“Our Trials are Totally Different.” The Denise Faustman Interview

There’s no question that Dr. Denise Faustman does things differently.

Dr. Faustman’s research has won her avid fans and raised millions from donors, but it has also provoked significant pushback from major diabetes organizations. Dr. Faustman wears that repudiation like a badge of honor, proof that her work is disruptive and important.

A Maverick Approach

Dr. Faustman takes an unconventional approach. Her work, which is focused on the underlying immune response responsible for type 1 diabetes, has led her to a very old and inexpensive drug, a tuberculosis vaccine used widely in the developing world. It’s a treatment that may have been hiding in plain sight for generations.

Dr. Faustman’s immune intervention trials also concentrate on adults with long-standing type 1 diabetes. By contrast, virtually all of her peers have targetted patients with new-onset diabetes, or even patients that have yet to develop diabetes. This approach is generally considered more likely to succeed, because the targets of the interventions have not yet entirely lost their ability to secrete insulin. But in Dr. Faustman’s telling, it hasn’t accomplished much yet:

“Over the last 30 years, immune intervention trials in type 1 diabetes haven’t had very good outcomes. The important diabetes advances have been different versions of insulin and new forms of blood testing, but the immune intervention trials have been a very sad point. Nothing’s worked very well, no new treatments have been approved.”

“Our trials are totally different. They’re all in people that have had diabetes for decades.”

Dr. Faustman told me that a who’s who of diabetes experts has told that her approach is crazy, a response that has clearly tickled her contrarian side.

“We thought the need is to treat the people that actually have the disease. It sounds like a no-brainer, but keep in mind that nobody else is doing it!”

The decision to study patients with long-established diabetes, which was originally made well over a decade ago, was inspired in part by financial constraints: “we could not afford to do new-onset diabetic trials.” And focusing on an incredibly inexpensive generic drug meant that Dr. Faustman had no way of interesting large pharmaceutical companies and their very large R&D budgets.

“It’s a terrible drug to make money off of.”

BCG

The drug is BCG, the Bacillus Calmette–Guérin vaccine, which was first used a century ago in order to protect patients from tuberculosis. It is considered extremely safe, and is still administered to millions of infants annually, most prominently in the developing world.

BCG first piqued Dr. Faustman’s interest because it was “the only drug in animal models that has worked in established diabetic mice.” Exactly why it worked, though, still requires some unraveling. The results of her Phase I trial – results that were both celebrated and questioned – showed that patients receiving the vaccine experienced impressive improvements in glucose control without restoring insulin production or insulin sensitivity.

Most immune intervention drug trials involve the suppression of immune cells that are harming the body – in the case of type 1 diabetes, the T-cells that attack the pancreatic Beta cells. But the BCG vaccine works the opposite way, not by depleting the immune system, but by putting something else back in.

“BCG adds to the microbiome. It’s actually the tuberculosis organism, inactivated. So you’re putting back in, effectively, tuberculosis. When you revaccinate with this vaccine, the reason it takes a little while is that it gets to your bone marrow and actually resets your stem cells in your bone marrow.”

Why would you want tuberculosis in your bone marrow? Dr. Faustman referred to the hygiene hypothesis, the idea that many autoimmune and allergic diseases are caused at least in part by our excessively sanitary modern world. Myobacterium tuberculosis may have co-evolved with humans for thousands of years, and its absence may therefore trigger immune system dysfunction.

“The absence of this organism has allowed these rogue immune systems to take off and create all these autoimmune diseases. We’re just reestablishing this synergistic relationship to get immune tolerance.”

Because of its many possible effects, BCG has lately become “fashionable” in the research community, Dr. Faustman told me. The old vaccine is being evaluated as a treatment for other serious autoimmune diseases, and it has also been theorized to provide protection against the novel coronavirus that causes COVID-19.

But how does all that help with your blood sugar levels? Dr. Faustman believes that when BCG vaccine “retrains” the immune system, it also causes the immune system itself to begin utilizing large amounts of glucose in the bloodstream.

“What really happens is that their white blood cells now become the regulator of sugar, and have restored sugar transport. So there are underlying defects in type 1 diabetes in the use of the lymphoid system as a sugar regulator, and BCG restores that.”

The Effect

“It’s definitely a game-changer. Our hope, based on the early results, is that it will lower your A1c 10-15%, stably. You can use less insulin, and have better blood sugar control.”

It is, however, a slow process:

“It takes a number of years to have its metabolic and immune effects. We know we need to follow these patients for 3-5 years to get the maximal effect. But it’s got good durability. It’s quite permanent.”

The nine patients that originally received the BCG vaccine for the Phase I trial are still checking in with Dr. Faustman’s lab every six months, and she says that they continue to enjoy dramatic improvements in glucose management.

“Everyone wants to know if we have any [trial participants] off insulin. We have one person off insulin. Normally when he’s on a fairly low dose of insulin his A1c is in the normal range. When he goes off insulin, he no longer goes into DKA, but he goes up to around 7.2%.

“Is it gonna last twenty years? Thirty years? We don’t know yet.”

Sample Size

One of the chief concerns that other experts have raised with Dr. Faustman’s work is the tiny sample used in her Phase I trial: a mere nine patients received the BCG vaccine.

Dr. Faustman is completely unphased by this criticism, arguing that the statistical significance of her results speaks for itself.

“A p-value of .05 is as statistically significant in a sample of 10 as it is in a sample of 200,000. The only difference is, in the sample of 10, everybody responded, and the magnitude of the response was large.

“If you have to design big trials, you have small effects and unresponsive groups. And that’s what you’re seeing in the [rest of the] diabetes community.”

The criticism of her work by major diabetes authorities, particularly ADA and JDRF, doesn’t seem to have phased her, although she admits that it has slowed down the pace of her trials. She quoted one of her most significant boosters, the late Lee Iococca, a rockstar among American executives as the CEO of Chrysler during the 1980s. Iacocca told her, “I love it when they’re shooting the cannons at me. It means I’ve got something good.”

Dr. Faustman continued: “If they didn’t think it was competitive, it wouldn’t matter to them. The fact that they shot their cannons, to issue statements that were not truthful, it shows that it mattered to them a lot, that it was threatening to them.” She believes that the criticism set forth by the ADA and JDRF in a remarkable joint letter was not only misguided but dishonest.

Don’t Do It Yourself

Referring to the BCG vaccine’s long history of safety, Dr. Faustman suggested that there was little downside to her proposed intervention.

I felt an uncomfortable comparison to some of the pandemic era’s health controversies, in particular to the arguments advanced by many in favor of poorly investigated COVID-19 treatments such as hydroxychloroquine and ivermectin. I asked her what she would say to readers that are ready to go get the BCG vaccine themselves, before it’s been evaluated by the FDA. It’s a question she deals with constantly.

About once a month, Dr. Faustman gets a call from a physician, asking confidentially where one might acquire BCG of the correct strain. Sometimes it’s pharmacies attempting to fulfill a prescription, sometimes it’s the patients (or parents) themselves.

“Everyone’s trying to do it in the closet because it’s a safe drug, right? People try to do it all the time. But you should really wait until we get the right strain and the dosing. What we try to say is that if you get vaccinated with the wrong strain of BCG, we’re not sure, when we give you the right strain, that it’s gonna work.”

The BCG vaccine may be easy to come by in countries where it is used frequently, but there’s no telling what strain you’d get and what the effects would be.

For patients that are very eager about BCG, Dr. Faustman recommends registering for one of her clinical trials.

Timeline to Treatment

There’s already a phase II trial underway, which will test the BCG vaccine in adults with long-standing type 1 diabetes. This expands the study size from 9 to over 200; Dr. Faustman expects that good results in a much larger cohort will finally resolve the criticism and controversy that has dogged her for years.

Meanwhile, her lab is beginning its first trial of children with type 1 diabetes.

In an ideal world, she told me, the phase II trial for adults would be followed by phase III, an even larger study which she would then present to the FDA for evaluation. In a best-case scenario, the approved drug could be administered to regular patients in “five to eight years.”

“We’re moving as fast as we can.”

Source: diabetesdaily.com

Islet Cell Transplants: How the USA Fell Behind the Rest of the World

The United States has fallen behind other countries in the effort to make pancreatic islet cell transplants available for patients with type 1 diabetes. As the technique grows in popularity through much of the developed world, in America innovation has come to a standstill.

