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 @myJDRF, Twitter at @JDRF, 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 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 or visit INHALE-1.

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 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.
• JDRF-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.
• JDRF-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 (@myJDRF) 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 (@myJDRF)
• 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 (@myJDRF) and Twitter (@JDRF and @JDRFResearch), with the hashtags #JDRFxADA and #ADA2022

In honor of the 100th anniversary of the first administration of insulin, Breakthrough T1D launched “100 Years, 100 Breakthrough T1D Scientists,” to tell the story of scientists and their discoveries, which put together the vast knowledge that we have about diabetes today.

The next one, for Healthy Vision Month: Treatments for diabetic eye disease.

Several decades ago, blindness and severe vision loss occurred in 40 percent of people with diabetes, but we have made progress since that time. Early detection and timely, appropriate treatment can reduce the risk of blindness by over 95 percent. Nonetheless, tens of millions of people, worldwide, still suffer from limited vision and blindness due to diabetes and the side effects of current treatment methods, and there is a real need to redouble our efforts to develop advanced and effective new therapies to restore vision and “cure” blindness in those so affected and prevent visual loss in the first place in people at risk.

The retina is a thin layer of specialized nerve tissue on the back wall of the eye. It converts light into electric signals that are transmitted to the brain where the images we “see” are generated. The center of the retina, called the macula, is responsible for the sharp clear vision needed for reading and other daily tasks.  Abnormal leaking from blood vessels damaged by diabetes can lead to swelling of the macula and vision loss. Diabetes also causes direct damage to nerve cells of the eye, including cells in the periphery of the retina. These changes stimulate the development of abnormal blood vessels, which are fragile and can bleed and further destroy the nerve tissue around them, scarring the retina and putting people at high risk for low vision and blindness.

Starting in the 1970s and 1980s, Breakthrough T1D supported the pioneering work of Lloyd M. Aiello, M.D., who, along with William P. Beetham, M.D., was a pioneer in introducing retinal photocoagulation therapy—a laser treatment that intentionally scars the peripheral retina in an effort to preserve the central vision needed for reading. Laser therapy has been successful in reducing the rate of blindness and severe central visual loss in proliferative retinopathy, as well as reducing progression of diabetic macular edema.

In the 1990s, Breakthrough T1D supported multiple research grants, including one proposed by Lloyd Paul Aiello, M.D., Ph.D. (Lloyd M.’s son), and George King, M.D., that showed that levels of VEGF, a protein the body makes which promotes the growth of new blood vessels in the eye, were elevated in people with diabetic retinopathy. Blocking VEGF substantially reduced the development of these fragile, leaky new blood vessels, suggesting that inhibiting VEGF might be a potential treatment for diabetic retinal disease.

For their contributions to research, Dr. Lloyd M. Aiello, Lloyd P. Aiello, and George King received prestigious Breakthrough T1D awards; the former two were given the prestigious David Rumbough Awards, and the latter was given the Breakthrough T1D Mary Tyler Moore and S. Robert Levine, MD Award for Excellence in Clinical Research.

Clinical Development and Regulatory Approval

Lucentis® (ranibizumab) and Eylea® (aflibercept), which are designed to inhibit VEGF, are two approved therapies for diabetic macular edema and diabetic retinopathy. Lucentis was approved in August 2012, and Eylea was approved in March 2015.

Breakthrough T1D played a critical part in clinical studies that led to their approval. A clinical trial of Lucentis (ranibizumab), funded by Breakthrough T1D and run by Quan Dong Nguyen, M.D., and Peter Campochiaro, M.D., demonstrated that this is an effective treatment for diabetic macular edema, with eyesight improving significantly for the 10 patients tested. They would go on to complete two clinical trials—READ 2 and READ 3—that showed substantial improvement in eyesight in people with diabetic macular edema treated with the drug.

In 2013, an estimated 90 percent of retinal specialists in the United States reported treating vision loss from diabetic macular edema with anti-VEGF therapy.

