Bionic Pancreas Reduces Hypoglycemia with Automated Glucagon Delivery

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Jun 14, 2016, 12:30 ET

NEW ORLEANS, June 14, 2016 /PRNewswire-USNewswire/ -- Delivering small doses of glucagon through an automated continuous glucose monitoring system can substantially reduce hypoglycemia (low blood glucose levels) in patients with type 1 diabetes, especially at night, according to a study presented at the American Diabetes Association's 76th Scientific Sessions^® at the Ernest N. Morial Convention Center in New Orleans. Glucagon is a hormone produced by the pancreas that raises blood glucose and works together with insulin, which has the opposite effect, to tightly regulate blood glucose concentrations. Both glucagon and insulin production are impaired in people with type 1 diabetes.

The double-blind, randomized, placebo-controlled crossover study included 22 patients with type 1 diabetes who used an insulin pump or multiple daily injections of insulin and who had reduced hypoglycemia awareness. For the duration of the study, all participants wore an experimental device that used a continuous glucose monitor to read their blood glucose levels and a pump to deliver small doses of glucagon in response to those levels. Participants were randomized to receive glucagon or placebo on alternate days, and patients had no knowledge of which treatment they received each day.

Low blood glucose was defined as levels lower than 60 mg/dl. On glucagon vs. placebo days, total exposure time to low blood glucose was reduced by 75 percent (851±748 vs. 3,414±2,242 mg/dl·min, p<0.0001) and at night by 91 percent (117±204 vs. 1,309±1,476 mg/dl·min, p<0.0001). There were also half as many symptomatic low-blood episodes on glucagon days vs. placebo days (0.6±0.4 vs. 1.2±0.8 incidents per day; p<0.0001), however, there was no difference in mean glucose levels (153±28 vs. 152±27 mg/dl, p=0.60). Side effects, such as self-reported nausea, were similar during glucagon and placebo days.

"Our study found that using automatic glucagon delivery reduced hypoglycemia by 75 percent during the day and 91 percent at night," said lead investigator Courtney Balliro, RN, BS, CDE, Clinical Research Nurse at the MGH Diabetes Research Center, Boston, MA. "We expected the device to prevent low blood sugar, however, we were pleasantly surprised by its efficacy. This device has the potential to simplify the lives of people with any disorder that causes low blood glucose levels by providing automatic treatment. Automatic treatment of hypoglycemia is particularly important for people with diabetes due to their increased risk for significant complications."

Low blood glucose levels can be particularly problematic at night, when patients are less likely to detect the symptoms, so episodes of low blood glucose may be prolonged. In addition, because hypoglycemia can cause mental confusion, patients must be aware and act quickly enough to treat it. If left untreated, hypoglycemia can also lead to seizures and other complications.

The American Diabetes Association's 76th Scientific Sessions, to be held June 10-14, 2016, at the Ernest N. Morial Convention Center in New Orleans, is the world's largest scientific meeting focused on diabetes. The 2016 Scientific Sessions is expected to attract more than 16,000 attendees and offers researchers and health care professionals from around the world the opportunity to share ideas and learn about the significant advances in diabetes research, treatment and care. During the five-day meeting, attendees receive exclusive access to more than 2,500 original research presentations, participate in provocative and engaging exchanges with leading diabetes experts, and can earn Continuing Medical Education (CME) or Continuing Education (CE) credits for educational sessions. The program is grouped into eight theme areas: Acute and Chronic Complications; Behavioral Medicine, Clinical Nutrition, Education and Exercise; Clinical Diabetes/Therapeutics; Epidemiology/Genetics; Immunology/Transplantation; Insulin Action/Molecular Metabolism; Integrated Physiology/Obesity; and Islet Biology/Insulin Secretion. Margaret A. Powers, PhD, RD, CDE, President, Health Care & Education, will deliver her address on Saturday, June 11, and Desmond Schatz, MD, President, Medicine & Science, will present his address on Sunday, June 12. The top eight abstracts of this year's Scientific Sessions will be presented on Tuesday, June 14, in the Presidents Oral Session. In total, the 2016 Scientific Sessions includes 378 abstracts in 50 oral sessions, 2,021 poster presentations including 59 moderated poster discussions, and 335 published-only abstracts. The Association's 2016 Scientific Achievement Awards and Lectures are:

Barbara B. Kahn, MD, Banting Medal for Scientific Achievement, the Association's highest honor. Kahn will deliver the Banting Medal Lecture, "Adipose Tissue, Inter-organ Communication, and the Path to T2D," on Sunday, June 12.
Tamas L. Horvath, DVM, PhD, Outstanding Scientific Achievement Award (OSAA), will present his OSAA Lecture, "Hunger-promoting Hypothalamic Neurons Control System Metabolism and Drive Complex Behaviors and Longevity," on Monday, June 13.
Sheri R. Colberg-Ochs, PhD, FACSM, Outstanding Diabetes Educator, will present her Lecture, "From Froot Loops^® to Fitness—My Journey as an Educator and PWD," on Saturday, June 11.
Edward W. Gregg, PhD, Kelly West Award for Outstanding Achievement in Epidemiology, will deliver his Lecture, "The Changing Tides of the Diabetes Epidemic—Smooth Sailing or Troubled Waters Ahead?," on Sunday, June 12.