Islet transplantation is an advanced treatment for type 1 diabetes. Briefly, doctors take a donor’s islets of Langerhans (the clusters of cells in the pancreas that contain the insulin-producing beta cells) and inject them into patients with diabetes, typically into the liver. When successful, patients can discontinue insulin use altogether, or greatly reduce it. Some transplant recipients have remained free of insulin therapy for many years following the procedure, with only minor side effects, although most patients require some insulin therapy at five years post-transplant.

Islet cells are harvested from the pancreas of a deceased organ donor, and immunosuppressive drugs are required to prevent rejection by the recipient’s immune system. These donor cells are scarce, and while there are many ongoing attempts to find other sources of usable islet cells (such as the use of pluripotent stem cells or even genetically engineered pigs), the procedure is not expected to become a mainstream treatment in the foreseeable future. But for patients with a dire need—for example, those with extreme glucose management challenges, hypoglycemia unawareness, or advanced kidney disease—islet transplantation can be a lifesaver.

Unfortunately, in the United States, the procedure has been “effectively halted,” according to an official report on the American Diabetes Association’s recent Scientific Sessions conference. While the technique was largely investigated and defined by scientists working in the US, it has never become available to the general public, and there is little hope that it will become available any time soon. Meanwhile, some medical centers in Canada, Australia, Europe, and Asia are now performing the technique routinely.

Dr. Camillio Ricordi, a leading researcher on the treatment with the University of Miami, blamed the issue on “outdated regulation” from the FDA. Because of a quirk in the National Organ Transplant Act of 1983, subparts of organs (such as the islets of Langerhans) don’t count as organs and are not covered by the network of rules and programs governing organ transplantation. Instead, transplanted islet cells are regulated as if they were drugs. Treating the cells as pharmaceuticals subjects them to standards for precision and consistency that they cannot meet.

Phase 3 trials have already proved that islet cell transplantation can deliver impressive results, and do so safely. And yet, America’s leading experts have agreed that it is all but impossible for a research institution to apply for and secure full approval for the technique.

Around the world, other medical authorities have taken a more practical stance. This has also allowed insurers to pay for the procedure, just as they would any other organ transplant. Most of the countries that lead the world in islet transplantations have robust social healthcare systems.

But islet transplantation is still considered purely experimental in the United States, and today can only be performed under the auspices of an official clinical trial. While the ADA and other advocates have pushed for change, so far, the regulation still stands in the way.

As islet transplantation becomes more available across the globe, the treatment is going nowhere fast in the USA.

 

Source: diabetesdaily.com

Tackling Type 1 Diabetes – Where Are We on Technology and Research?

This content originally appeared on diaTribe. Republished with permission.

By Andrew Briskin

Andrew Briskin joined the diaTribe Foundation in 2021 after graduating from the University of Pennsylvania with a degree in Health and Societies. Briskin is an Editor for diaTribe Learn.

At the Milken Institute 2021 Future of Health Summit, leading experts in type 1 diabetes research and innovation discussed the path toward a cure, the latest in glucose monitoring technology, and the importance of screening for type 1 diabetes.

A group of leading experts in type 1 diabetes research and innovation took part in the panel discussion, “Tackling Type 1 Diabetes: Where the Science is Heading” at the Milken Institute 2021 Future of Health Summit last month. They exchanged insights on the advantages of continuous glucose monitoring, automated insulin delivery (AID), Time in Range for better diabetes management, as well as tantalizing new possibilities for curing type 1 diabetes.

The discussion from June 22nd was moderated by diaTribe Founder Kelly Close and included:

  • Aaron Kowalski, Ph.D. – CEO, JDRF International
  • Shideh Majidi, M.D. – Assistant Professor, Pediatric Endocrinology, Barbara Davis Center for Diabetes
  • Felicia Pagliuca, Ph.D.  – Vice President and Disease Area Executive, Type 1 Diabetes, Vertex Pharmaceuticals
  • David A. Pearce, Ph.D. – President of Innovation, Research and World Clinic, Sanford Research

The panelists began by discussing how continuous glucose monitors (CGM) now provide people with type 1 diabetes even more information and the power to manage their glucose levels. CGM data provides people with crucial metrics such as Time in Range (TIR), which corresponds to the percent of time someone spends within their target glucose range – usually 70 to 180 mg/dL. This target glucose range may vary though, for example, if you are pregnant. You can learn more about the helpful metrics that CGM provides here. Alongside A1C, TIR allows more insight into your day-to-day diabetes management by showing fluctuations in glucose levels caused by factors like meals, exercise, illness, and more.

However, CGM is not perfect or widely accessible yet. The panelists touched on this issue of access to CGM and the existing disparities in care across race and type of insurance. Dr. Majidi emphasized that in populations with access to this technology, CGM use has increased from 20% to over 80% of patients over the last five years. However, some studies have shown that providers tend to prescribe technology only to certain patients due to unconscious biases about which patients may be able to handle using advanced technology.

Advocating for early and consistent training for healthcare providers on addressing these biases, as well as provider and patient education on CGM and other technologies for glucose management, Dr. Majidi said, “we need to look at these unconscious biases to start providing everyone with the opportunity to use and learn about new technology.”

The panel then explored the advantage of AID hybrid closed-loop systems. These systems combine a CGM, insulin pump, and an algorithm that allows the CGM and insulin pump to talk to each other. Dr. Kowalski said he was especially encouraged by the advancements in AID systems, emphasizing that it not only decreases the number of highs and lows, but it also removes much of the burden of diabetes management from patients and their families.

AID systems especially benefit families with children who have diabetes, reducing concerns from parents about the safety of their children during the night or at other times when the risk of hypoglycemia is high. The panelists said they were hopeful that these new innovations are bringing us closer to developing a fully closed-loop artificial pancreas, which could automatically respond to changes in glucose in real time without the need for a person to deliver manual boluses or calibrations.

Echoing their advice on how to address disparities in CGM use, the panelists noted the importance of education for healthcare providers to combat disparities in prescribing AID to ensure equal opportunity for all to achieve better health outcomes.

The discussion then shifted to the latest research towards a cure for type 1 diabetes, focusing on beta cell replacement therapies. Because type 1 diabetes occurs as a result of the body’s immune system attacking and destroying its own pancreatic beta cells (the cells that make insulin), scientists have been researching how to replenish the beta cell population from stem cells. Scientists believe that stem cells, not yet fully differentiated or mature cells, could potentially be directed to become functioning beta cells.

Dr. Pagliuca shared updates from her work at Vertex, studying stem cell-derived beta cell transplants in type 1 patients with impaired awareness of hypoglycemia. This initial study relies on systemic immunosuppressive drugs (these are drugs that “turn off” the body’s immune system so it won’t attack the implanted cells) to protect the implanted beta cells. The hope is that future studies will seek to use a different method called encapsulation, which protects beta cells from the immune system with a physical barrier, avoiding the need for immunosuppressant medications.

So far, with the successful conversion of stem cells into mature beta cells accomplished in controlled lab settings, the science has developed to the point of testing stem cell-derived beta cells in clinical trials, with Vertex first clinical trial now enrolling patients. This initiative will encompass the entire type 1 community, with Dr. Pagliuca stressing that “transitioning these breakthroughs into the clinical phase will require participation from all stakeholders, patients, researchers, and healthcare providers.”

Considering the latest research into the immunobiology of type 1 diabetes, the panelists advocated for significant increases in screening for type 1 across the general population.

Dr. Pearce advised that testing for the presence of specific autoantibodies (small molecules in the body that are the cause of the immune system attacking a person’s own beta cells) in the general population is essential for implementing prevention programs, given that the presence of at least two of these autoantibodies is a very predictive measure to assess the risk of developing type 1 diabetes.

According to him, the predictive power of these screenings make it is possible to classify an individual as having type 1 diabetes years in advance of any symptoms, even while they still have normal glycemic control. In this way, type 1 diabetes can be classified into 3 stages – stage 1 is when someone has two or more diabetes-associated autoantibodies, but normal glycemia and no symptoms. Stage 2 is when you have the autoantibodies, have begun to develop glucose intolerance or abnormal glycemia, but still no symptoms. Stage 3 is when symptoms begin and you are diagnosed with type 1 diabetes. Classifying diabetes in this way and identifying those in the early stages could increase patient involvement in clinical trials, and help connect individuals to new drugs such as teplizumab (not yet approved by the FDA), that aim to delay the onset of symptomatic type 1 diabetes or prevent it altogether.

