A Dual Hormone Artificial Pancreas System Successfully Tested in Two-Day Hospital-Based Studies

Artificial pancreas systems will enable people with T1D to achieve tighter blood glucose control avoiding both highs and dangerous lows, thereby significantly reducing the risk of the disease’s devastating complications. In addition to insulin-only approaches, researchers are developing and testing artificial pancreas systems that utilize glucagon, a hormone that is produced in the body that naturally raises blood glucose levels but is not regulated properly in people with T1D. Currently glucagon is used in hypoglycemia rescue kits to rapidly raise blood sugar during severe hypoglycemia. In these studies, glucagon is used to more rapidly counteract falls in blood glucose than only by slowing or switching off insulin delivery. In this research, Dr. Edward Damiano’s team at Boston University and collaborators at Massachusetts General Hospital conducted in-hospital studies to determine whether safe and effective blood sugar control could be achieved in T1D using an automated artificial pancreas system that subcutaneously dosed both glucagon and insulin in response to readings from a continuous glucose monitor. Six subjects with T1D were enrolled in two experiments each lasting more than two days and included six high-carbohydrate meals and exercise as challenges to blood sugar control. Subjects were given a partial bolus of insulin at the beginning of each meal and their blood sugars were measured every 15 minutes. The average blood sugar concentration in the study was 158 mg/dL, with 68% of the values in the range of 70–180 mg/dL. There were no significant differences in average blood sugar concentrations between larger and smaller pre-meal insulin boluses suggesting that while it will be necessary to bolus for meals with this system, the doses may not need to be carefully calculated. Low blood sugar conditions (blood sugar below 70 mg/dL) were rare, with only eight incidents during 576 hours of system control (0.7% of total time). During 192 hours of nighttime control, the average blood sugar level was 123 mg/dL, with 93% of blood sugar values in the range of 70–180 mg/dL with only one episode of mild low blood sugar where the blood glucose decreased to 62 mg/dL. These promising results showed excellent blood sugar control with minimal hypoglycemia over two days of bihormonal closed loop control despite high-carbohydrate meals and exercise and strongly justify further testing of a wearable version of the system under real-life conditions.

Ramifications for Individuals with T1D:

JDRF’s Artificial Pancreas Consortium is comprised of top diabetes clinician researchers and is supporting multiple approaches to a bihormonal artificial pancreas system. Both Dr. Edward Damiano and Dr. Ken Ward at Oregon Health Sciences University are separately developing and testing bihormonal approaches for closed loop artificial pancreas systems using glucagon as the second hormonal drug. Such systems hold the promise of more closely simulating natural control of blood sugar levels given the complementary actions of these two hormones. Dr. Damiano’s next steps are to conduct longer, more ambulatory studies in the hospital setting followed by outpatient studies.

JDRF Involvement:

JDRF partially funded this research through a grant to Dr. Ed Damiano at Boston University. Dr. Damiano is a member of the JDRF Artificial Pancreas Consortium.

Investigators and Institutions:

Steven Russell1, Firas El-Khatib2, David Nathan1, Kendra Maygar1, John Jiang2 and Edward Damiano1, 1Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts and 2Department of Biomedical Engineering, Boston University, Boston Massachusetts

Reference:

Russell SJ, El-Khatib FH, Nathan DM, Magyar KL, Jiang J, Damiano ER. 2012. Blood Glucose Control in Type 1 Diabetes With a Bihormonal Bionic Endocrine Pancreas. Diabetes Care 35 (11): 2148-2155.