnosis of 1st, 2nd or 3rd degree heart block or any arrhythmia judged by the
investigator to be exclusionary.

6. Any condition which, in the opinion of the investigator, makes it difficult to engage
in vigorous physical activity.

7. Any active infection.

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

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

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

11. Major surgical operation within 30 days prior to screening.

12. Seizure disorder.

13. Bleeding disorder, or treatment with warfarin.

14. Use of any chronic medications.

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

16. Any reason the principal investigator deems exclusionary.