Effect of Hypoglycemia on Sleep

The study duration is 4 weeks long, during which subjects will undergo a 1 week run-in
period followed by 3 randomized weeks of observational study. During the 1 week run-in
period, subjects will familiarize themselves with the CGM and the other data collection
procedures. Following the run-in week, the subject will be randomized to a specific order of
observation weeks. The three observation weeks are a resistance training week, an aerobic
exercise week and a control week with no explicit exercise. During the observation weeks,
there will be 4 interventions planned, two during both the aerobic exercise and the
resistance training week. See Schematic below for details. During both the aerobic exercise
week intervention visits, subjects will exercise for ~45 minutes on a treadmill and during
the resistance training week, subjects will perform strength training exercises for 1-3 sets
per exercise at a weight that can be lifted for 8-12 repetitions (~60-80% of 1-repetition
max). The duration of the resistance training period is expected to be ~45min. Subjects will
continue to perform daily activities during each of the weeks.

During each week, the subject will wear one subcutaneous DexcomTM G4 or DexcomTM G4 Share
continuous glucose monitoring (CGM) system, one activity monitor- ActiGraph wGT3X-BT or
ActiGraph GT9X, one insulin pump (subject's own pump) and one Samsung Galaxy S4 phone loaded
with two applications- meal memory and moves. The CGM system will provide sensed glucose
data every 5 minutes. The CGM data will be blinded to the patient to prevent any abrupt
changes in behavior. The accuracy of the sensed data will be obtained by reference
measurements of capillary blood glucose. The activity monitor will be secured on the
dominant wrist and uses an accelerometer to collect movement data at a high frequency
(80Hz). The activity monitor measures both motion and ambient light, this data would be used
to determine the various sleep quality measures. The subject's insulin dosage information
from the pump will be downloaded for data analysis purposes. The subject's daily meal intake
(photographic log and note diary) and daily movement pattern information will be downloaded
from the phone. During the 4 exercise intervention visits, subject's heart rate,
accelerometry information from the torso and oxygen consumption measured breath by breath
may be collected for data analysis purposes.

Inclusion Criteria:

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

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

3. Physically active on a regular basis, i.e. at least 3 days of physical activity per
week.

4. Physically willing and able to perform 45 min of exercise (as determined by the
investigator after reviewing the subjects activity level)

5. Current use of an insulin pump.

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

7. Willingness to sign informed consent and HIPAA documents.

Exclusion Criteria:

1. Female of childbearing potential who is pregnant or intending to become pregnant or
breast-feeding, or is not using adequate contraceptive methods. Acceptable
contraception includes birth control pill / patch / vaginal ring, Depo-Provera,
Norplant, an intrauterine device (IUD), the double barrier method (the woman uses a
diaphragm and spermicide and the man uses a condom), or abstinence.

2. 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.

3. Renal insufficiency (GFR < 60 ml/min, using the MDRD equation as report by the OHSU
laboratory).

4. Impaired liver function, defined as AST or ALT ≥2.5 times upper limit of normal,
according to OHSU laboratory reference ranges.

5. Hematocrit of less than or equal to 34%.

6. History of severe hypoglycemia during the past 12 months prior to screening visit or
hypoglycemia unawareness as judged by the investigator.

7. Adrenal insufficiency.

8. Any active infection.

9. Known or suspected abuse of alcohol, narcotics, or illicit drugs (except marijuana
use).

10. Seizure disorder.

11. Active foot ulceration.

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

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

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

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

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

17. Insulin resistance requiring more than 200 units per day.

18. Need for uninterrupted treatment with acetaminophen.

19. Current administration of oral or parenteral corticosteroids.

20. 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).

21. C peptide level of ≥0.5 ng/ml

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

23. Beta blockers or non-dihydropyridine calcium channel blockers.

24. A positive response to any of the questions from the Physical Activity Readiness
Questionnaire.

25. Any chest discomfort with physical activity, including pain or pressure, or other
types of discomfort.

26. Any clinically significant disease or disorder which in the opinion of the
Investigator may jeopardize the subject's safety or compliance with the protocol.