Investigators from the United States and Europe came together Monday for a symposium jointly sponsored by the ADA and the European Association for the Study of Diabetes. The symposium, Leveraging Metabolism to Prevent, Treat, or Cure Type 1 Diabetes, provided an extensive look at existing data and ongoing studies in several research areas, including closed-loop systems and immune modulation. Registered meeting attendees can view the full presentation at ADA2020.org through early September.
Closed Loop in the U.S.
Paul Wadwa, MD, Associate Professor of Pediatrics at the University of Colorado, Anschutz Medical Campus, reviewed data on closed-loop systems approved by the U.S. Food and Drug Administration, as well as data on systems still being developed and tested in trials.
“Currently available hybrid closed-loop systems, and those in trial, offer promise in addressing the need for improved glycemic control and can reduce the long-term risk for complications for people living with type 1 diabetes,” Dr. Wadwa said. “In the not too distant future, patients may have several options to choose from to optimize treatment using closed-loop technology.”
Dr. Wadwa shared data on several closed-loop systems that consistently showed improvement in targets, including time-in-range. He also discussed some feature enhancements that are planned for closed-loop systems currently in trials.
With Beta Bionics’ iLet, for example, users can announce meals, but it’s not required. The system will still function even if users don’t input carbs. In addition, iLet can be initialized with only the patient’s body weight, and insulin delivery is adapted based on the range of insulin requirements for the user. iLet is currently in a clinical trial.
Closed Loop in Europe
Charlotte K. Boughton, MRCP, PhD, a clinical lecturer researching the artificial pancreas at the University of Cambridge, United Kingdom, discussed closed-loop systems available and under development in Europe.
“We’re very fortunate to have four approved systems in Europe,” she said. “We have a great variety of choice, which I think is really important for patients.”
Like the data on systems in the U.S., the literature out of Europe shows closed-loop systems improve glycemic control and increase time in the target range for both adult and pediatric patients.
Dr. Boughton shared studies from Europe that demonstrated these benefits in specific patient groups, including children as young as one year old, pregnant women, and inpatients receiving dialysis. In pregnant women with type 1 diabetes, time-in-target overnight increased from 59.5% to 74.7% without a change in hypoglycemic events.
Type 1 Prevention in GPPAD
Data from the allergy community shows early introduction of peanuts can reduce the risk of developing a peanut allergy. Can a similar approach in children at high risk for type 1 diabetes prevent insulin autoimmunity?
Olga Kordonouri, PhD, shared insights from the Global Platform for the Prevention of Autoimmune Diabetes (GPPAD), which has developed a randomized controlled trial with oral insulin to try to answer that question. Dr. Kordonouri, Head of Clinical Research at Children’s Hospital AUF DER BULT in Hannover, Germany, said GPPAD has developed an international infrastructure, which enables the screening for type 1 diabetes in newborns from the general population. Screening is used to identify infants with an elevated genetic risk of developing type 1 diabetes for participation in the Primary Oral Insulin Trial (POInT), and monitor them for early diagnosis of type 1 diabetes.
Dr. Kordonouri said the goal is to identify infants with genetic predisposition in order to sensitize patients to insulin to train their immune systems and induce tolerance. Participants in the trial will receive either oral insulin provided as bulk human crystals in capsules or a placebo that is identical in appearance.
So far, GPPAD has screened 176,222 infants and identified more than 1,000 with 25-fold higher genetic risk for type 1 diabetes. Dr. Kordonouri said participation by parents has been well tolerated and the dropout rate has been low.
The primary outcome of POInT will be the development of persistent, confirmed, multiple beta-cell autoantibodies. The trial is expected to conclude by January 2025.
Closed Loop? Immune Modulation? Or Both?
During the symposium’s final presentation, Jay S. Skyler, MD, MACP, addressed the question, What will be the solution for type 1 diabetes—closed loop, immune modulation or both?
Dr. Skyler, Professor of Medicine, Pediatrics, and Psychology at the University of Miami, reviewed data on closed-loop systems and immune modulation in the context of what he called the four ideal therapeutic goals in type 1 diabetes: prevention of immune destruction; preservation of beta-cell mass or function; replacement or regeneration of beta cells; and automated insulin delivery.
Dr. Skyler said he doesn’t believe the solution will be closed-loop systems or immune modulation—or even both. He said prevention efforts such as the POInT study described by Dr. Kordonouri, as well as efforts to replace or regenerate beta cells, will also play a role.
“When we stop to consider the ideal therapeutic goals, there are still obstacles to all of them,” he said. “So we need a combination of a breakthrough and innovation. Breakthroughs and innovation create hope. As I look into the future, I think we’re going to see all of these things mature. Patients are going to have wide choice, and type 1 diabetes is going to be vastly different than it has been in the past.”