Drs. Pearce and Kowalski agreed, recommending a screening strategy involving primary care providers and screening children during the toddler years. On the importance of this screening process for involvement in clinical trials, Dr. Kowalski noted, “Diabetes is a global problem. The voice of the patient is hugely important on new devices and therapies, and clinical trial pathways are delayed when there isn’t equal participation in the trials.”

You can watch the panel discussion and hear insights from the four incredible experts here.

Source: diabetesdaily.com

Should We Be Screening Every Single Child for Type 1 Diabetes Risk?

If Type 1 diabetes struck you or a family member, it may well have seemed completely random, unpredictable, and unpreventable.

It’s less random than it might seem—with a drop of blood, doctors can roughly estimate the risk of developing the condition, even in a newborn baby. And while the condition cannot yet be prevented, education and awareness can make its onset significantly less damaging, possibly resulting in lifelong health gains.

Screening for type 1 diabetes risk could become a routine element of childhood checkups, applied to all children. Should it be?

How Screening Works

There are, generally speaking, two ways of screening for type 1 diabetes risk.

The first, autoantibody screening, tests the blood for the immune proteins that cause type 1 diabetes when they attack the pancreas’ Beta cells. Autoantibodies emerge unpredictably, and are best assessed in early childhood, when the risk of disease onset is at its highest.

The second, genetic screening, tests a patient’s DNA for variations that are associated with type 1 diabetes. Genetic screening can be accomplished immediately after birth.

Screening of either sort rarely gives a definitive answer as to the likelihood that any one person will or will not develop type 1 diabetes—it places a patient in a bracket of higher or lower risk. One exception is when a blood test finds multiple autoantibodies present in one person, which can be said to indicate very early (subclinical) type 1 diabetes. In these cases, it may be years before the symptoms become noticeable.

Much of the data linking antibody presence with risk factors comes from the long-running Trialnet Pathway to Prevention study. TrialNet has been celebrated in the diabetes community for providing simple and free screening to so many. Click the link, and you can contribute to the body of knowledge by getting yourself (or a family member) screened.

Genetic and autoantibody screening can be used separately, but the most accurate projections use the two (along with any family history of diabetes) in concert.

The Benefits of Screening

Type 1 diabetes isn’t, so far as we know, preventable. So why screen for it at all?

Perhaps the single largest benefit to type 1 diabetes screening is the reduced incidence of diabetic ketoacidosis (DKA). When doctors, patients, parents, and caregivers are all aware that one patient has an increased risk, they’ll be more likely to identify hyperglycemia early, before it progresses to a critical state.

Avoiding DKA, a dangerous and incredibly painful condition, is just the start of it: studies have also shown that patients that got an early warning of the risk of type 1 diabetes also go on to have reduced A1c, fewer diabetes symptoms, and increased residual beta cell functioning. The earlier you catch the progression of type 1 diabetes, the healthier you’re likely to be in the coming years and perhaps even decades.

While researchers can’t always prove a causal relationship, mounting evidence appears to show that the severity of hyperglycemia at diagnosis can have a lasting and possibly even lifelong effect. In our recent article on diabetes and the brain, for instance, we learned that children that experience severe DKA at diagnosis have measurably worse cognitive impairment compared to children that did not have DKA. This effect lasts for years, and may be permanent.

And then there’s the game-changing drug teplizumab, which appears to delay the progression of symptomatic diabetes for years when given to patients that already have two or more antibodies. Those delays can be hugely valuable to families, meaning both enhanced health and emotional well-being. An expert panel recently voted to recommend that the FDA approve the drug. If teplizumab proves to be as effective as hoped, it would significantly strengthen the case for large-scale type 1 diabetes risk screening.

Teplizumab may just be the start, as doctors are working on other novel approaches to delaying (or preventing) type 1 diabetes. At the moment, for example, trials are underway to see if infants with a genetic predisposition to the condition will be less likely to develop the disease if given the probiotic B. infantis or insulin powder. Who knows what other therapies the future could bring?

Experiments with Universal Screening

At the recent American Diabetes Association Scientific Sessions, Germany’s Dr. Anette-Gabriele Ziegler discussed the results of two different experiments in universal diabetes screening. In these studies, all children within a certain area were tested for type 1 diabetes antibodies, regardless of family history.

The first, named the Fr1da study, tested children aged 2-5 during their regular check-ups in Bavaria, Germany. Only 0.29% of these Bavarian children got the bad news that they had the antibodies indicating subclinical type 1 diabetes.

While this was a very thin slice of the population, that knowledge still made a big difference. 81 tested Bavarian children went on to develop full-blown type 1 diabetes within the next three years; of those 81, only three developed DKA, an astoundingly low 3.7%. This was an immense improvement over the status quo – elsewhere in Germany, about 45% of newly diagnosed children developed DKA. And even that 3.7% seems somewhat inflated – of the three kids that suffered DKA, two of them belonged to families that declined diabetes education after receiving the positive test results.

In short, testing about 140,000 kids saved about 36 (and counting) from DKA and from whatever other long-term health deficits that acute hyperglycemia might have caused in the future. It also significantly reduced stress in the parents of newly diagnosed children.

A similar effort in Colorado, named ASK, delivered similar results. While only 0.52% of the participants were found to have subclinical type 1 diabetes, only 6% of them developed DKA, a vast improvement over usual rates.

Dr. Ziegler said, “We would like to screen everybody.”

The Downside of Screening Too Many

So why not start screening every child now? It costs money. Insurance companies will need to be convinced that it’s worth paying for.

The cost of screening may be significant, and the cost of follow-up education can be even higher.

Even if we can screen all children for type 1 diabetes, it’s not at all clear how many families should receive diabetes education, as Dr. Richard Oram of the UK’s University of Exeter expressed in a presentation at the conference.

Suppose, for example, that we had a universal genetic testing program – every newborn child in the country gets his or her drop of blood analyzed. At what level of genetic risk do you begin to apply education and intervention?

If you draw the line at the infants in the top 10% highest risk, you’ll identify nearly 80% of the kids that are going to develop type 1 in the coming years … but that’s only 2.4% of the kids selected for extra attention, meaning it’s likely a waste of time for the remaining 97.6%. On the other hand, if you only choose to educate the tiny minority of kids with the highest risks, you’ll waste less time, but ultimately only identify less than 10% of the children that will go on to develop type 1.

Public health experts are not ready to just brush aside all that education delivered to families that don’t really need it. And it’s not just a question of wasted time or money – as noted by Dr. Laura Smith, a clinical psychologist at USF, studies have shown that these screening programs can result in clinically significant levels of stress or anxiety for kids and caregivers alike. Parents will also often attempt to change their kids’ diets or increase their monitoring of their kids’ health, perhaps unnecessarily.

Profit and Loss

In reality, it will likely be the insurance companies that decide where to draw the line. The most important question, sad as it sounds, is whether or not testing children for type 1 diabetes risk is cost-effective.

Early research into this question tended to say that no, broad screening efforts are not economically worthwhile. A 2015 study concluded that screening would have to cost $1 or less in order to be viable (it’s a lot higher)—anything more would cost too much to justify the health improvements.

That study, however, looked only at the impact of reduced incidence of DKA, and not at the other benefits for patients. The University of Colorado’s Dr. R. Brett McQueen argued to the Scientific Sessions audience that this early study fell short of the mark, because screening is likely to offer many benefits beyond just DKA avoidance.

Dr. McQueen presented his own study, which assumed that screening would result in lifelong health improvements for patients with new-onset type 1 diabetes, such as improved A1c. While McQueen’s work confirmed that DKA avoidance alone was not enough to justify the high cost of most screening programs, those other benefits may tip the scales. Even an extremely modest improvement in glycemic control can make a big difference over the years, leading to many fewer diabetic complications and expensive interventions. And that’s before we even consider teplizumab, the potentially groundbreaking therapy that can delay onset for years.