Additional scientific research will be presented during 110 Symposia and nine Professional Interest Group sessions. The 76th Scientific Sessions also includes presence from more than 130 corporate and organizational exhibitors in nearly 100,000 square feet of exhibit space. Join the Scientific Sessions conversation on Twitter, #2016ADA.

About the American Diabetes Association
The American Diabetes Association is leading the fight to Stop Diabetes^® and its deadly consequences and fighting for those affected by diabetes. The Association funds research to prevent, cure and manage diabetes; delivers services to hundreds of communities; provides objective and credible information; and gives voice to those denied their rights because of diabetes. Founded in 1940, the Association's mission is to prevent and cure diabetes, and to improve the lives of all people affected by diabetes. For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit diabetes.org. Information from both of these sources is available in English and Spanish. Find us on Facebook (American Diabetes Association), Twitter (@AmDiabetesAssn) and Instagram (@AmDiabetesAssn).

76th Scientific Sessions
News Briefing: Closed-Loop Systems, Friday, June 10, 1:00 p.m.-1:45 p.m.

Oral Presentation: ADA Presidents Oral Session
Poster Presentation: Great Hall B
Session Time: Tuesday, June 14, 2016, 10:15 a.m.–12:15 p.m.

378-OR Closed Loop Glucagon Administration for the Automated Prevention and Treatment of Hypoglycemia in Type 1 Diabetes

COURTNEY BALLIRO, LAYA EKHLASPOUR, FIRAS ELKHATIB, DEBBIE MONDESIR, MANASI SINHA, KENDRA MAGYAR, MALLORY HILLARD, RAJENDRANATH SELAGAMSETTY, LISA DAO, ARYAN ESMAEILI, STEVEN J. RUSSELL, Boston, MA, Riverside, CA

Tight glycemic regulation is difficult to achieve without hypoglycemia. The effectiveness of suspending insulin delivery based on data from a continuous glucose monitor (CGM) is limited by the continued absorption of already-delivered insulin. An alternative approach is automated delivery of micro-doses of glucagon. We conducted a double-blinded, randomized, placebo-controlled crossover study involving 22 adult subjects with type 1 diabetes who used an insulin pump or multiple daily injections and who have reduced hypoglycemia awareness. Participants administered their own insulin as usual while receiving either glucagon or placebo (randomized daily) from an automated bionic pancreas. The primary outcome was area over the curve and <60 mg/dl (AOC<60), a measure of total hypoglycemia exposure.
On glucagon vs. placebo days AOC<60 mg/dl was reduced by 75% (851±748 vs. 3,414±2,242 mg/dl·min, p<0.0001) and there was a 91% reduction in AOC<60 at night (117±204 vs. 1,309±1,476 mg/dl·min, p<0.0001). There were half as many symptomatic hypoglycemia episodes on glucagon vs. placebo days (0.6±0.4 versus 1.2±0.8 incidents per day; p<0.0001), but no difference in mean CGM glucose (153±28 vs. 152±27 mg/dl, p=0.60). Self-reported nausea was not significantly different on glucagon vs. placebo days (1.1±0.6 vs. 0.4±0.7 cm on a 10 cm visual analog scale, p=0.053) and subjects correctly guessed their daily assignment to glucagon or placebo in a daily survey on only 42% of days. AOC measurements exhibited a significant decreasing trend over time in both groups (p=0.030) but there was no carry over effect from day to day (p=0.37). There was no unexpected or severe adverse events on either glucagon or placebo days. Automated glucagon administration effectively reduced hypoglycemia in patients with type 1 diabetes, and was well tolerated.

Author Disclosure Block:
C. Balliro: None. L. Ekhlaspour: None. F. Elkhatib: None. D. Mondesir: None. M. Sinha: None. K. Magyar: None. M. Hillard: None. R. Selagamsetty: None. L. Dao: None. A. Esmaeili: None. S.J. Russell: Advisory Panel; Author; Tandem Diabetes Care, Inc., Campanion Medical. Consultant; Author; Sanofi U.S.. Other Relationship; Author; Sanofi U.S., Dexcom, Inc., Tandem Diabetes Care, Inc., Eli Lilly and Company, Abbott Diabetes Care Inc., Insulet Corporation, Medtronic MiniMed, Inc., International Biomedical.