Effect of Gain on Closed-Loop Insulin

There have been significant advances in diabetes management technology, including more
sophisticated insulin pumps and more accurate real-time continuous glucose monitors. The next
technological development is widely thought to be the introduction of an algorithm linking
the pump and sensor to form a closed-loop insulin delivery system. The algorithm used for
this purpose needs to be robust to changes in an individual's insulin sensitivity, and the
sensor's sensitivity to glucose. Insulin sensitivity (how much the patient's glucose level
changes in response to a change in insulin delivery) and algorithm gain (how much insulin is
delivered in response to a change in glucose) determine the systems overall closed-loop gain.
Ideally, the overall gain can be set to achieve the lowest possible peak postprandial glucose
response without postprandial hypoglycemia. However, if the algorithm's gain is set to a
fixed value and the subject's insulin sensitivity changes, the overall-gain will change. Some
degradation in closed-loop performance might be acceptable during periods whenever the
subject's insulin sensitivity is low (i.e., the subject is insulin resistant) and the risk of
hypoglycemia may actually be reduced. However, if the subject becomes more sensitive the
system may become less stable and the risk of postprandial hypoglycemia may increase. In
addition to changes in insulin sensitivity, glucose sensors will sometimes over- or
under-read blood glucose as sensor sensitivity increases or decreases. This will result in a
change in the closed-loop algorithm's effective target. The purpose of this study is to
evaluate the ability of an advanced Physiologic Insulin Delivery algorithm to achieve an
acceptable breakfast response as the gain and effective target glucose level changes.
Specifically:

1. to assess the fasting glucose levels achieved as the overall closed-loop gain and
effective target is increased or decreased, and

2. determine the system's ability to produce an acceptable breakfast meal response under
these conditions

Inclusion Criteria:

- Type 1 diabetes for > 3 years

- Manage diabetes using a continuous glucose monitor and continuous subcutaneous insulin
infusion pump

- Non obese (BMI < 30)

- Aged 18 - 75 years old

- HbA1c < 8 %

Exclusion Criteria:

- renal or hepatic failure

- cancer or lymphoma

- Malabsorption or malnourishment

- Hypercortisolism

- Alcoholism or drug abuse

- Anemia (hematocrit < 36 in females and <40 in males)

- Eating disorder

- Dietary restrictions

- Acetaminophen allergy

- Chronic acetaminophen use

- Glucocorticoid therapy

- History of gastroparesis

- Use of Beta blockers