Artificial pancreas: The way of the future for treating type 1 diabetes

(Press-News.org) Montréal, January 28, 2013 – IRCM researchers, led by endocrinologist Dr. Rémi Rabasa-Lhoret, were the first to conduct a trial comparing a dual-hormone artificial pancreas with conventional diabetes treatment using an insulin pump and showed improved glucose levels and lower risks of hypoglycemia. Their results, published today in the Canadian Medical Association Journal (CMAJ), can have a great impact on the treatment of type 1 diabetes by accelerating the development of the external artificial pancreas.

The artificial pancreas is an automated system that simulates the normal pancreas by continuously adapting insulin delivery based on changes in glucose levels. The dual-hormone artificial pancreas tested at the IRCM controls glucose levels by automatically delivering insulin and glucagon, if necessary, based on continuous glucose monitor (CGM) readings and guided by an advanced algorithm.

"We found that the artificial pancreas improved glucose control by 15% and significantly reduced the risk of hypoglycemia as compared with conventional insulin pump therapy," explains engineer Ahmad Haidar, first author of the study and doctoral student in Dr. Rabasa-Lhoret's research unit at the IRCM and at the Department of Electrical and Computer Engineering at McGill University. "The artificial pancreas also resulted in an 8-fold reduction of the overall risk of hypoglycemia, and a 20-fold reduction of the risk of nocturnal hypoglycemia."

People living with type 1 diabetes must carefully manage their blood glucose levels to ensure they remain within a target range. Blood glucose control is the key to preventing serious long-term complications related to high glucose levels (such as blindness or kidney failure) and reduces the risk of hypoglycemia (dangerously low blood glucose that can lead to confusion, disorientation and, if severe, loss of consciousness).

"Approximately two-thirds of patients don't achieve their target range with current treatments," says Dr. Rabasa-Lhoret, Director of the Obesity, Metabolism and Diabetes research clinic at the IRCM. "The artificial pancreas could help them reach these targets and reduce the risk of hypoglycemia, which is feared by most patients and remains the most common adverse effect of insulin therapy. In fact, nocturnal hypoglycemia is the main barrier to reaching glycemic targets."

"Infusion pumps and glucose sensors are already commercially-available, but patients must frequently check the sensor and adjust the pump's output," says Mr. Haidar. "To liberate them from this sizable challenge, we needed to find a way for the sensor to talk to the pump directly. So we developed an intelligent dosing algorithm, which is the brain of the system. It can constantly recalculate insulin dosing based on changing glucose levels, in a similar way to the GPS system in a car, which recalculates directions according to traffic or an itinerary change."

The researchers' algorithm, which could eventually be integrated as software into a smart phone, receives data from the CGM, calculates the required insulin (and glucagon, if needed) and wirelessly controls the pump to automatically administer the proper doses without intervention by the patient.

"The system we tested more closely mimics a normal pancreas by secreting both insulin and glucagon," adds Dr. Laurent Legault, peadiatric endocrinologist and outgoing Director of the Insulin Pump Centre at the Montreal Children's Hospital, and co-author of the study. "While insulin lowers blood glucose levels, glucagon has the opposite effect and raises glucose levels. Glucagon can protect against hypoglycemia if a patient with diabetes miscalculates the necessary insulin dose."

"Our work is exciting because the artificial pancreas has the potential to substantially improve the management of diabetes and reduce daily frustrations for patients," concludes Dr. Rabasa-Lhoret. "We are pursuing our clinical trials to test the system for longer periods and with different age groups. It will then probably be introduced gradually to clinical practice, using insulin alone, with early generations focusing on overnight glucose controls."

### About the study This study was conducted with 15 adult patients with type 1 diabetes, who had been using an insulin pump for at least three months. Patients were admitted twice to the IRCM's clinical research facility and received, in random order, both treatments: the dual-hormone artificial pancreas and the conventional insulin pump therapy. During each 15-hour visit, their blood glucose levels were monitored as they exercised on a stationary bike, received an evening meal and a bedtime snack, and slept at the facility overnight.

Dr. Rabasa-Lhoret's research is funded by Diabetes Québec, the Canadian Diabetes Association, and the IRCM's J.A. De Sève Chair in clinical research. IRCM collaborators who contributed to study published in CMAJ include Maryse Dallaire, Ammar Alkhateeb, Adèle Coriati, Virginie Messier and Maude Millette. For more information on the study, please refer to the article summary published online by CMAJ: http://www.cmaj.ca/content/early/2013/01/28/cmaj.121265.abstract.

About diabetes Type-1 diabetes is a chronic, incurable disease that occurs when the body doesn't produce enough or any insulin, leading to an excess of sugar in the blood. It occurs most often in children, adolescents or young adults. People with type-1 diabetes depend on insulin to live, either through daily injections or with a pump. Diabetes is a major cause of vision loss, kidney and cardiovascular diseases.

According to the Canadian Diabetes Association, an estimated 285 million people worldwide are affected by diabetes, approximately 10 per cent of which have type 1 diabetes. With a further 7 million people developing diabetes each year, this number is expected to hit 438 million by 2030, making it a global epidemic. Today, more than 9 million Canadians live with diabetes or prediabetes.

About Dr. Rémi Rabasa-Lhoret Dr. Rémi Rabasa-Lhoret completed his doctoral degree (MD) with a specialization in endocrinology, metabolism and nutrition at the Université Montpellier in France. He then obtained a PhD in food sciences, and completed a postdoctoral fellowship in physiology and molecular biology. At the IRCM, Dr. Rabasa-Lhoret is Director of the Metabolic Diseases research unit, Director of the Diabetes, Metabolism and Obesity clinic, and Director of the research platform on obesity, metabolism and diabetes. He is an associate professor in the Department of Nutrition at the Université de Montréal. He is also adjunct professor in the Department of Medicine (Division of Experimental Medicine) at McGill University. Dr. Rabasa-Lhoret is a Clinical Research Scholar from the Fonds de recherche du Québec – Santé and holds the J.A. DeSève Chair in clinical research. For more information, visit www.ircm.qc.ca/rabasa.

About the IRCM Founded in 1967, the IRCM is currently comprised of 37 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry. It also houses three specialized research clinics, eight core facilities and three research platforms with state-of-the-art equipment. The IRCM employs 425 people and is an independent institution affiliated with the Université de Montréal. The IRCM Clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University.