Insulin Sensitivity, Impaired Counterregulation, and Glucose Variability
Insulin Sensitivity, Impaired Counterregulation, and Glucose Variability
This protocol will investigate physiological parameters including insulin sensitivity and
 counterregulatory function using a mixed meal test and induced hypoglycemia in subjects with
 type I diabetes.
The principal idea of the proposed research is: in order to be successful, closed-loop
 control of glucose in diabetes must adapt to individual physiologic characteristics and to
 the behavioral profile of each person. We propose to build a system that will use observers
 of patients' behavior and metabolic state and control modules that are responsible for
 insulin delivery and hypoglycemia prevention. In this phase of the project, we will
 investigate relationships of insulin sensitivity and impaired counterregulation with blood
 glucose variability, aiming to develop algorithmic physiology observers, which will track
 specific parameters of glucose variability and recurrent hypoglycemia as markers of change in
 a person's insulin sensitivity and counterregulatory ability.
Inclusion Criteria:

 -  Type I diabetes mellitus (TIDM) (as defined by the American Diabetes Association
 criteria or judgment of a physician) for at least two years prior to the enrollment in
 the study.

 -  Use of an insulin pump to treat their diabetes for at least six months prior to the
 study.

 -  Ability to use a bolus calculator function with the current insulin pump with
 pre-defined parameters for glucose goal, carbohydrate ratio, and insulin sensitivity
 factor.

 -  Age 21 - 64 years. Adults age 65 and over are likely to have medical exclusions for
 the follow-up Phase 2 study, which involves induced hypoglycemia.

 -  Completed Phase 1 of the Institutional Review Board (IRB) #14956 "Development of a
 Behavioral Observer for Type 1 Diabetes Mellitus"

 -  Willingness to use lispro (Humalog) insulin two days prior to and during inpatient
 admission.

 -  Willingness to perform Self-Monitoring Blood Glucose (SMBG) 4 times per day at times
 before meals and bedtime.

 -  Demonstration of proper mental status and cognition for completion of the study.

 Exclusion Criteria:

 -  Pregnancy

 -  Psychiatric disorders that would interfere with study tasks (e.g. mental retardation,
 substance abuse)

 -  History of a systemic deep tissue infection with methicillin-resistant staph aureus or
 Candida albicans

 -  Known bleeding diathesis or dyscrasia

 -  Active enrollment in another clinical trial

 -  Medical condition that would make operating an insulin pump difficult (e.g. blindness,
 severe arthritis, extensive scar tissue at sites where devices are inserted).

 -  Anemia (hematocrit <36% [females], <38% [males]),

 -  Allergy or adverse reaction to lispro (Humalog) insulin

 -  Conditions which may increase the risk of induced hypoglycemia such as symptomatic
 heart disease, congestive heart failure, history of a cerebrovascular event, atrial
 fibrillation, renal insufficiency (creatinine >1.5) or uncontrolled hypertension
 (resting blood pressure >140/90).