The cost of screening is certainly substantial – Colorado’s ASK screening program ended up spending about $4,700 per case detected, a number that could be even higher when implemented elsewhere. But DKA and diabetes complications—think retinopathy and kidney disease—are pretty expensive too.

This type of math requires some guesswork. McQueen stated that if we want a rigorous accounting of how cost-effective early screening is likely to be, we’ll need about 30 years of follow-up data. Of course, we don’t have the luxury to sit back and wait for generations—“we need to make these decisions now.”

Conclusion

Today there is virtually no screening for type 1 diabetes risk factors in mainstream medical practice. There are many children (millions worldwide) that are at an enhanced risk of developing type 1 diabetes, and would stand to benefit from diabetes awareness and education.

Screening (and follow-up education) can have a significant positive effect. Risk screening has been shown to dramatically reduce the incidence of DKA, and is likely to improve diabetes management and reduce stress and anxiety. And the recent development of teplizumab, a drug that can delay the onset of the disease, may make early screening even more efficacious.

The most accurate screening would combine genetic testing at birth with antibody testing in early childhood, either once at age 3-4, or twice, at ages 2-3, and again at 5-7. But even a single test, either of genetics or autoantibodies, can provide significant predictive value.

Screening for type 1 diabetes risk could become a routine element of childhood checkups—if doctors and insurers can be convinced that it’s worth the effort, time, and money.

Source: diabetesdaily.com

Insulin at 100, Part 3: Insulin’s Uncertain Future

This content originally appeared on diaTribe. Republished with permission.

This is Part 3 of James S. Hirsch’s exploration of the riveting history of insulin, on the occasion of its 100th birthday.

Part 1: The Discovery

Part 2: Failed Promises, Bold Breakthroughs

Insulin’s Uncertain Future

Insulin

Image source: Emily Ye, Diabetes Daily

As further refinements in insulin occurred, the insulin narrative should have become even more powerful – that insulin not only saves people, but in reaching new pharmacological heights, it is allowing patients to live healthier, better, and more productive lives. These should be insulin’s glory days – as well as days of unprecedented commercial opportunity. According to the International Diabetes Federation, in 2019, the global population of people with diabetes had increased a staggering 63 percent in just nine years – to 463 million patients.

Insulin sales should be booming, with a new generation of Elizabeth Evans Hughes and Eva Saxls to tell the story. In fact, insulin sales are declining, and insulin has no spokespeople. Reasons vary for these developments, but one fact is undeniable: insulin has lost its halo.

Insulin is still essential for any person with type 1 diabetes, though even with type 1 patients, insulin is sometimes under-prescribed as doctors fear getting sued over a severe hypoglycemic incident. The belief is that patients are responsible for high blood sugars, doctors for low blood sugars.

Where insulin has lost its appeal is with type 2 patients, which has driven the diabetes epidemic in the U.S and abroad. According to the CDC, from 2000 to 2018, America’s diabetes population surged 185 percent, from 12 million to 34.2 million, and an estimated 90 percent to 95 percent of that cohort has type 2. (The global percentage is similar.) These patients have long had options other than insulin – metformin, introduced in 1995, remains the ADA’s recommended first-line agent. But as a progressive disease, type 2 diabetes, in most cases, will eventually require a more intensive glucose-lowering therapy. Nothing achieves that objective better than insulin, but insulin is delayed or spurned entirely by many type 2 patients.

Some concerns are longstanding; namely, that insulin can lead to weight gain because patients now retain their nutrients. Some type 2 patients wrongly associate insulin with personal failure surrounding diet or exercise, so they want to avoid the perceived stigma of insulin. Some people just don’t like injections. Meanwhile, other patients associate insulin with the medication that an ailing patient takes shortly before they die: insulin as a precursor to death. Some clinicians who care for Hispanic patients refer to insulin pens as las plumas to avoid using a word that carries so much baggage.

What’s striking is how dramatically the cultural narrative has changed, from insulin the miracle drug to insulin the medical curse. And where are the commercials, the movies, the documentaries, and the splashy publicity campaigns about the wonders of insulin? They don’t exist.

The greatest impact on insulin use in type 2 diabetes has been the emergence of a dozen new classes of diabetic drugs. These include incretin-based therapies known as GLP-1 agonists and DPP-4 inhibitors (introduced in the 2000s) as well as SGLT-2 inhibitors (introduced in 2014). diaTribe has covered these therapies extensively, and their brands are all over TV: Trulicity, Jardiance, Invokana, and more. They all seem to have funky names, and like insulin, they can all lower blood sugars but – depending on which one is used – some have other potential advantages, such as weight loss. (Some have possible disadvantages as well, including nausea.)

The expectations for these drugs were always high, but what no one predicted was that GLP-1 agonists and SGLT-2 inhibitors have been shown to reduce the risk of both heart and kidney disease – findings that are a boon to type 2 patients, who are at higher risk of these diseases. These findings, however, were completely accidental to the original mission of these therapies.

Insulin, the miracle drug, has been eclipsed by drugs that are even more miraculous!

Consider Eli Lilly, whose Humalog is the market-leading insulin in the United States. In 2020, Humalog sales fell 7 percent, to $2.6 billion, while Trulicity, its GLP-1 agonist, saw its sales increase by 23 percent, to $5 billion.

That’s consistent with the global insulin market. Worldwide insulin sales in 2020 declined by 4 percent, to $19.4 billion, marking the first time since 2012 that global insulin sales fell below $20 billion.

It’s quite stunning. Amid a global diabetes epidemic, and with the purity, stability, and quality of insulin better than ever, insulin sales are falling. (Pricing pressures from insurers and government payers have also taken a revenue toll.) In 2019, Sanofi announced that it was going to discontinue its research into diabetes, even though its Lantus insulin had been a blockbuster for years. More lucrative opportunities now lay elsewhere.

Falling sales may not be the insulin companies’ biggest problem. Public scorn is. Though the insulins kept getting better, the prices kept rising, forcing many patients to ration their supplies, seek cheaper alternatives in Canada or Mexico, or settle for inferior insulins. Some patients have died for lack of insulin. According to a 2019 study from the nonprofit Health Care Cost Institute, the cost of insulin nearly doubled for type 1 patients in the United States between 2012 and 2016 – they paid, on average, $5,705 a year for insulin in 2016, compared to $2,864 in 2012.

Many patients are outraged and have used social media to rally support – one trending hashtag was #makeinsulinaffordable. Patient advocates have traveled to Eli Lilly’s headquarters to protest. In March of this year, nine Congressional Democrats demanded that the Federal Trade Commission investigate insulin price collusion among Eli Lilly, Novo Nordisk, and Sanofi, asserting they “are using their stranglehold on the market to drive up costs.” The letter notes that as many as one in four Americans who need insulin cannot afford it, and at least 13 Americans have died in recent years because of insulin rationing.

The criticism has been unsparing. In April 2019, in a hearing for the U.S. House of Representatives on insulin affordability, Democrats and Republicans alike pilloried the insulin executives. At one point, Rep. Jan Schakowsky (D-Illinois) said to them, “I don’t know how you people sleep at night.”

Insulin is hardly the only drug whose price has soared, but as the Washington Post noted last year, insulin is “a natural poster child of pharmaceutical greed.”

In response, the insulin companies have adopted payment assistance programs to help financially strapped consumers. They also blame the middlemen in the system – the PBMs, or the Pharmaceutical Benefit Managers – for high insulin prices, who in turn blame the insulin companies, and everyone blames the insurers, who point the finger at the companies and the PBMs.

Drug pricing in America is so convoluted it’s impossible for any patient to accurately apportion blame, but the history of insulin explains in part why the companies have come under such attack. When Banting made his discovery, he sold the patent to the University of Toronto for $1. He said that insulin was a gift to humankind and should be made available to anyone who needs it. Insulin was always profitable for Eli Lilly and the few other companies who made it, and critics have complained that the companies found ways to protect their patents by making incremental improvements in the drug.

But for years, those complaints were easily dismissed. The companies were revered for their ability to mass produce – and improve – a lifesaving drug that symbolized the pinnacle of scientific discovery while doing so at prices that were affordable.

When prices became unaffordable – and regardless of blame – the companies were seen as betraying the very spirit in which insulin was discovered and produced, and their fall from grace has few equivalents in corporate history.

Is the criticism fair?