Through the Restoring Vision Moonshot, a special initiative of the Mary Tyler Moore and S. Robert Levine Charitable Foundation and Breakthrough T1D launched to honor Mary’s contributions to diabetes awareness and research, Breakthrough T1D is now supporting additional research to find new ways to prevent the development of diabetic retinal disease, arrest its progression to preserve visual function, and restore lost vision.

Ensuring eye complications research continues, and accelerating the finding of “cures” for low vision and blindness and preventive treatments for diabetic retinal disease is extremely important to Breakthrough T1D and our T1D community.

Leading researchers gathered, in person, for the annual meeting of the Advanced Technologies & Treatments for Diabetes (ATTD) Conference, which took place from April 27-30. There were more than 4,000 attendees from 100 countries attending, both in Barcelona and virtually, and featured more than 30 studies presented by Breakthrough T1D researchers, funded now or in the past, working to find cures for type 1 diabetes (T1D) and improve the lives of those living with the disease today.

Here are a few highlights:

• Results from the multi-center randomized insulin-only iLet bionic pancreas pivotal trial were presented by Steven Russell, M.D., Ph.D. The iLet system focuses on ease-of-use: Only a person’s weight is needed for initiation; the only setting to adjust is the glucose target; and mealtime announcements do not require carb counting. Those on iLet saw a +2.6 hour per day time-in-range improvement relative to the standard care group, improving from 51 percent at baseline to 65 percent at 13 weeks. In the iLet group, A1c fell from 7.9 percent at baseline to 7.3 percent at 13 weeks.

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.

• The findings from the InRange clinical trial were presented—the first-ever major industry-sponsored drug trial to use time-in-range as the primary outcome. Results, given by world-renowned scientists Richard Bergenstal, M.D., Thomas Danne, M.D., Tadej Battelino, M.D., Ph.D., Eric Renard, M.D., Ph.D., and Pratik Choudhary, M.D., Ph.D., found no significant difference in Toujeo (insulin glargine) and Tresiba (insulin degludec) users at 12 weeks using time-in-range. This is another step forward for the use of time-in-range and CGM metrics, and we look forward to hearing more on this front. (Go here if you want to read Breakthrough T1D’s position on time-in-range.)
• Stephanie Amiel, M.D., FRCP, a Breakthrough T1D grantee since she was a postdoc in the 1980s, presented results from the HARPdoc trial. The results, published in Nature Communications, showed that the behavioral health program HARPdoc did not reduce severe hypoglycemia compared to Blood Glucose Awareness Training (BGAT)—which was developed in the late 1980s—but it was superior to BGAT in reducing diabetes distress, depression, and anxiety, and these improvements in mental health were sustained over the entire duration of follow up.

The 2022 Insulin Centennial Award, a new initiative which aims to recognize the value and importance of continued innovation in diabetes, was given to Dr. Amiel. It was presented by Irl Hirsch, M.D., who praised Dr. Amiel for her major contributions to the care and quality of life for people with diabetes.

• Abbott, Ypsomed, and CamDiab announced a new partnership to develop an artificial pancreas system, using the Abbott FreeStyle Libre® 3 sensor, CamDiab’s CamAPS® FX mobile app, and Ypsomed’s mylife^TM YpsoPump®. The companies intend to complete development by the end of 2022 with commercial availability expected thereafter. This will be the first commercial system to come to market with an Abbott CGM.

Breakthrough T1D funding helped create the algorithm and pump for this partnership. The algorithm was developed by Roman Hovorka, Ph.D., who had several Breakthrough T1D grants from 2006 to 2019; it came to the UK market in 2020. Breakthrough T1D and Ypsomed have an ongoing pump development partnership as part of Breakthrough T1D’s Open-Protocol Automated Insulin Delivery System Initiative.

• Revital Nimri, D.Med., and Moshe Phillip, M.D., provided an update on the international consensus meeting on AID technology. Yet to be published, the consensus will recommend that artificial pancreas systems should be “considered” for and made available for all people with type 1 diabetes, especially those facing challenges with general glycemic management, hypoglycemia, and/or significant glycemic variability. The group also recommended that “all the payers (government and private) should reimburse/cover the AID systems along with initial and ongoing AID education and support for the management of T1D.” This is based on evidence that has repeatedly shown that AID provides greater time-in-range improvements than any other current technology.

