'Bionic Pancreas' Works for 5 Days in Outpatient Settings

Miriam E. Tucker

June 16, 2014

SAN FRANCISCO — Progress toward the development of a closed-loop "artificial pancreas" has hit a new milestone, improving blood glucose levels in adults and teenagers with type 1 diabetes for 5 days straight in real-world settings.

The findings, from 2 separate studies of 20 adults and 32 adolescents, respectively, were presented here at the American Diabetes Association (ADA) 2014 Scientific Sessions by Steven J. Russell, MD, PhD, of the diabetes unit at Massachusetts General Hospital and Harvard Medical School, Boston. The study results were also simultaneously published in the New England Journal of Medicine.

The so-called "bionic pancreas," being developed collaboratively between the Harvard group and a team led by Ed Damiano, PhD, from the department of biomedical engineering at Boston University, Massachusetts, is wearable and automated and incorporates glucagon in addition to insulin. (Some other investigational closed-loop systems use only insulin.)

"It's a big step forward, because it's the first time we've taken the bihormonal bionic pancreas and brought it into a realistic situation where we don't make any restrictions on [subjects'] diet, activities, or their routine. It's much more challenging than a hospital environment where we've tested the system before," Dr. Russell told Medscape Medical News.

Stuart A. Weinzimer, MD, associate professor of pediatrics at Yale University, New Haven Connecticut, who has done extensive research in this area, added, "We've been anxiously awaiting the results of this study. I think it's very exciting. It was an incredibly ambitious project."

But Dr. Weinzimer noted that the system remains imperfect, as patients still experienced some highs and lows requiring intervention. "I think we're never going to get rid of the human interaction with the system, at least until we have much faster insulins. There's always a trade-off between control and involvement, and the artificial pancreas isn't going to remove that completely."

The "bionic-pancreas" device comprises an iPhone, which runs the control algorithm, and a Dexcom continuous glucose monitor (CGM) connected by a custom hardware interface that displays the CGM readings and insulin and glucagon doses. Both the insulin and the glucagon are delivered subcutaneously by t:slim infusion pumps (Tandem Diabetes Care).

The system allows for announcement of meals prior to eating to trigger a partial meal-priming insulin bolus.

Patients received 5 days of bionic-pancreas treatment and 5 days of usual pump therapy in random order.

Adult Study: Differences Were More Pronounced at Night

Dr. Steven J. Russell

In the adult study, the 20 participants (aged 21 and older) lived at home during the usual-care period and carried out their normal activities while wearing their own insulin pump and their own CGM if desired. During the bionic-pancreas period, they stayed in a hotel and were allowed to move freely within a 3-mile area in Boston, accompanied by a staff member.

The primary outcome of the study was mean plasma glucose level during the 5-day bionic-pancreas period, which was 138 mg/dL (range, 116-166 mg/dL), and the time spent with plasma glucose levels below 70 mg/dL was 4.8% and below 60 mg/dL was 2.3%. Mean glucose levels on CGM were similar to the plasma glucose readings.

But to allow time for adaptation of the bionic-pancreas system, results weren't compared with the control period until day 2. On days 2 through 5, mean glucose level on CGM was 133 mg/dL with the bionic pancreas, compared with 159 mg/dL with usual care (P < .001). The percentage of time with glucose levels below 70 mg/dL was 4.1% vs 7.3% (P < .001) and below 60 mg/dL was 1.5% vs 3.7% (P = .02).

Differences between bionic-pancreas and control periods were more pronounced at night, with mean CGM values of 126 vs 169 mg/dL (P < .002), the percentage of time below 70 mg/dL 1.8% vs 6.2% (P = .01) and below 60 mg/dL 0.4% vs 3.3% (P = .01).

There were no severe hypoglycemic events. Nausea with and without vomiting each occurred once within 2 hours after a glucagon dose. Three insulin-infusion sets and 1 glucagon-infusion set during the bionic-pancreas period were removed due to pain or inflammation.

Adolescents Participate in Summer Camp Study

The adolescent study took place at a diabetes summer camp, where participants stayed in cabins and were closely monitored.

Among the adolescents, who were aged 12 to 21, the mean plasma glucose level was also lower during the bionic-pancreas period than during the control period — 138 mg/dL vs 157 mg/dL (P = .004) — but the percentage of time spent in the hypoglycemic range was similar during the 2 periods (6.1% vs 7.6%, P = .23).

Over the 5 days, interventions for hypoglycemia were necessary in 1 of every 1.6 days during the bionic-pancreas period compared with 1 per 0.8 days during control time.

There were no episodes of severe hypoglycemia during the bionic-pancreas period, whereas there was 1 during the control period, with a plasma glucose level of 19 mg/dL that was successfully treated with oral carbohydrates. Three patients during each study period had transient hyperketonemia that resolved with a set change or after a technical problem was resolved in 1 case.

One patient reported nausea and 2 reported vomiting on 1 occasion each during the bionic-pancreas period, after glucagon had been given 2 to 5 hours earlier.

Next Steps: 2 More Studies, One in Younger Kids

Dr. Russell told Medscape Medical News that the group's next bionic-pancreas study is starting this week. It will enroll 12 patients age 18 and older at each of 4 US sites in a true "real-world" situation. Patients will have to live within a 30-minute radius and stay within a 60-mile radius so that investigators can intervene if necessary, but "other than that, we give them the bionic pancreas and send them home and see them again 11 days later."

And this summer they'll do another camp study similar to this one involving 6- through 11-year-olds, he said.

Dr. Weinzimer told Medscape Medical News that he worries a little about the complexity of the bihormonal system and what might happen if the glucagon pump fails but the insulin infusion continues. And, he said, he'd prefer a method in which "announcing" a meal isn't necessary.

Nonetheless, he said, "It's a major leap forward to outpatient closed-loop control. It's not going to be perfect, but it's still wonderful."

The study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the Leona M. and Harry B. Helmsley Charitable Trust, and the Earle Charlton Fund for Innovative Research in Diabetes and gifts from the Frederick Banting Foundation, Ralph Faber, and John Whitlock. Dr. Russell receives consulting fees from Medtronic and lecture fees from Tandem Diabetes, Sanofi, Eli Lilly, Abbott Diabetes Care, and Biodel. Equipment was loaned and technical assistance was provided by International Biomedical, Abbott Diabetes Care, Medtronic, Insulet, and Hospira. Dr. Weinzimer is on advisory panels or speaker's bureaus and/or consults for Medtronic, Animas, Tandem, Becton Dickinson, and Eli Lilly. He is a stockholder in Insuline.

N Engl J Med. Published online June 15, 2014. Article

American Diabetes Association 2014 Scientific Sessions; June 15, 2014. Abstract 237-OR

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