Hard to say, but even the companies would acknowledge that they’ve squandered much good will. Personally, I’m the last person to bash the insulin companies – they’ve kept me and members of family alive for quite some time. Collectively, my brother, my son, and I have been taking insulin for 117 years, so I feel more regret than anger: regret that at least one insulin executive didn’t stand up and say loudly and clearly:

“Insulin is a public good. No one who needs it will be without it. And we will make it easy for you.”

Insulin

Image source: Emily Ye, Diabetes Daily

Whatever that would cost in dollars would be made up for in good will – and such a public commitment would honor the many anonymous men, women, and children, before 1921 and after, who gave their lives to this disease.

The next chapter for insulin? It will almost certainly include continued improvements. Both Eli Lilly and Novo Nordisk are trying to develop a once-a-week basal insulin to replace the current once-a-day options – that would be a major advance is reducing the hassle factor in care. Research also continues on a glucose-sensitive insulin, in which the insulin would only take effect when your blood sugar rises. That would be a breakthrough, but investigators have spent decades trying to make it work.

Since its discovery, the ultimate goal of insulin has been to make it disappear, as that would mean diabetes has been cured. It turns out that insulin therapy may indeed disappear someday, even if no cure is found. Since its discovery, the ultimate goal of insulin has been to make it disappear, as that would mean diabetes has been cured. It turns out that insulin therapy may indeed disappear someday, even if no cure is found.

Stem-cell therapy has long held promise in diabetes – specifically, making insulin-producing beta cells from stem cells, which the body would either tolerate on its own (perhaps by encapsulating the cells) or through immunosuppressant drugs. Progress has been halting but is now evident. Douglas Melton began his research in this area in 1991, and in 2014, he reported that his lab was able to turn human stem cells into functional pancreatic beta cells. The company that Melton created for the effort was acquired by Vertex Pharmaceuticals, and earlier this year, Vertex announced that it had received approval to begin a clinical trial on a “stem-cell derived, fully differentiated pancreatic islet cell therapy” to treat type 1 diabetes. Another company, ViaCyte, also announced this year that it will begin phase 2 of a clinical trial using encapsulated cells in hopes that they will mature into insulin-secreting beta cells.

It may take 10 to 15 years, but leaders in the field are cautiously optimistic that a cell-based therapy will someday provide a better option than insulin.

Diabetes would survive, but the therapy once touted as its cure would be dead.

Because I have a soft spot for happy endings – and because so much of own life has been intertwined with insulin – I have my own vision for insulin’s last hurrah.

A group of researchers in Europe are conducting a clinical trial to prevent type 1 diabetes. Called the Global Platform for the Prevention of Autoimmune Diabetes, the initiative began in 2015, and researchers are testing newborns who are at risk of developing type 1 to see if prevention is possible.

And what treatment are they using?

Oral insulin.

Like the discovery of insulin itself, this effort is a longshot, but if it works, insulin will have eradicated diabetes – a fitting coda for a medical miracle.

I want to acknowledge the following people who helped me with this article: Dr. Mark Atkinson, Dr. David Harlan, Dr. Irl Hirsch, Dr. David Nathan, Dr. Jay Skyler, and Dr. Bernard Zinman. Some material in this article came from my book, “Cheating Destiny: Living with Diabetes.”

About James

James S. Hirsch, a former reporter for The New York Times and The Wall Street Journal, is a best-selling author who has written 10 nonfiction books. They include biographies of Willie Mays and Rubin “Hurricane” Carter; an investigation into the Tulsa race riot of 1921; and an examination of our diabetes epidemic. Hirsch has an undergraduate degree from the University of Missouri School of Journalism and a graduate degree from the LBJ School of Public Policy at the University of Texas. He lives in the Boston area with his wife, Sheryl, and they have two children, Amanda and Garrett. Jim has worked as a senior editor and columnist for diaTribe since 2006.

Source: diabetesdaily.com

Asian Isn’t a Monolith: Why More Specific Data Matters in Diabetes Research

This content originally appeared on Beyond Type 1. Republished with permission.

By Kayla Hui, MPH

In the United States, diabetes affects 20 percent of the Asian American population, but that broad statistic doesn’t paint the whole picture. Despite being the fastest-growing racial group in the United States, health outcomes are often categorized by broad racial and ethnic categories, which limits our understanding of how diabetes truly impacts individual ethnic groups within the Asian diaspora. Disaggregated data—showing how diabetes impacts people from more specific origins—could help us better understand how to support and treat individual groups within the Asian American Pacific Islander communities.

“Asian Americans have 50 different ethnicities. Putting 50 ethnicities into one Asian American and Pacific Islander (AAPI) group—that is a fallacy,” H. Chris Hahm, PhD, MSSW, professor at the Boston University School of Social Work and lead researcher for the Epi Asian American Women’s Action In Resilience Empowerment (AWARE) study tells Beyond Type 1. According to the Pew Research Center, the majority of the 20 million Asians that live in the U.S. have roots that trace back to at least 19 countries in East Asia, Southeast Asia, or the Indian subcontinent.

Hahm says that because each ethnic group differs significantly across a variety of factors such as educational attainment, culture, and income level, having disaggregated data is imperative when trying to study diabetes among ethnic groups across the Asian diaspora.

For example, a research study, published in Diabetes Care, looked to understand the prevalence of type 2 diabetes among the U.S. South Asian communities when compared with four racial and ethnic groups: African Americans, white, Latinos, and Chinese Americans. In the study, South Asians include individuals originating from India, Pakistan, Nepal, Sri Lanka, and Bangladesh. While the study did not disaggregate based on ethnicity, after factoring in educational attainment, family income, and tobacco use, it was able to find that South Asians had a statistically significant higher age-adjusted prevalence of diabetes when compared to the aforementioned four groups.

The study also found that South Asians were significantly more likely to be insulin resistant and less likely to have responsive beta cell function, meaning the body could not compensate for the insulin resistance on its own. Data such as this helps us further understand that diabetes may develop differently among different groups and a one-size-fits-all approach to treatment is likely inadequate.

Poverty, a social determinant of health and diabetes, also differs by ethnic group. Hahm adds that grouping Asians together despite their varying levels of difference can be harmful when trying to understand the health disparities of different ethnic communities. “When you’re in poverty, you’re more likely to develop [type 2] diabetes or heart disease,” Hahm says. “That’s why it is really important to have disaggregated data.” As an example, 39.4 percent of Burmese Americans and 20 percent of Native Hawaiians and Pacific Islanders live in poverty; both fall within groups that experience higher rates of type 2 diabetes than other Asian subgroups. These correlations could point toward clues that could help better treat individual communities with a whole-person approach.

“Creating that visibility is the power of disaggregated data when it is meant to advance health equity. It is the basis for systemic change and empowerment of groups that have often not been heard,” Angela Glover Blackwell, JD, founder in residence at PolicyLink says in a report.

Unfortunately, having research studies solely focused on one ethnic group becomes challenging given the small amount of research funding allocated to studying the health of Asian Americans. Funding by the National Institutes of Health (NIH) only allocated 0.17 percent of the total NIH budget toward Asian Americans and Pacific Islanders (AAPI) from 1992 to 2018.

“AAPI researchers have a difficult time getting funded,” Hahm states. She adds that funding is so integral to a researcher’s career that without it, researchers wouldn’t get to continue studying their passions. “If you don’t get tenure, that means you are much more likely to go to other teaching universities,” Hahm explains. “This means your research is almost over.”

A report by PolicyLink titled Counting a Diverse Nation: Disaggregating Data on Race and Ethnicity to Advance a Culture of Health found that racial and ethnic health disparities and inequities can only be eliminated if quality data is available. By having disaggregated data by ethnicity, it can help track problems and underlying social determinants which can be used to create culturally-tailored approaches to medicine and public health.

Hahm hopes that more disaggregated research focused on ethnic Asian American groups can bring Asian American issues to the forefront, changing them from invisible to visible, and catalyzing a change in health outcomes for all Asian ethnic groups.

Source: diabetesdaily.com

Getting Started with Insulin if You Have Type 2 Diabetes

This content originally appeared on diaTribe. Republished with permission.

By Frida Velcani

New to insulin? Learn about insulin dosing and timing and how often to test your blood sugar levels if you have type 2 diabetes.

If you have type 2 diabetes, it is likely that your treatment regimen will change over time as your needs change, and at some point, your healthcare professional may suggest that you start taking insulin. While this might feel scary, there are millions of others living with type 2 diabetes and taking insulin, so it’s definitely manageable.

Click to jump down:

Why do some people with type 2 diabetes need to take insulin?

Type 2 diabetes can progress with time, which means that it gets more difficult for a person’s body to regulate glucose levels. The body’s many cells become less responsive to insulin (called increased insulin resistance), and the specific cells in the pancreas that produce insulin make less of it (called beta cell insufficiency). This is not necessarily related to a person’s diabetes management, and it is likely not possible to prevent.

For many people, adjusting lifestyle factors such as a reduced calorie diet and increased physical activity are key to keeping blood glucose levels stable and in a target range. Healthcare professionals may also recommend that people with type 2 diabetes take additional medications like metforminDPP-4 inhibitorsSGLT-2 inhibitors, or GLP-1 agonists to their treatment plan to improve glucose management, reduce A1C, lose weight, or support heart and kidney health.

When do people with type 2 diabetes start insulin?

After 10 to 20 years, many people with type 2 diabetes will begin insulin therapy, although every person’s journey with type 2 diabetes is different. This happens when lifestyle changes and medications aren’t keeping your glucose levels in your target range. It is important that you start treatment as early as possible to avoid persistent hyperglycemia (high blood sugar), which can lead to long-term health complications affecting your heart, kidneys, eyes, and other organs.

What are the different types of insulin?

The key to transitioning to insulin is knowing your options. Some people taking insulin need to use both a basal (long-acting) and a prandial (rapid-acting or “mealtime”) insulin each day, while others may only need to use basal insulin. Learn about your options here.

  • Basal (long-acting) insulins are designed to be injected once or twice daily to provide a constant background level of insulin throughout the day. Basal insulins help keep blood sugars at a consistent level when you are not eating and through the night but cannot cover carbohydrates (carbs) eaten for meals or snacks or glucose spikes after meals.
    • Some people use other medications, like GLP-1 agonists, to help cover mealtimes. GLP-1/basal combination treatments for people with type 2 diabetes combine basal insulin with GLP-1 agonist medication in one daily injection. This combination can effectively lower glucose levels while reducing weight gain and risk of hypoglycemia (low blood sugar). Learn more here.
  • Prandial (rapid-acting or “mealtime”) insulins are taken before mealtime and act quickly to cover carbohydrates eaten and bring down high sugar levels following meals. Ultra-rapid-acting prandial insulins can act even more rapidly in the body to bring down glucose levels. Rapid and ultra-rapid insulins are also taken to correct high glucose levels when they occur or are still persistent a few hours after a meal.
  • Basal and prandial insulins are both analog insulins, meaning they are slightly different in structure from the insulin naturally produced in the body. Analog insulins have certain characteristics that can be helpful for people with diabetes. Human insulins, on the other hand, were developed first and are identical to those produced by the human body. Human insulins are classified as regular (short-acting insulin) or NPH (intermediate-acting). These are generally cheaper than analog insulins and can be bought without a prescription at some pharmacies.

Although many people use both basal and prandial insulin – which is called multiple daily injections of insulin (MDI) and consists of one or two injections of basal insulin each day as well as prandial insulin at meals – people with type 2 diabetes who are beginning insulin therapy may only need basal insulin to manage their glucose levels. Basal insulin requires fewer injections and generally causes less hypoglycemia. For these reasons, many healthcare professionals recommend basal insulin when you first start insulin therapy.

How do I take and adjust my insulin doses?

It is important to learn the different methods of taking insulin and what kinds of insulin can be delivered through each method. There are several ways to take insulin – syringe, pen, pump, or inhalation – though injection with a syringe is currently the most common for people with type 2 diabetes. There are many apps that can help you calculate your insulin doses.

  • Insulin pens are considered easier and more convenient to use than a vial and syringe. There are different brands and models of insulin pens available. Smart pens are becoming increasingly common and can help people manage insulin dosing and tracking. They connect to your smartphone and help you remember when you took your last dose, how much insulin you took, and when to take your next one.
  • Insulin pumps are attached to your body and can be programmed to administer rapid-acting insulin throughout the day, to cover both basal and prandial insulin needs. When you need to take insulin for meals or to correct high glucose, calculators inside the pump can help determine the correct dosage after you’ve programmed them with your personal insulin pump settings.
  • Inhaled insulin is ultra-rapid acting insulin and can replace insulin used for mealtime and corrections of high glucose. It is taken through an inhaler and works similarly to injected prandial insulin. People with diabetes who do not want to inject prandial insulin might use this, but it’s not for people who only use basal insulin. The only approved inhaled insulin on the market is the ultra-rapid-acting mealtime insulin Afrezza.

Your insulin regimen should be tailored to fit your needs and lifestyle. Adjusting your basal insulin dosage and timing will require conversations and frequent follow-up with your healthcare team. When initiating insulin therapy, you may be advised to start with a low dose and increase the dose in small amounts once or twice a week, based on your fasting glucose levels. People with diabetes should aim to spend as much time as possible with glucose levels between 70-180 mg/dl. Insulin may be used alone or in combination with oral glucose-lowering medications, such as metformin, SGLT-2 inhibitors, or GLP-1 agonists.

One of the most important things to consider is the characteristics of different insulin types. To learn more, read “Introducing the Many Types of Insulin – Is There a Better Option for You?” and discuss with your healthcare team.

In order to dose insulin to cover meals or snacks, you have to take a few factors into consideration. Your healthcare team should help you determine what to consider when calculating an insulin dose. Prandial insulin doses will usually be adjusted based on:

  • Current blood sugar levels. You’ll aim for a “target” blood sugar, and you should know your “sensitivity” per unit of insulin to correct high blood sugar levels.
    • Insulin sensitivity factor (ISF) or correction factor:  how much one unit of insulin is expected to lower blood sugar. For example, if 1 unit of insulin will drop your blood sugar by 25 mg/dl, then your insulin sensitivity factor is 1:25. Your ISF may change throughout the day – for example, many people are more insulin resistant in the morning, which requires a stronger correction factor.
  • Carbohydrate intake. Insulin to carb ratios represent how many grams of carbohydrates are covered by one unit of insulin. You should calculate your carbohydrate consumptions for each meal.
    • Insulin to carbohydrate ratio:  the number of grams of carbs “covered” by one unit of insulin. For example, a 1:10 insulin to carbohydrate ratio means one unit of insulin will cover every 10 grams of carbohydrates that you eat. For a meal with 30 grams of carbohydrates, a bolus calculator will recommend three units of insulin.
  • Physical activity. Adjust insulin doses before, and possibly after, exercise – learn more about managing glucose levels during exercise here.

Learning to adjust your own insulin doses may be overwhelming at first, especially given the many factors that affect your glucose levels. Identifying patterns in your glucose levels throughout the day may help you optimize the timing and dosing of your insulin. Your healthcare professional, a certified diabetes care and education specialist, or insulin pump trainer (if you use a pump), can help guide you through this process. Do not adjust your insulin doses without first talking to your healthcare team.

How often should I test my blood sugar?

The frequency of testing will depend on your health status and activities during the day. Initially, you may be advised to check your blood glucose three to four times a day. As a starting point, check in with your healthcare team about how often to check your blood sugar. Many people test before meals, exercise, bedtime, and one to two hours after meals to ensure that they bolused their insulin correctly. Over time, your fasting, pre-meal, and post-meal blood glucose levels will help you figure out how to adjust your insulin doses.

Continuous glucose monitors (CGM) are particularly useful for tracking changes in glucose levels throughout the day. Some CGM devices also connect with an insulin pump to automatically adjust insulin delivery. After you start a treatment plan, the goal for most people is to spend as much time as possible in their target range. Talk with your healthcare professional about starting CGM and developing glucose targets.

What else do I need to know about taking insulin?

It’s common to experience minimal discomfort from needle injections or skin changes at the insulin injection site. You may also experience side effects of insulin therapy, which can include some weight gain and hypoglycemia. In some people, insulin increases appetite and stops the loss of glucose (and calories) in the urine, which can lead to weight gain. Hypoglycemia can occur if you are not taking the right amount of insulin to cover your carb intake, over-correcting high glucose levels, exercising, or consuming alcohol. Treating hypoglycemia also adds more calories to your daily intake and can further contribute to weight gain. Contact your healthcare professional to adjust your insulin dose if you are experiencing hypoglycemia, or call 911 if you experience more serious side effects, such as severe low blood sugar levels, serious allergic reactions, swelling, or shortness of breath.

Staying in contact with your healthcare team is the best way to make the transition to insulin therapy. Though the first few days or weeks will be challenging, with the right support, you’ll find a diabetes care plan that works for you.

If you were recently diagnosed with type 2 diabetes, check out more resources here.

Source: diabetesdaily.com

The PROTECT Study

This content originally appeared on Beyond Type 1. Republished with permission.

By Makaila Heifner

Let’s face it, there are a lot of research studies out there, and we mean… a lot. But one you should definitely know about is The PROTECT Study. Especially if you or a loved one was recently diagnosed with type 1 diabetes (T1D).

The PROTECT Study aims to understand how the investigational medicine, teplizumab, works in children and young adults who have recently been diagnosed with T1D, as well as assessing if there are any side effects while taking the medication. This treatment is still being evaluated in clinical studies and has not been approved by the FDA for treating T1D. In previous studies of high-risk individuals, teplizumab was shown to delay the onset of T1D an average of nearly 3 years (35 months).

Who Is Eligible for the Study?

This study will include 300 children and adolescents in clinics across the United States, Canada, and Europe that meet the following criteria:

  1. Age 8-17 years old
  2. Diagnosed with T1D in the previous 6 weeks
  3. Positive for 1 of 5 T1D autoantibodies (test to be done as part of the study) 4. Ability to produce a minimum amount of your own insulin (test to be done as part of the study)
  4. Otherwise generally healthy, with no other significant medical conditions, recent or history of infections, or taking medicines that might interfere with teplizumab

If you meet all the criteria, the next step is to visit a study clinic, where the study team will:

  • Discuss the study in more detail and explain what participation would mean for you or your child.
  • Talk through the potential benefits and risks of being involved in the study.
  • Ask questions and carry out medical tests to determine whether you or your child are right for the study and the study is right for you or your child.

If you and/or your child are interested in potentially participating in the PROTECT study, click here to find a study clinic near you.

Before the study begins, you/and your child must agree to and sign an Informed Consent Form which explains the study in detail, any potential risks or benefits of participation, as well as your rights and responsibilities as a participant of the study.

All study-related treatment and care will be provided to eligible patients without charge; however, patients will not receive any compensation for their participation in the study. Patients who decide to participate are able to withdraw from the study at any time for any reason.

Participants do not have to change their primary doctors as the study provides short-term study-related care only. Patients are encouraged to tell their regular doctors about taking part in a clinical research study. Some medicines are prohibited to take while part of the study so a patient’s doctor may want to contact the study physician to request additional information.

How Does It Work?

If you/or your child are selected to be part of this study, you/your child will be placed in one of two groups, either the teplizumab group or the placebo group (meaning you/your child will receive no treatment). Deciding who will be placed in each group is chosen at random by a computerized system, and neither you/your child nor the study doctor will know which treatment group you/your child was placed in. This is done so that results from the different groups can be handled the same way.

Over the duration of the study, you/your child will receive 2 courses of study medicine given by intravenous (IV) infusion. The IV infusion usually lasts about 30 minutes and will be given daily over 12 days on 2 separate occasions, 6 months apart.

The study will last just over a year and a half (the study reports the study will last up to 84 weeks) and require 36 study clinic visits, including the initial screening, treatment courses, and observation periods.

During visits to the study clinic, you/your child will be asked several questions and perform a series of study-related medical tests. These tests are done in order to understand how the treatment is affecting you/your child and how well the body is responding to the medication.

Identifiable information (for instance, name or address) will not be accessible to anyone who is not directly part of this study; additionally, The Sponsor (the company carrying out the study) will not have access to any personal information that is submitted through the study’s website.

Why?

The treatment works by interfering with the cells that destroy the insulin-producing beta cells in the pancreas. If the treatment successfully interferes with these cells (T cells) patients who are taking teplizumab may be able to continue producing their own insulin and reduce their need for insulin injections, have better control over their blood glucose, and experience fewer complications from T1D.

Visit theprotectstudy.com to learn more about PROTECT.

Source: diabetesdaily.com

Why #insulin4all Advocates Targeted Beyond Type 1

Beyond Type 1, the diabetes nonprofit, found itself in hot water recently after the organization sent a letter stating its apparent opposition to LD673, a proposed bill for an insulin safety net program in Maine. The Maine bill is modeled after Minnesota’s popular Alec Smith Insulin Affordability Act, and guarantees that people with diabetes can access inexpensive insulin in an emergency.

The letter stated that LD673 would “create not only administrative burdens to the Maine government and pharmacies in the state, but also unintended additional out-of-pocket expenses to people living with diabetes.” The organization seemed to argue that its own GetInsulin.org program, a partnership with the major insulin manufacturers, rendered further legislation “duplicative” and unnecessary. 

Some diabetes advocates were outraged at Beyond Type 1’s stance, and accused the nonprofit of favoring the big pharmaceutical companies over people with diabetes.

Late last week, the organization appeared to modify its stance with a new letter, this one explicitly supporting Maine’s new bill. Was it all just a misunderstanding, or did rowdy online activism cause Beyond Type 1 to change its tune?

LD673

Alec Smith, the Minnesota bill’s namesake, died of diabetic ketoacidosis (DKA) in 2017, at the age of 26. At the time, he had recently aged out of his parents’ health insurance plan, and the cost of his insulin had skyrocketed to about $1,300 a month, around half of his total earnings. 

Smith’s mother believes that he died because he could not afford to pay for the insulin that he needed to live. She has become a noted insulin activist, and helped turn his death into a major rallying cry for people protesting the nation’s outrageously high insulin prices.

Minnesota signed the Alec Smith Insulin Affordability Act in April 2020, to widespread acclaim in the diabetes community. 

The new bill in Maine, named An Act To Create the Insulin Safety Net Program, would similarly aim to provide cheap, emergency insulin to those with an urgent need. The emergency insulin would carry a maximum cost of $35 for one month’s supply. The bill also mandates standards for the insulin manufacturers’s otherwise voluntary patient assistance programs (PAPs).

The Letter

In the letter that would cause an uproar, Beyond Type 1 never explicitly stated opposition to the new legislation. Whatever its intentions, however, it’s fair to say that the organization strongly implied its opposition.

The letter argues that state-level legislation such as LD673 is no longer necessary, because nationwide circumstances have changed dramatically since the Alec Smith act was passed in Minnesota:

At the time of its passage, GetInsulin.org did not exist, nor did the urgent need programs offered by the manufacturer. Additional insulin copay, cash pay, and patient assistance programs became available after the Minnesota bill became law that insulin manufacturers’ patient assistance programs (PAPs) are enough to fill the gap in assistance, and that the state statute is not needed. 

While insulin is still disgracefully expensive in most of the US, it is true that there are now more avenues for patients in need than there were only a few years ago. Part of that is due to the success of advocacy efforts, such as the one that coalesced around Alec Smith’s death, that turned insulin affordability into a political hot topic. The Covid-19 pandemic has also shined a spotlight on healthcare inequities, pushing the insulin manufacturers to expand their affordability programs in the last year.

The Beyond Type 1 letter also concentrates heavily on extolling the GetInsulin.org website. GetInsulin.org is essentially a user-friendly portal for the PAPs, aggregating the information from all three major insulin manufacturers in a single space. The website was created in partnership with the big pharmaceutical companies and is at least partly funded by them, facts that raise the suspicions of many people with diabetes, who are often inclined to see Big Pharma as an adversary rather than a partner. 

Are PAPs Really Good Enough?

Patient assistance programs can be valuable and even life-saving resources for people struggling to afford insulin. In some cases, PAPs may even provide more generous support for patients in an emergency than that mandated by the Alec Smith Act and Maine’s proposed law. And because these patient support programs have a reputation for being difficult to access and navigate, there’s no reason to doubt that GetInsulin.org provides a valuable public service.

For insulin affordability advocates, that’s not nearly good enough. The Shot, a weekly digest of insulin affordability news, put the case plainly:

While it’s true that patient assistance programs have become more robust … the programs, like Beyond Type 1’s GetInsulin.org, are voluntarily offered by the companies — often at no cost to them as PAPs are generally tax deductible. The Maine bill, like the Minnesota one that precedes it, locks the companies into providing assistance that patients would otherwise have no guarantee will exist tomorrow.

The PAPs are only reliable as long as the manufacturers don’t dilute them in the future (or disband them entirely). Given that many Americans now feel that insulin is practically a byword for medical exploitation, one can hardly be surprised when people with diabetes regard these programs with suspicion.

The big three – Eli Lilly, Novo Nordisk, and Sanofi – are reliable opponents of government efforts to cap insulin prices. And it would seem that PAPs owe their recent expansion more to the immense public relations pressure that manufacturers have lately had to endure than to any one corporation’s sense of generosity or public service.

Experts do agree that insulin manufacturers do not alone bear the blame for high insulin prices. Manufacturers, pharmacy benefit managers, insurance companies, and pharmacies all benefit from high insulin prices, and our byzantine healthcare market incentivizes all of them to push for price increases. Patients can’t easily vote with their wallets, and are therefore left with little recourse to effect meaningful change.

Insulin affordability continues to be a disaster in the diabetes community. Insulin rationing due to high cost is widespread in the United States, a situation that has probably only gotten worse since the dawn of the pandemic and the economic devastation that has followed. 

The upshot of Beyond Type 1’s argument to the Maine legislative committee was that the PAPs, as accessed through GetInsulin.org, are pretty much good enough. If this wasn’t what the organization intended to communicate with its letter, it made a bad mistake – and on an electric issue.

Online Reaction

Insulin access advocates discovered the letter online, and were outraged. Several accused the organization of corruption and betrayal:

Twitter personality Miss Diabetes illustrated a particularly devastating comic, featuring a caricature of Beyond Type 1 co-founder Nick Jonas:

source: @miss__diabetes

A little context: when Beyond Type 1 was founded in 2015, the organization avowed a principled refusal to accept money from the pharmaceutical industry. Things have changed. Now, according to their website, “Beyond Type 1 partners with pharmaceutical companies, including insulin manufacturers, when the organization finds that doing so furthers mission and impact.” 

This isn’t unusual. Most other prominent diabetes nonprofits also accept Big Pharma money (#insulin4all campaigner T1International is one notable exception). Nevertheless, Beyond Type 1’s position on this issue seemed unusual. The American Diabetes Association, for example, took the opposite stance and penned a letter in support of the bill. 

BT1’s About-Face

Despite the controversy, Beyond Type 1 kept silent for weeks, further disappointing some in the diabetes online community.

In response to a request for comment, a Beyond Type 1 spokesman told Diabetes Daily that the original letter was written not to oppose the legislation but “with the intent of providing information to legislators about existing programs and tools for people with diabetes who are insulin-dependent.” 

Additionally, the spokesman said, “Our team has followed the community response closely, and we know some have interpreted our testimony as one of opposition.”

Soon thereafter, the organization sent a new public letter to Maine’s legislative committee, claiming that it did support LD673, and that it always had:

We’re writing today to clarify and state unambiguously that Beyond Type 1 does support the passage of this legislation. This legislation will help individuals in Maine who may be struggling under urgent or ongoing circumstances to access affordable insulin due to high list prices. Our hope is that people with diabetes who need financial assistance to pay for this life-essential drug may find it through existing programs or potentially those created through Maine’s efforts.

After news of the new letter broke, Hilary Koch, a Maine resident and a Policy Manager for T1International, declared victory on Twitter – but also qualified her celebration with a reminder of how much work needs to be done to achieve universal affordable insulin access.

One can only guess as to the effect that Beyond Type 1’s clarification might have the bill’s chances. Lawmakers may well have already been inclined to support the bill. Just last year, Maine passed more sweeping legislation capping insulin costs for those with state-regulated insurance.

 

Source: diabetesdaily.com

Tell the FDA What Delaying Type 1 Diabetes Would Have Meant to You

Imagine a treatment that could delay the progression of type 1 diabetes for years. How much would an extra year (or three or four) of good health have been worth for you or your loved one?

It could become a reality soon. This month, the United States FDA will evaluate what would be the first-ever approved treatment to delay Type 1 diabetes.

And you can help make it come true. In late May, the FDA’s advisory committee will review comments on the matter, including those from the general public. Just a single compelling letter from a person touched by diabetes could make a big difference.

We believe that it would be amazing to have an FDA-approved type 1 diabetes prevention treatment, and we hope that you’ll consider writing a letter of your own. We’ll provide instructions on how to do so at the bottom of this article. But first, a quick review of the proposed treatment and its potential:

Teplizumab

The novel drug is named Teplizumab. It’s been developed by ProventionBio, a biopharmaceutical company wholly dedicated to the prevention of autoimmune diseases.

When given to patients known to carry the antibodies that cause type 1 diabetes, Teplizumab delays the onset of symptoms by an average of nearly three years. And the effect may be even more potent than that. ProventionBio’s most important trial is still ongoing, and even after eight years some participants still appear to be benefiting from the treatment, which was given just once, in a single 2-week course.

Teplizumab was created decades ago, initially as an immunosuppressant, but researchers soon learned that it was especially effective at suppressing the specific T-cells known to attack the pancreatic Beta cells. Apparently, it can suppress that autoimmune attack for quite a long time.

How Teplizumab Might Change Diabetes Care

As of today, there is no validated way to slow type 1 diabetes,. Even if you have utilized antibody testing and know that a family member has an extremely high likelihood of developing type 1 diabetes, there’s little to do but keep watch for the symptoms of hyperglycemia.

But if Teplizumab gets approved, doctors would have a tool to help delay the onset of the disease for the first time.

And as Dr. Jeremy Pettus has explained, antibody screening would likely move into the mainstream. Even if Teplizumab were not indicated, antibody testing could also give many families valuable time to prepare for the progression of type 1 diabetes, months or years to learn about the condition and what to expect. That change could significantly reduce the frequency with which type 1 diabetes is diagnosed in the emergency room, only after the patient has experienced diabetic ketoacidosis (DKA).

How to Tell the FDA Your Story

It couldn’t be easier.

Here is the link to provide a comment for the FDA advisory committee that will rule on Tepluzimab’s application.

  • Write Your Comment
    • You can simply begin typing directly into the form, or you can attach a file.
  • Select a Comment Category
    • From the drop-down menu, select “Individual Consumer.”
  • Provide an Email Address. (Or Don’t).
    • A box allows you to provide an email address to receive confirmation that your comment has been received.
  • Provide Contact Information. (Or Don’t).
    • Decide whether you wish to provide your contact information, or you can file your comment anonymously. Your name will be made public, but none of your other information.

How to Write an Effective Comment

The FDA panel invites commentary from non-experts for a reason: they really want to hear the opinions of regular people. A good letter won’t just vanish into a slush pile.

This treatment is uncharted territory for the FDA, so the real-life experiences of people with diabetes and their caretakers might be especially relevant. While doctors and advocates will attest to the quantifiable medical benefit of delaying type 1, the experts on the advisory committee may not necessarily be able to imagine what those extra years could really mean for patients and their families.

Subjects that may be worth exploring in your comment:

  • The burdens and demands of living with type 1 diabetes, and the difficulty of a life totally reliant on insulin
  • The impact of what a two or three year delay in insulin dependence would mean to patients and families, including:
    • More time to live a normal life
    • More time for a patient and family to learn about the disease, prepare for it, safely manage it
    • Better long-term health, fewer complications
    • Lighter impact on families
  • How increased screening for type 1 diabetes antibodies will improve the standard of care and patient outcomes
  • How important those extra years of insulin-free life might be

Comments do not have to be long to be persuasive, but they should demonstrate a good understanding of the issues.

The government website also has a list of criteria to follow: click “Commenter’s Checklist” above the commenting form to pull up a pop-up window. It’s worth reading through.

For reference, you can look at comments that have already been posted here.

Deadline

Comments posted by the end of May 13 will be provided to committee members before the actual hearing, and will likely have the greatest opportunity to make an impact.

If you’ve missed the May 13 deadline, comments posted by the end of May 26 will still be taken into consideration.

 

Source: diabetesdaily.com

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