It’s conference time! The next big conference is the American Diabetes Association 82nd Scientific Sessions, which will run from June 3-7 in New Orleans. Throughout it, Breakthrough T1D will be sharing updates, from the blog to interviews with key researchers and early-career scientists to a “Happy Hour” with CEO Aaron J. Kowalski, Ph.D. To stay updated, follow us on Facebook (@Breakthrought1dHQ) and X (@BreakthroughT1D).

Diabetes researchers from all over the world gather for the Advanced Technologies & Treatments for Diabetes (ATTD) Conference, which took place in-person (as well as online) on April 27-30 in Barcelona, Spain.

Many of the latest advances will be discussed, including research that Breakthrough T1D has funded to advance new breakthroughs and therapies for people with type 1 diabetes (T1D). In total, 32 researchers presenting are Breakthrough T1D-funded, either now or in the past, including our own Sanjoy Dutta, Ph.D., Breakthrough T1D’s Chief Scientific Officer, and Jeannette Soderberg, Ph.D., Breakthrough T1D’s Director of European Research, who will chair a Breakthrough T1D Session on the Utility of Patient-Reported Outcomes (PROs) in Therapy Development for T1D: Putting the End-User Upfront, which will feature renowned individuals from Tandem Diabetes Care, Novo Nordisk, Lexicon Pharmaceuticals, and ViaCyte.

Here are some more highlights of Breakthrough T1D-funded research that will be featured at the conference:

• Artificial Pancreas System Pivotal Trial: Results from the multi-center randomized insulin-only iLet bionic pancreas pivotal trial will be presented by Steven Russell, M.D., Ph.D., who 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.
  • Also in this Closed-Loop Updates Session are Breakthrough T1D-funded:
    • Ohad Cohen, M.D., who will talk about real world data to optimize automated insulin delivery (AID) devices;
    • Boris Kovatchev, Ph.D., whose algorithm led to the Tandem Control-IQ™ artificial pancreas technology, who will present on long-term, real-life use of closed loop control;
    • Roman Hovorka, Ph.D., who generated the CamAPS® FX artificial pancreas system, on the applicability of closed loop solutions to type 2; and
    • Revital Nimri, D.Med., and Moshe Phillip, M.D., two co-founders of the DreaMed Diabetes company, who will offer highlights from the international consensus meeting on AID technology.
• Time-in-Range vs. HbA1c: The findings from the InRange clinical trial comparing time-in-range with a continuous glucose monitor (CGM) to HbA1c will be presented by world-renowned scientists Richard Bergenstal, M.D., Thomas Danne, M.D., Tadej Battelino, M.D., Ph.D., Eric Renard, M.D., Ph.D., and Pratik Choudhary, M.D., Ph.D. I hope that this clinical trial confirms the use of CGM in clinical practice, as well as its application as an outcome measure in clinical trials. (Go here for a look at Breakthrough T1D’s position on time-in-range, which is a potentially better tool than A1c.) Stay tuned for the results.
• Exercise + T1D: Clinical trial results, funded by Breakthrough T1D, will be presented by Peter G. Jacobs, Ph.D., investigating the use of an artificial pancreas system that responds automatically to physical activity, using the iPancreas system developed by the Oregon Health & Science University. Preliminary results from the T1D Exercise Initiative (T1Dexi) will be presented by Michael C. Riddell, Ph.D., which should help researchers learn more about the effect of exercise on blood sugar and its role in artificial pancreas technology.

You’ve seen the ads: Victoza®. Ozempic®. Trulicity®.

They are for type 2 diabetes, and they lower your blood-sugar levels and cause the majority of people who use them to lose weight. And they can lower your risk of major cardiovascular events, such as heart attack and stroke.

But did you know that these drugs came about, in part, because of type 1 diabetes (T1D) research?

