On April 9 and 10, 2013, dozens of scientists, engineers, and clinicians from North America, Europe, and the Middle East gathered on the NIH campus with the goal of improving the health and quality of life of people with diabetes. They were participants in the “Workshop on Innovation Towards an Artiicial Pancreas,” a forum on research and opportunities
to accelerate the development and delivery of a promising technological approach to treatment and management of diabetes: a wearable, automated artiicial pancreas. Organized by the NIDDK, the lead NIH Institute for artiicial pancreas research; the U.S. Food and Drug Administration (FDA), the federal agency regulating medical devices; and the leading
health advocacy group for people with type 1 diabetes, JDRF, this workshop represented just one of the latest in a continuing series of collaborative efforts that are helping to make the artiicial pancreas a reality.
Why an Artiicial Pancreas?
Both type 1 and type 2 diabetes cause the levels of glucose, or sugar, in the blood to rise above a normal, healthy range. When blood glucose levels are not well controlled, a person with diabetes is at much greater risk for developing devastating health complications, including blindness, kidney disease and kidney failure, nerve problems, and cardiovascular disease. These complications exact a heavy toll on both individuals and the health care system in terms of health and health care costs. Thus, inding ways to help people with diabetes optimize control of their blood glucose
levels is a critical goal for research on diabetes treatment and management.
For people with type 1 diabetes, controlling blood glucose levels is especially challenging. Type 1 diabetes destroys the insulin-producing beta ( β) cells of the pancreas. Without β cells, the pancreas is unable to sense rising glucose levels and respond with secretion of insulin, the hormone that enables the body to absorb glucose—the main source
of energy derived from digestion of food—from the bloodstream. To try and keep blood glucose levels within a healthy range, people with type 1 diabetes must measure glucose levels multiple times daily and, based on complex calculations, administer insulin via injection or a pump. While recent advances in technology such as continuous glucose monitors (CGMs) and “smart” insulin pumps that can help calculate insulin doses have helped many patients,
recapitulating the dynamic control of blood glucose levels imposed by the β cells of the pancreas is still impossible with current methods. Also, whereas a healthy pancreas has biological safeguards to help prevent blood glucose from dropping too low as well as rising too high, insulin therapy brings with it the risk of potentially life-threatening episodes of low blood glucose, or hypoglycemia, especially at night. Thus, researchers have been working intensively to advance
technology that can replace the exquisite control of blood glucose by the pancreas, hoping to achieve an “artificial pancreas” that automatically closes the loop between glucose sensing and delivery of appropriate amounts of insulin, while also preventing hypoglycemia and imposing minimal burden on the user.
Essential components of an artificial pancreas are:
- A glucose-sensing component (sensor) that measures blood glucose levels and sends information to a computer;
- An insulin delivery device, such as an insulin pump; and
- A computer that calculates the amount of insulin needed and thereby “closes the loop” between glucose sensing and insulin delivery.
Working Together To Advance the Field
The design of any system capable of achieving what is expected of an artiicial pancreas is complex, and raises novel scientiic, clinical, and regulatory challenges. Thus, the NIDDK is working with the FDA and JDRF to help overcome these challenges so that safe and effective artiicial pancreas systems can be developed and moved swiftly to market. For example, following a joint workshop on the artiicial pancreas organized by the NIDDK, the FDA, and JDRF in 2005,
the FDA in 2006 identiied “Accelerating the Availability of the Artiicial Pancreas” as one of its “critical path” initiatives—FDA’s strategy to drive innovation in the scientiic processes through which medical products are developed, evaluated, and manufactured. Then, in 2007, the FDA partnered with the NIDDK and other NIH Institutes to develop a working group of federal scientists, clinicians, and regulatory experts who would work together and with stakeholders, such as JDRF,
academic researchers, and industry, to ind ways to accelerate and optimize research and development efforts toward an artiicial pancreas. This Interagency Artiicial Pancreas Working Group meets regularly to discuss research and regulatory issues surrounding this new technology, and has been instrumental in promoting the ield, including contributing to the
development and release of the FDA comprehensive guidance for artiicial pancreas systems in November 2012. This guidance is helping researchers in academia and industry identify steps they need to take in the development of their artiicial pancreas systems before applying to the FDA for permission to test device safety and effectiveness in people or
to market their systems. Also, the April 2013 artiicial pancreas workshop was the fourth such collaborative workshop organized by the NIDDK, the FDA, and JDRF in less than a decade to stimulate discussion of the current state of the art in artiicial pancreas technology, technical dificulties and possible solutions, safety issues, and next steps.
