A recently published Scientific Statement sheds light on new and improved treatment options for type 1 diabetes. Endocrine News speaks with first author Aaron W. Michels, MD, about the Statement’s implications and why this is an exciting time in type 1 diabetes research.
In July, the Endocrine Society published a Scientific Statement that highlights potential research directions related to the pathogenesis of type 1 diabetes (T1D) that should help with the development of new and improved treatment options.
The Scientific Statement summarizes research and suggested directions for new research in these areas related to T1D: genetics, heterogeneity, pathology of the pancreas, assessment of β cell function and mass, immunologic biomarkers in peripheral blood, changes in the exocrine pancreas, and screening to identify individuals at-risk for T1D.
“The Endocrine Society chose type 1 diabetes for a Scientific Statement because research related to T1D is rapidly expanding, and the field is poised for new advances. The hope is that the Scientific Statement will provide scientists, physicians, and funding agencies with a guide for areas of research that seem particularly promising,” says Alvin C. Powers, MD\, of Vanderbilt University Medical Center in Nashville, Tenn., a member of the writing group.
The statement is based on the authors’ updated version of the widely cited and often modified Eisenbarth model, which outlines the different stages of progression to type 1 diabetes. The Scientific Statement proposes that Stage 0 be added to this model which already included Stages 1, 2, and 3, to highlight that there are likely events occurring earlier in the disease that currently are not understood or being studied.
How Far We’ve Come – and Still Have to Go
Four years ago marked the 100th anniversary of the discovery of insulin; Leonard Thompson’s life was saved, and it changed the world. Until then, type 1 diabetes was basically a death sentence, and even when insulin became available, the average person with diabetes had to spend about half their income on insulin.
“The centennial celebration of the discovery of insulin in 2021 provided a reminder that this breakthrough has saved millions of lives, especially those with [T1D],” the authors of the Scientific Statement write.
Aaron W. Michels, MD, a professor of medicine at the Barbara Davis Center for Diabetes at the University of Colorado Anschutz, tells Endocrine News that centennial of insulin underscored how far we’ve come—yet also how far we still have to go, as T1D remains associated with significant morbidity and mortality. With rapid advances in immunotherapy, pancreas research, and disease staging, the field needed a unifying document to summarize current knowledge gaps and chart priorities for the next era of prevention and cure.
“We’re more than a century past the discovery of insulin and yet type 1 diabetes still carries a heavy burden,” Michels says. “With so many breakthroughs happening at once — from immunotherapies to studying the human pancreas — we felt the field needed a roadmap to identify what we know, what we don’t, and where we must go next.”
Theory to Reality
The authors of the Scientific Statement write that research in T1D is expanding and currently fall into 3 broad categories: (1) delivery of exogenous insulin (eg, insulin analogs, automated insulin delivery devices), (2) disease-modifying therapies to treat the underlying β-cell-directed autoimmunity (eg, teplizumab, B- or T-cell-directed interventions, anti-cytokine therapies, antigen-specific immunotherapies), and (3) therapies that seek to increase endogenous insulin production and secretion (eg, transplantation of insulin-producing cells or islets, protection or expansion of remaining endogenous β-cells, transdifferentiation of other cell types into insulin-producing cells).
According to Michels, the approval of teplizumab marked a paradigm shift in treating T1D as an immune-mediated disease rather than solely a metabolic one. