The U.S. Food and Drug Administration (FDA) cleared the iLet® Insulin-Only Bionic Pancreas System, which is designed to autonomously determine and deliver insulin doses to control blood-sugar levels, for people 6 years of age and older with type 1 diabetes (T1D). It includes an algorithm and an integrated infusion pump, which communicates directly with a compatible FDA-cleared integrated continuous glucose monitor (iCGM), enabling it to be an artificial pancreas, or automated insulin dosing (AID), system.

What’s new about this system? Ease-of-use. The iLet system is designed to have users enter only their weight for the iLet to initialize therapy. Immediately thereafter, the iLet begins controlling blood-sugar levels automatically, without requiring the user to count carbohydrates, set insulin delivery rates, or deliver additional insulin for meals or corrections. (Users do have to say whether the amount of carbs in a meal is small, medium, or large, but the algorithm learns over time in response to their individual insulin needs.)

The submission was based on a multi-center randomized insulin-only iLet Bionic Pancreas pivotal trial, which tested the insulin-only configuration in 440 adults and children 6 years and older with T1D. The trial met all key endpoints, demonstrating improved outcomes over standard of care for people living with T1D:

• Average HbA1c fell from 7.9% to 7.3% at 13 weeks
• An average of 2.6 hours more time-in-range (70-180 mg/dL) per day, improving from 51% to 65% at 13 weeks
• No increased risk of hypoglycemia

There are now multiple artificial pancreas systems on the market: The Medtronic 670G (2016), Tandem Control-IQ™ (2019), Medtronic 770G (2020), Insulet Omnipod 5 (2022), Medtronic 780G (2023), and, now, the iLet® Insulin-Only Bionic Pancreas System. (Tidepool Loop, an app that contains an algorithm that automates insulin dosing, has also been approved, but it has not yet announced its insulin pump manufacturer.)

Breakthrough T1D Impact

Breakthrough T1D started the Artificial Pancreas Project over 15 years ago to ensure people with T1D have better, more innovative ways to manage their type 1 diabetes until there are cures. Our goal was to ensure life-changing options for people with T1D and a competitive ecosystem that drove continuous innovation. To date, Breakthrough T1D has funded more than $140 million in artificial pancreas research.

Through these grants, Breakthrough T1D supported the development of the algorithm and preclinical and early clinical research—in partnership with the Helmsley Charitable Trust—through grants to:

• Firas El-Khatib, Ph.D., who received a Breakthrough T1D postdoctoral fellowship from 2006-2007 and is now co-founder and VP, Research & Innovation, at Beta Bionics
• Ed Damiano, Ph.D., co-founder and executive chair of Beta Bionics, from 2009-2011
• Steven J. Russell, M.D., Ph.D., who received a grant from 2013-2016 and is the principal investigator on all of the iLet clinical trials

This is a win for the T1D community and provides people with T1D another option to improve daily blood-sugar management, until cures are found.

Clinical trials are essential for delivering new devices and treatments to people with type 1 diabetes (T1D). There are currently over 100 actively recruiting studies for T1D in the U.S.

Participating in a clinical trial allows you to make an important contribution to the advancement of medicine. Below, meet two people who are helping improve the lives of people with type 1 diabetes and getting us closer to cures, one study at a time.

Meet Phyllis Kaplan

Phyllis Kaplan has been part of Breakthrough T1D for so long, it was before the “R.” “Back then it was just JDF,” she recalled.

Phyllis has lived with type 1 diabetes for more than 40 years. After several decades of volunteering in outreach and One Walks, she joined Breakthrough T1D professionally as a Community Engagement Manager for the Greater New England chapter in 2022.

She also supports the T1D community by participating in clinical trials—she’s currently in her eighth one! Phyllis has taken part in studies on the impact of T1D on the liver, insulin pump infusion sets, and using glucagon in a bionic pancreas, to name a few.

“I consider clinical trial participation as my ultimate form of diabetes advocacy,” she said. “Without clinical trial participants there can’t be clinical trials.  Without clinical trials, there can’t be new treatment options.”

Phyllis partners with her chapter’s Clinical Trial Education Volunteer (CTEV), Amanda Gilchrist, to build a culture of research participation in the T1D community. “Being in a clinical trial is like being at the forefront of research,” she said. “It isn’t always easy, but it’s always important.”

Meet Amanda Gilchrist

When second-grade teacher Amanda Gilchrist received a T1D diagnosis, she was still adjusting to her daughter Emmie’s T1D diagnosis just a year earlier. She spent months learning about T1D so she could be a better caretaker for Emmie, but her diagnosis still came as a complete surprise.

Clinical trials sparked Amanda’s interest after she heard that researchers often struggle to find participants. “It shocked me to learn some trials don’t complete due to a lack of people signing up,” she said. “We need clinical trials to move forward with research, new devices, or a cure.”

She immediately got Emmie involved in clinical trials, including testing a new continuous glucose monitor (CGM) and artificial pancreas (AP) system. “Being in type 1 diabetes clinical trials makes Emmie feel like she’s a scientist working to help others with T1D,” she said.

Amanda has taken part in clinical trials, too. One aimed to reduce parental concerns about low blood sugar. Another explored the potential of plasmid therapy to retrain the immune system. She’s currently in a clinical trial for an automated insulin delivery system where it isn’t necessary to count carbs.

Amanda is also a Clinical Trial Education Volunteer (CTEV). She works with Phyllis to provide members of her local T1D community with information on clinical trials in their area. She loves helping families find a clinical trial that works for them. “You can be a hero like my daughter and move T1D science forward!”

Learn more about clinical trials and find local opportunities in your area.

These resources are made possible in part through the support of
Dompe and Vertex Pharmaceuticals.

Cell replacement therapies aim to provide insulin on demand from cells implanted in the body, but, today, the shortage of donor beta cells and the need for chronic immunosuppression limit its widespread clinical adoption.

Breakthrough T1D is funding researchers around the world working on every aspect of cell replacement technologies to make them a reality—a cure—for type 1 diabetes (T1D). There’s a lot to figure out an many obstacles to overcome until these therapies realize their potential. These include:

• Cell Supply: How do we make enough cells for everyone who needs them? Do we use a renewable beta cell source from stem cells or animal models?
• Immunoprotection: How do we protect the cells from the hostile environment in the body once they are transplanted—and where is the best place for them to be transplanted?
• Oxygen and Other Nutrients: How do the transplanted cells get the resources they need to survive while keeping the immune system out?

Several approaches, however, are aiming to make these obstacles a thing of the past. Read more below.

Blood vessel growth + Local immunosuppression = A win for islet cell therapy

A way to combine islets—the group of pancreatic cells that produce insulin and glucagon—with blood vessels before transplantation would give them a virtually infinite supply of oxygen and nutrients, but it exposes the islets to the immune system, requiring systemic immunosuppression to prevent rejection. A novel encapsulation approach that integrates blood vessel growth for islets with effective immune evasion to prevent rejection could work.

Encapsulation: An advanced form of transplantation where a material is designed to keep cells protected from immune attack, while letting insulin out and letting oxygen and other nutrients in.

Enter the NICHE. It stands for Neovascularized Implantable Cell Homing and Encapsulation device. It is a quarter-sized device with two reservoirs—one for islets which have undergone the process of developing blood vessels and one for local immunosuppressant delivery—for the transplantation of islets to treat T1D. It is the first platform that integrates both blood vessel growth plus local immunosuppression into a single, implantable device.

In animal models, this device restored healthy glucose levels and eliminated T1D symptoms for more than 150 days while avoiding the adverse effects of anti-rejection therapy by administering immunosuppressive drugs only where the transplanted islet cells were located.

The results pave a path for the continued translational development of the NICHE technology, which has the potential to transform the field of islet transplantation.

Engineering a pancreas-like organ for transplantation

An unlimited source of less immunogenic islets? Check. Blood vessel growth prior to transplantation? Check. A novel scaffold to put these into? Check.

What does this mean?

You have an immune-protected, functional pancreatic organ—the first bioengineered device aimed to treat T1D.

What’s more? Results showed immediate function upon transplantation, preserving normal blood-sugar levels for up to 18 weeks.

Eventually, with further testing, this could be the next phase of cell replacement therapy, overcoming the current limitations in islet transplantation to generate a bioengineered device for the treatment of T1D.

Transplantation without the need for any immunosuppression

Vertex Pharmaceuticals—which acquired Semma Therapeutics in 2019 and ViaCyte in 2022, both of which had Breakthrough T1D or Breakthrough T1D T1D Fund support, with the goal of developing stem cell-derived replacement therapies for T1D—has a new first: No immunosuppression.

VX-264 takes the stem cell-derived therapy VX-880—which is being used to try to restore the body’s ability to produce insulin combined with immunosuppression—and encapsulates it with an immunoprotected device. The trial will begin to recruit later this year.

In Vertex’s phase I/II clinical trial, the first person to receive VX-880 is 100% insulin independent 270 days after receiving the therapy.

“Advancing research in cell replacement is a core pillar of Breakthrough T1D’s research strategy and we have been a significant supporter of these and other promising approaches,” said Jaime Giraldo, Ph.D., Associate Director of Research at Breakthrough T1D. “There is a revolution in cell therapy technologies and approaches, which will bring us one day to finding cures for type 1 diabetes.”

To one day cure type 1 diabetes (T1D), we must halt the destruction of beta cells that produce insulin. A new Breakthrough T1D-funded study suggests a potential path to keeping beta cells healthier for longer—meaning their body will still make insulin for more time, known as the “honeymoon” phase—for newly diagnosed youth.

The clinical trial looked at whether the effects of a hybrid closed loop system (also known as an artificial pancreas system or automated insulin delivery system) and/or verapamil preserved beta cell function one year after diagnosis in children and teens with T1D.

The study found that newly diagnosed individuals on verapamil were making more insulin one year after diagnosis than those on placebo, with the average C-peptide, which is used to measure insulin, being 30% higher for the verapamil group compared to placebo. HbA1c was 6.6% in the verapamil group versus 6.9% in the placebo group, at one year. (There was no change, however, in the hybrid closed loop system arm.)

“Safe, effective therapies are urgently needed to delay disease progression in people recently diagnosed with type 1 diabetes, an area of high priority for Breakthrough T1D,” said Sanjoy Dutta, Ph.D., Breakthrough T1D chief scientific officer. “The CLVer study is the second trial showing that verapamil, an inexpensive and widely used blood pressure medication, can preserve beta cells in the new onset period, making us one step closer to our goal of having disease-modifying therapies widely available for people with type 1 diabetes.”

But you don’t have to rely on what the blog said; from the clinical study authors: “oral verapamil was well-tolerated and slowed the rate of beta cell decline in youth with newly-diagnosed type 1 diabetes….In view of the favorable safety profile…once-a-day oral administration, and low cost, initiation of verapamil therapy should be considered for newly-diagnosed type 1 diabetes.”

What Does It Mean for the T1D Community?

Today, verapamil is not an approved therapy for newly diagnosed people with T1D, and it will not be in the very near future. There are additional studies that may need to be conducted to validate the results and learn so that all the benefits of the drug are known, as well as all of the potential side effects. Breakthrough T1D has a strategic road map to answer all these questions. These include:

• What are the long-term effects of the drug?
• Does the preserved beta cell function last?
• Can this drug help people in stage 2 T1D?

There’s a lot more we must learn!

What Comes Next?

Breakthrough T1D will gather longer-term evidence of verapamil’s effectiveness, while in the near term sharing these data with the clinical community and other health care leaders to facilitate future access:

• Breakthrough T1D has a grant for a follow-up study for three years to see if C-peptide benefits persist
• Breakthrough T1D is funding several clinical trials to validate the results of this study and see if verapamil is effective when used in conjunction with other disease-modifying therapies, such as Tzield™ (teplizumab-mzwv)

This year’s Advanced Technologies & Treatments for Diabetes (ATTD) meeting, taking place from February 22-25, will have 45 presenters who are or were Breakthrough T1D-funded researchers working to treat, prevent and, ultimately, cure type 1 diabetes (T1D) and its complications. Sanjoy Dutta, Ph.D., Breakthrough T1D Chief Scientific Officer, Jon Rosen, Ph.D., Director of Research, and Anastasia Albanese-O’Neill, Ph.D., APRN, CDCES, Director of Community Screening and Clinical Trial Education, will be there, too, chairing sessions on monitoring and glucose control.

Here are select highlights of Breakthrough T1D-funded research that will be featured:

• In a Breakthrough T1D Session chaired by Jon Rosen, Ph.D., on February 23, presenters David O’Neal, M.D., University of Melbourne, Rodica Busui, M.D., Ph.D., University of Michigan, and Idan Tamir, Ph.D., QuLab Medical, will talk about the clinical need for continuous ketone monitoring, in addition to continuous glucose monitoring, to enable SGLT therapy—which can lower your HbA1c levels but has an increased risk of developing diabetic ketoacidosis (DKA)—use for heart and kidney health for people with T1D.
• On February 24, we will hear the latest Breakthrough T1D-funded clinical trial results from Gregory Forlenza, M.D., University of Colorado, who was one of the investigators on the phase III CLVer (Closed Loop + Verapamil, pronounced “clever”) study to test whether a hybrid closed loop (i.e., artificial pancreas) system and/or verapamil preserves beta cell function one year after diagnosis.

Diabetic ketoacidosis (DKA)—a life-threatening complication—is an abundance of ketones in the blood, which typically also happens when blood sugar is very high. With SGLT therapy, however, DKA presents with blood-sugar levels at normal or near it. Because of this, ketone sensors will be crucial to regulatory approval and access to SGLT drugs.

• In another Breakthrough T1D Session introduced by Sanjoy Dutta, Ph.D., you will hear from Michael Haller, M.D., University of Florida, Chantal Mathieu, M.D., Ph.D., KU Leuven, Belgium, and Kimber Simmons, M.D., University of Colorado, on which technology to use for monitoring pre-symptomatic T1D after autoantibodies are detected, on February 25.
• Also on February 25, the International Society for Pediatric and Adolescent Diabetes (ISPAD) will have a session on global T1D, with Jamie R. Wood, M.D., Case Western Reserve University and secretary general of ISPAD, presenting on T1D technology in low and middle low-income countries, using insights from the T1D Index, a first-of-its-kind tool that provides the most accurate and comprehensive global figures of T1D across the world.

Stay tuned on social media (Facebook at @breakthrought1dhq, Twitter at @BreakthroughT1D, and LinkedIn) for exciting news at ATTD!

For some adults who use inhaled insulin at mealtimes, it provides another option to manage their diabetes and it is taken with the first bite of food. But it’s only available for people who are 18+ years old. Children and most teens do not currently have this option. The results of a clinical trial recruiting participants may change that.

Younger kids may be unable to understand type 1 diabetes and effectively manage their blood sugar. For tweens and teens, managing diabetes can add an extra layer of stress, particularly when it comes to meals and snacks. Hormonal changes during these years make glucose levels unpredictable, and adolescents tend to eat more meals away from home and are “likely to engage in eating as a major social event with peers.”¹

Stopping for a snack after school, participating in a classroom party, eating a mid-morning snack; this could be managed by taking injected insulin about 15-20 minutes before eating or drinking. But children and teens don’t always plan ahead (their executive functioning skills are still developing). They can eat randomly, without time for preplanning insulin doses.

But what if it was safe and effective to take a rapid-acting inhaled insulin just as they start eating? The INHALE-1 clinical trial is finding out.

This study aims to evaluate the safety and effectiveness of a rapid-acting inhaled insulin product for use in children and teenagers with diabetes.

Who Can Join?

• Children and teenagers ages of 4-17
• Diagnosed with type 1 or type 2 diabetes and using mealtime insulin (vial or pen, no pumps)
• A1c is 7%-11%
• No recent history of asthma (in the last 12 months) or other lung conditions
• No smoking or vaping

What’s Involved?

• The study involves clinic visits, blood draws, and lung function tests
• Qualified participants will either take inhaled insulin for 12 months or continue mealtime injectable insulin for 6 months and then switch to inhaled insulin for the final 6 months
• Inhaled insulin will be provided at no cost
• Participants will be asked to check their glucose level frequently using a continuous glucose monitor (CGM), which will be provided throughout the study

Where Is It Recruiting?

Recruitment is taking place, as of now, at 22 sites located in California, Florida, Georgia, Idaho, Indiana, Iowa, Kentucky, Maryland, Massachusetts, Nevada, New Jersey, New York, Ohio, Pennsylvania, Tennessee, and Texas. Find the site location nearest you on the National Institutes of Health’s (NIH) ClinicalTrials.gov website.

If you and your child or teen are interested in becoming involved, contact 1-844-INHALE1.

Facebook Live Event

To learn more about the INHALE-1 clinical trial, you can also watch our Facebook Live event titled “Children are Not Little Adults: The Importance of Pediatric Research,” featuring:

• Anastasia Albanese-O’Neill, Ph.D., APRN, CDCES, Director, Community Screening and Clinical Trial Education, Breakthrough T1D
• Nicole and Sydney Thomas
• Michael J. Haller, M.D., Professor and Chief of Pediatric Endocrinology, University of Florida, and INHALE-1 Protocol Chair

This educational content is made possible with support from MannKind Corporation. Breakthrough T1D produces this content to provide information to our supporters about their potential options for managing their T1D and not as an endorsement of products. Editorial control rests solely with Breakthrough T1D.

¹Borus JS, Laffel L. Adherence challenges in the management of type 1 diabetes in adolescents: prevention and intervention. Curr Opin Pediatr. 2010 Aug; 22 (4): 405-11. doi: 10.1097/MOP.0b013e32833a46a7.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) is really cool! First of all, it’s an organization that aims to promote research, education, and advocacy in children, adolescents, and young adults with diabetes—across the globe. Second, they offer fellowships for research training, and two of them are co-funded by Breakthrough T1D!

Now, it’s time to announce the awardees for one of them, the ISPAD-Breakthrough T1D Research Fellowships, which provide $25,000 to people under the age of 40 who wish to pursue a career in diabetes related research.

Let’s meet them:

Vanessa Jewell, Ph.D., OTR/L, an associate professor at Creighton University in Omaha, Nebraska, will evaluate a newly developed T1D assessment, Diabetes Health Management and Distress Scale—Parents of Young Children. It is the first known assessment to measure two areas: 1) diabetes management routines of parents caring for young children with diabetes; and 2) parent-specific diabetes distress, from an occupational therapy perspective.

Emilia Kowalczyk, M.D., Ph.D. (expected), a clinical fellow at the Medical University of Warsaw, Poland, will test the hypothesis that “super bolus”—a combination of: 1) an increased dose of mealtime insulin, in order to quickly cover the high glycemic index carbs; and 2) a suspended non-mealtime insulin during the next 2-4 hours, in order to account for the increased levels of active insulin in circulation—is an effective strategy to prevent post-mealtime blood-sugar levels compared to the normal non-mealtime insulin.

Claudia Piona, M.D., Ph.D. (expected), is a pediatrician at the University Hospital of Verona and a Ph.D. student at the University of Verona. With the support of the ISPAD-Breakthrough T1D Research Fellowship, Dr. Piona will evaluate the associations between early signs of diabetic complications, using metrics measuring short-term glycemic control, glucose variability, and oxidative stress, in children and youth with T1D. The study will advance the role of these factors leading to the development of diabetes complications in the pediatric population.

Rachel Wasserman, Ph.D., a licensed clinical psychologist and assistant research scientist at Nemours Children’s Hospital, Orlando, Florida, aims to engage adolescents with T1D via a private, online forum to provide suggestions and feedback for a new, T1D-focused risk-taking prevention intervention, and will work with stakeholder representatives to apply findings from the online forum to produce a novel T1D-relevant adolescent risk-taking intervention.

Please visit the ISPAD site to learn more about this fellowship and how to apply (the deadline is August 28).

Want to hear more about ISPAD? We’ll be writing a longer piece about the truly incredibly (not hyperbole) impact these grants have in the next few weeks!

Stem cells—first isolated by scientists in 1998—have two unique characteristics, with unique translatable potential: (1) They can be made to replicate themselves again and again without changing their essential nature, and (2) they can develop into virtually any type of human tissue. Stem cells have the potential to lead to treatments for type 1 diabetes (T1D), but it has taken us more than 20 years to get to this point. Read on.

Hear more from Dr. Melton about his search for T1D cures in our Meet the Scientist Video.

[1] Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N. Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A. 2000; 97 (21): 11307-11312. https://doi.org/10.1073/pnas.97.21.11307

[2] D’Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol. 2006 Nov; 24 (11): 1392-401. https://doi.org/10.1038/nbt1259

[3] https://www.breakthrought1d.org/blog/2014/08/19/jdrf-partner-viacyte-to-immediately-initiate-type-1-diabetes-clinical-trial

[4] https://clinicaltrials.gov/ct2/show/results/NCT02239354

[5] Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, Asadi A, O’Dwyer S, Quiskamp N, Mojibian M, Albrecht T, Yang YH, Johnson JD, Kieffer TJ. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. 2014 Nov; 32 (11): 1121-33. https://doi.org/10.1038/nbt.3033

[6] Pagliuca FW, Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D, Melton DA. Generation of functional human pancreatic β cells in vitro. Cell. 2014 Oct 9; 159 (2): 428-39. https://doi.org/10.1016/j.cell.2014.09.040

[7] https://www.breakthrought1d.org/blog/2019/09/04/semma-therapeutics-backed-jdrf-t1d-fund-acquired-major-biopharma-company/

[8] https://www.breakthrought1d.org/blog/2019/10/03/viacyte-announces-insulin-production-people-t1d/

[9] Pagliuca FW, Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D, Melton DA. Generation of functional human pancreatic β cells in vitro. Cell. 2014 Oct 9; 159 (2): 428-39. https://doi.org/10.1016/j.cell.2014.09.040

[10] Hogrebe NJ, Augsornworawat P, Maxwell KG, Velazco-Cruz L, Millman JR. Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells. Nat Biotechnol. 2020; 38 (4): 460-470. https://doi.org/10.1038/s41587-020-0430-6

[11] Maxwell KG, Augsornworawat P, Velazco-Cruz L, Kim MH, Asada R, Hogrebe NJ, Morikawa S, Urano F, Millman JR. Gene-edited human stem cell-derived β cells from a patient with monogenic diabetes reverse preexisting diabetes in mice. Sci Transl Med. 2020 Apr 22; 12 (540): eaax9106. https://doi.org/10.1126/scitranslmed.aax9106

[12] https://www.breakthrought1d.org/blog/2021/02/01/vertex-new-horizon-curing-type-1-diabetes/

At the American Diabetes Association’s 82nd Scientific Sessions, which was held in person (as well as virtually) from June 3-7, scientists presented on some of the most important topics, from stem cell-derived cell replacement trials to type 1 diabetes (T1D) screening to artificial pancreas technologies, all with the same goal: Ending T1D.

Breakthrough T1D played the roles of presenter, educator, and active learner—and was the key funder and supporter of nearly all the top advances shared in T1D research. There were many fantastic results that came through the ADA’s Scientific Sessions. Here is Aaron J. Kowalski, Ph.D., CEO of Breakthrough T1D, with the key takeaways from the conference, and there is a written summary of Breakthrough T1D highlights below.

You can view all of the oral and poster presentations on the Diabetes journal website.

Cures

Stem Cell-Derived Beta Cell Therapy: Advancing Clinical Trials

Breakthrough T1D Research Area: Cell Therapies

Cell replacement therapies, including stem cell-derived islet therapy, were on fire, with Vertex Pharmaceuticals and ViaCyte leading the way in clinical trials. Vertex launched its clinical trial of VX-880, a stem cell-derived beta cell therapy in T1D, in combination with immunosuppressive therapy to protect the cells from rejection, in the summer of 2021. To date, three participants have received the drug, and one is now insulin independent! ViaCyte, in partnership with CRISPR Therapeutics, initiated its first-in-human gene-edited, stem cell replacement therapy, without immunosuppression, called VCTX210.

Breakthrough T1D Leadership

Vertex’s VX-880 therapy was pioneered by Doug Melton, Ph.D.—who moved from Harvard to Vertex Pharmaceuticals to work on their stem cell-derived cell replacement therapies—after successfully transforming stem cells into beta cells in 2014. Another pioneer in cell replacement therapies for T1D is Timothy Kieffer, Ph.D., who also recently moved from the University of British Columbia to serve as Chief Scientific Officer at ViaCyte. They had Breakthrough T1D funding from 2000 on.

We also heard from Sernova, who provided an update on the phase I/II clinical trial of their Cell Pouch™—an implantable device designed to form a natural environment and allow the survival and function of insulin-producing (islet) cells. The first three individuals to receive the therapy into the Cell Pouch™, with a supplemental marginal dose of islet cells via the portal vein, have been insulin independent for 2 years, 6 months, and 3 months, respectively. Breakthrough T1D continues to support Sernova to make their Cell Pouch part of the cure portfolio.

Meeting attendees also heard clinical and preclinical data updates from several investigations on encapsulation and immune-tolerance strategies to protect transplanted islet cells from the immune system, featuring a world-renowned set of T1D researchers, including Breakthrough T1D-funded James Shapiro, M.D., Ph.D. (who is known for his leadership on the Edmonton Protocol), and Andrew R. Pepper, Ph.D., of the University of Alberta, Canada, Bernhard Hering, M.D., from the University of Minnesota, and José Oberholzer, M.D., of the University of Virginia.

Immune Mechanisms of T1D: Innate Versus Adaptive Immunity…or Both

Breakthrough T1D Research Area: Disease-Modifying Therapies

Adaptive immune cells are responsible for T1D, but beta cell stress and dysfunction precede this onslaught, with innate immune cells taking charge. It turns out that the prohormone to islet amyloid polypeptide (proIAPP, for short)—as C. Bruce Verchere, Ph.D., and Rebecca Hull-Meichle, Ph.D., discussed in their presentations—is elevated prior to clinical diagnosis, in addition to proinsulin—the precursor to insulin. proIAPP, in turn, sparks inflammation and innate immune cell damage. Dr. Verchere has developed a test to measure two kinds of proIAPP in humans, which, ultimately, will provide new insight into the immune cell types and immune mechanisms leading to beta cell function and pave the way for new therapies and biomarkers of beta cell stress.

Breakthrough T1D Leadership

Dr. Verchere received a Breakthrough T1D postdoctoral fellowship beginning in 1992 and Dr. Hull-Meichle received one in 2001-2003. The titles, respectively: “Role of Islet Amyloid Polypeptide in Normal and Abnormal Islet Function” and “The Role of Islet Amyloid Formation in Diabetes.” More recently, Heather Denroche, Ph.D., who Dr. Verchere credits in his presentation, received a Breakthrough T1D postdoctoral fellowship from 2014-2017 and an advanced postdoctoral fellowship from 2018-2022.

“Breakthrough T1D’s support has been instrumental to my development as a scientist and allowed me to make valuable contributions to type 1 diabetes research….I am truly grateful for this experience.”

– Heather Denroche, Ph.D.
Director, Preclinical Development
Integrated Nanotherapeutics

Dr. Verchere is now leading the Breakthrough T1D Center of Excellence at the University of British Columbia, where he is working on immune and beta cell therapies, including stem cell-derived therapies, with Dr. Kieffer; James Johnson, Ph.D., who received a Breakthrough T1D Career Development Award in 2005-2010; Francis Lynn, Ph.D., who was a Breakthrough T1D postdoc from 2004-2006, advanced postdoc from 2007-2009, and a Breakthrough T1D Alan Permutt Career Investigator from 2012-2016; and Megan Levings, Ph.D., who has received two Breakthrough T1D grants since 2015 and has been a mentor to two Breakthrough T1D postdocs.

General Population Screening: It’s Time

Breakthrough T1D Research Area: Screening

Several Breakthrough T1D-funded researchers presented on the current state of screening for genetic risk and/or T1D-related autoantibodies—antibodies that are directed toward your own body. Chantal Mathieu, M.D., Ph.D., gave a spirited talk about why it’s time to screen for T1D in the general population. The first point: T1D is a serious and important health problem and we have learned a lot from family screening and prevention studies. The second point: Decreasing diabetic ketoacidosis (DKA)—a complication of T1D due to a shortage of insulin levels in the body—should be, in itself, enough to warrant population screening. Post-screening, we must be ready with follow-up and guidance so families know what to do with autoantibody status, including clinical trials, like teplizumab—and screening will help identify populations who can benefit from them.

“100 years after the development of insulin, we still have people dying from DKA in all of our countries.”

– Chantal Mathieu, M.D., Ph.D.
KU Leuven, Belgium
Coordinator, INNODIA

Breakthrough T1D Leadership

As a result of decades of Breakthrough T1D-funded research, we can identify those at highest risk for developing T1D—two or more autoantibodies—and we have funded screening programs since they were first introduced in the late 1980s. More recently, Breakthrough T1D has a new initiative, T1Detect, to broaden screening to the general population. The goal: Global universal screening, which is key to developing disease-modifying therapies to keep the disease from progressing and, ultimately, prevent it entirely.

Improving Lives

From the DIY System and Klue to the Omnipod 5 and the iLet Bionic Pancreas

Breakthrough T1D Research Area: Artificial Pancreas

A ton of presentations focused on the artificial pancreas, or automated insulin delivery (AID), systems. The first: Results from the first randomized clinical trial testing a do-it-yourself, or DIY, open-source, community-built AID technology, using the OpenAPS algorithm plus the DANA or YpsoPump insulin pump and the Dexcom G6 continuous glucose monitor (CGM). The study included 100 children and adults in New Zealand who used the DIY system compared to those without the algorithm, headed by Breakthrough T1D grantees Martin de Bock, Ph.D. (who also gave the presentation), and Dana Lewis, the founder of the DIY artificial pancreas system movement. There was no severe hypoglycemia and no DKA and more participants achieved time-in-range of ˃70% using the OpenAPS algorithm, especially at night: Conclusion: The open-source AID was safe and effective in T1D compared to those without the algorithm.

Next up: Researchers presented results from a novel closed loop system that eliminates manual mealtime bolusing. Medtronic teamed up with Klue, an Apple-watch based application that detects eating hand gestures, to see if it could provide a “handsfree” artificial pancreas system. The system converted hand gestures to carb amounts and automatically bolused via a Medtronic 780G pump, and there was no significant difference in time-in-range achieved with this system compared to when participants bolused manually. By eliminating the burden of carb-counting, this system may improve the quality of life in persons with T1D without sacrificing glycemic outcomes.

Next: Omnipod 5, a tubeless hybrid closed loop system, in preschool children. Presenting on this was Daniel DeSalvo, M.D., who had a Breakthrough T1D postdoctoral fellowship from 2014-2016, with world-renowned researcher Bruce Buckingham, M.D. This was an extension study, to evaluate if glycemic outcomes continued at 12 months (compared to the 3 months in the pivotal trial), and they did! At 12 months, these children had lower A1c and greater time-in-range, and there was no DKA or severe hypoglycemia, indicating the potential long-term benefit of the Omnipod 5 in very young children with T1D. The Omnipod 5 is under FDA review for ages 2-5 years; let’s hope this study will resolve any fears that the AID system is not warranted in preschool aged children.

And finally, the results from the randomized insulin-only iLet bionic pancreas pivotal trial. These were presented by Steven Russell, M.D., Ph.D., at the Advanced Technologies & Treatments for Diabetes (ATTD) conference in April 2022, but now we have patient reported outcomes, presented by Jill Weissberg-Benchell, Ph.D., a professor at the Ann & Robert H. Lurie Children’s Hospital of Chicago, who discussed adults, with many reporting decreased distress, with less worry, guilt, and burnout due to increased time-in-range and no need to carbohydrate count, and youth, who reported positive experiences, including improved A1c, increased independence, and less time managing diabetes.

Breakthrough T1D Leadership

Dr. Russell received a Breakthrough T1D grant from 2013-2016 to refine the iLet pancreas, based upon the work of Ed Damiano, Ph.D., CEO of Beta Bionics, who Breakthrough T1D funded from 2009-2011, for his early research testing the safety and efficacy of a novel closed-loop system (including Firas El-Khatib, Ph.D., a Breakthrough T1D postdoctoral fellow in his lab). The results of this work helped to inform the development of the iLet bionic pancreas.

Diabetic Retinal Disease—Changing Before Your Eyes

Breakthrough T1D Research Area: Complications

Sobha Sivaprasad, M.D., reported on The Restoring Vision Moonshot, a “really radical” approach to end diabetic eye disease. The Early Treatment Diabetic Retinopathy Study (ETDRS) Scale, which is used to assess progression of retinopathy, was developed in the 1950s and was limited to point-in-time visual perception, but Dr. Sivaprasad is part of 50 global experts, who will review the literature on diabetic eye disease “in the next year,” and come up with an evidence-based updated retinopathy staging scale, creating recommendations incorporating decades of progress in functional imaging, other biomarkers, and metrics of quality of life. When it’s completed, the improved staging scale will lead to the development of early preventive therapies that will reduce vison-threatening retinopathy progression, and ultimately improving the quality of life for people with T1D.

Breakthrough T1D Leadership

Breakthrough T1D has supported eye disease research since its beginning, and has driven discoveries that have reduced the risk of blindness by 95 percent, including laser therapy and anti-VEGF treatments. In 2018, Breakthrough T1D and the Mary Tyler Moore and S. Robert Levine, MD, Foundation launched the Restoring Vision Moonshot, an ambitious initiative to reverse diabetes-related blindness and vision-threatening eye disease, which afflicts millions of individuals worldwide, held in honor of Mary Tyler Moore’s contributions to diabetes awareness and research.

Improving Health Equity in T1D

Breakthrough T1D Research Area: Psychosocial

Many Breakthrough T1D-funded researchers presented on psychosocial issues, including the stigma associated with diabetes, suicide and self-harm, and social inequities—economically vulnerable, minorities, food insecurity—in diabetes care. Specifically, Shivani Agarwal, M.D., M.P.H., and Jeffrey Gonzalez, Ph.D., who have a new grant from Breakthrough T1D to evaluate telehealth in minority children and teens, and David V. Wagner, Ph.D., who had a Breakthrough T1D advanced postdoctoral fellowship from 2000-2003 and a number of Breakthrough T1D grants since, spoke to the many populations who experience poor outcomes in T1D and how they can be addressed. There is a lot of work to be done to improve outcomes for all people with T1D, both in the United States and around the world, but Breakthrough T1D is committed to helping reduce the significant daily burden of this disease and, ultimately, improve health outcomes for the entire T1D community.

You can view all of the oral and poster presentations on the Diabetes journal website.

The American Diabetes Association’s (ADA) 82nd Scientific Sessions is almost here! From June 3-7, scientists and healthcare professionals will gather—in person!—at one of the largest conferences of diabetes researchers in the world. Breakthrough T1D researchers and Breakthrough T1D-funded scientists will also be there virtually to hear first-hand and present new study results that will improve outcomes for people with type 1 diabetes (T1D). Read what’s happening below.

ADA’s 82nd Scientific Sessions

• The Scientific Sessions is one of the largest gatherings of diabetes researchers in the world, where scientists and healthcare professionals share and learn about new diabetes advances with top experts.
• Breakthrough T1D-supported research has been highlighted at this annual event since Breakthrough T1D started funding research, showcasing new breakthroughs and therapies for people with T1D.
• This year, researchers will present 120+ studies—with Breakthrough T1D-funding at present or in the past—encompassing breakthrough clinical trials and significant research studies that are paving the way to novel and emerging treatments for T1D.
• Breakthrough T1D-funded researchers will outline new advances like:

Curing T1D

• Cell Therapies
  • What are the latest advances in stem cell-derived replacement approaches?
• Disease-Modifying Therapies
  • What role does innate immunity have in type 1?
  • Generating new beta cells in the body: True or false?
• T1D Screening
  • General vs. targeted screening: Which one is best?

Improving Lives

• Glucose Control
  • What are the benefits of artificial pancreas systems in real time?
  • How close are we to “smart” insulin?
• Complications
  • Diabetic kidney disease breakthroughs: Are we ready?
  • A new Breakthrough T1D staging system for diabetic eye disease: Are we ready for prime time?
• Psychosocial
  • How do we prevent disparities in T1D intervention and treatment?

Throughout the Scientific Sessions, Breakthrough T1D will be sharing updates to keep people apprised of the day-to-day happenings:

• Blog posts before, during, and after the ADA meeting
• A Facebook Live event (@BreakthroughT1DHQ) for each day, taking place the following day from 12:00 p.m. CT, with Breakthrough T1D-funded scientists talking about the takeaways
• A “happy hour” with CEO Aaron J. Kowalski, Ph.D., from 7-8 p.m. ET on Tuesday, June 7, speaking about the takeaways from the ADA Scientific Sessions and a Q&A period to answer questions from you, via Facebook Live (@BreakthroughT1DHQ)
• Interviews with Breakthrough T1D-funded scientists, who will go over their research and what it means to the T1D community, to be pushed out on social media
• To stay updated, follow us on Facebook (@BreakthroughT1DHQ) and Twitter (@BreakthroughT1D)