In honor of the 100th anniversary of the first administration of insulin, Breakthrough T1D launched “100 Years, 100 Breakthrough T1D Scientists,” to tell the story of scientists and their discoveries, which put together the vast knowledge that we have about diabetes today.

The next one: GLP-1 treatments.

Cloning the Hormone Glucagon

You read about the cloning and expression of insulin in our latest “100, 100,” but it does not stop with insulin. When she was a postdoctoral fellow working in the laboratory of Joel Habener, Ph.D., Pauline Kay Lund, Ph.D.—who would go on to receive a 1982-1985 Breakthrough T1D Career Development Award—was the first to clone the hormone glucagon and discover two new hormones: glucagon-like peptide 1 (GLP-1) and 2 (GLP-2).

Said Lund, in an interview published in the Autumn 1985 issue of Countdown: “By understanding the factors which regulate glucagon gene activity and the production of glucagon, GLP-1, and GLP-2, it should be possible to predict the dietary and hormonal influences which best produce normal regulation of plasma glucose. This will aid in development of preventive and therapeutic measures to produce normal glucose regulation in patients with diabetes.”

In other words, understanding the protein could lead to the development of drugs that can help you reach a better blood-sugar range for people with diabetes.

Subsequent work revealed that GLP-1 encourages the release of insulin from the pancreas and reduces the release of glucagon, and clinical trials demonstrated that it was effective in treating type 2 diabetes.

In 2005, the FDA approved Byetta (exenatide). There are now seven GLP-1 medicines on the market.

Breakthrough T1D Leadership

Breakthrough T1D funded copious research in the 1980s and 1990s to understand the role of glucagon and glucagon-like peptide 1 in type 1 diabetes, including:

• Patricia Brubaker, Ph.D., during her Breakthrough T1D-funded postdoctoral fellowship in the laboratory of Mladen Vranic, M.D., D.Sc., between 1982-1985.
• She would stay at the University of Toronto, working with Daniel Drucker, M.D., who held a Breakthrough T1D grant from 1992-2009, on GLP function and development.
• Louise Scrocchi, Ph.D., was a Breakthrough T1D-funded postdoctoral fellow in the laboratory of Dr. Drucker, from 1996-1998, when she demonstrated the critical role of GLP-1 as an incretin hormone.

And there are many more Breakthrough T1D investigators who had a hand in making this new class of agents a reality to the diabetes community.

Breakthrough T1D Clinical Trials

When GLP-1 treatments came out, everyone in the type 1 space wanted to know if it worked for type 1 diabetes. Breakthrough T1D and others funded a number of clinical trials testing it with insulin, to see if it improved outcomes. Unfortunately, although it reduced HbA1c and total insulin dose, it increased the rates of low blood sugar (called hypoglycemia) and high blood sugar (hyperglycemia) events, thereby limiting its clinical use.

In the past few years, however, we have started to wonder whether three drugs (insulin + 2 other drugs) might work, and are now funding a trial to see if a GLP-1 therapy (semaglutide, brand name Ozempic, Rybelsus) and an SGLT therapy (dapagliflozin, brand name Farxiga), taken with insulin, can reach better blood sugar levels, compared with a dual therapy or insulin only.

Results won’t be out for another year or two, but stay tuned.

[1] Lund PK, Goodman RH, Habener JF. Intestinal glucagon mRNA identified by hybridization to a cloned islet cDNA encoding a precursor. Biochem Biophys Res Commun 1981; 100: 1659-1666. PMID: 7028035.

[2] Lund PK, Goodman RH, Habener JF. Pancreatic pre-proglucagons are encoded by two separate mRNAs. J Biol Chem 1981; 256: 6515-6518. PMID: 6165720.

[3] Lund PK, Goodman RH, Dee PC, Habener JF. Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem. Proc Natl Acad Sci USA 1982; 79: 345-349. PMID: 7043459 PMCID: PMC345726.

[4] Lund PK, Goodman RH, Montminy MR, Dee PC, Habener JF. Anglerfish islet pre-proglucagon II. Nucleotide and corresponding amino acid sequence of the cDNA. J Biol Chem 1983; 258: 3280-3284. PMID: 6338015.