While the NIH has supported research in this field for over two decades, in the last several years the NIDDK has intensified its artiicial pancreas research program as well as its collaborations with other NIH Institutes and JDRF. For example, since 2008, the NIDDK, in partnership with the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), has released four funding opportunity announcements to solicit innovative research on artiicial pancreas systems by small businesses. The NIDDK has also participated in the NICHD-led Diabetes Research in Children Network, or DirecNet, which has investigated the use of technological advances in the management of type 1 diabetes in children and adolescents. As a result of its own efforts and these collaborations, the NIDDK is currently supporting a multi-faceted program of research at academic centers and small businesses to:
- Conduct clinical studies of portable artificial pancreas devices;
- Make stable, fast-acting formulations of insulin and another hormone important to managing blood glucose levels, glucagon;
- Improve glucose sensors’ sensitivity and durability;
- Build and test devices that combine sensing and hormone delivery;
- Study physiological and behavioral factors to make artiicial pancreas use easier; and
- Develop the next generation of glucose-sensitive technology.
Through recent initiatives, the NIDDK is also fostering research training of bioengineers and development of an interdisciplinary workforce to develop innovative technologies for diabetes treatment, including artiicial pancreas systems. Notably, a signiicant portion of NIH-supported artiicial pancreas research over the past 15 years has been made possible by funds from the Special Statutory Funding Program for Type 1 Diabetes Research.
JDRF supports its own program of research on the artiicial pancreas, the Artiicial Pancreas Project, which it launched in 2006. Over the years, the NIDDK has increased collaboration with JDRF and other important funding entities, such as The Leona M. and Harry B. Helmsley Charitable Trust, to coordinate efforts so that there can be more eficient investment of resources to expedite advances in this ield. For example, the NIDDK and JDRF are both funding sites in the Artiicial Pancreas Consortium, a multi-site, international consortium of clinicians, engineers, and mathematicians who have tested early, hospital-based
versions of an artiicial pancreas and have started to test outpatient, wearable systems. Moreover, the NIDDK and JDRF have organized scientiic panels of artiicial pancreas investigators at the American Diabetes Association’s annual Scientiic Sessions, with the next one planned for June 2014.
The collaborative workshops organized by the NIDDK, the FDA, and JDRF, as well as the NIDDK and JDRF initiatives, have also inspired investment in artiicial pancreas technologies by other, private foundations. For example, The Leona M. and Harry B. Helmsley Charitable Trust has recently launched initiatives on the artiicial pancreas, such as the Trust’s Automated Insulin Delivery Initiative. The Trust also funds the “bionic pancreas” project (as described later).
As a result of research investments and collaborative activities to promote artiicial pancreas technologies, there has been rapid progress in the past few years toward achieving effective, wearable systems. For example, in just the last year:
- “Low glucose suspend” devices: The objective of these devices is to temporarily shut off insulin delivery when circulating glucose levels fall below a set threshold, to help prevent episodes of dangerously low blood glucose levels—an important aspect of artiicial pancreas functionality. A recently published clinical study supported by industry (Medtronic) demonstrated that hypoglycemia events were less frequent, and events at night were less severe and shorter in duration, in patients using a glucose-sensor augmented low glucose suspend device at home. In September 2013, the FDA approved the Medtronic Minimed 530G, the device that was used in this trial, for use by people with diabetes 16 years of age and older. This is the irst example of an artiicial pancreas technology approved under the FDA guidance released in November 2012.
- “Diabetes Assistant (DiAs)”: A number of investigators are developing and testing systems that close the loop between glucose sensing and insulin delivery using smartphone based technology, which would make the system practical for use outside of a hospital setting. A recently published study of one such system, the DiAs, which uses an Android-based smartphone, has demonstrated the feasibility of its use to control blood glucose levels in a hotel-based outpatient setting.
- Bihormonal bionic pancreas: To more fully recapitulate the hormonal controls of blood glucose levels lost in type 1 diabetes, some researchers are already working on systems that include both insulin, which lowers blood glucose levels, and glucagon, which raises them. Researchers working on a bihormonal bionic artiicial pancreas based on an iPhone platform recently completed two outpatient studies in adults and children, with encouraging results. The “bionic pancreas” effort has received support from the NIDDK, JDRF, and The Leona M. and Harry B. Helmsley Charitable Trust, among others.
In concert with academia and industry, the NIDDK/NIH, the FDA, and JDRF have collectively catalyzed very intense and productive activity in the ield of artiicial pancreas research. This joint commitment by public and private institutions to an active role in the development of an artiicial pancreas has fostered remarkable progress in recent years. Looking ahead, it is anticipated that these collaborative efforts will continue to lead to new successes in harnessing this new technology to
improve the lives of people with diabetes.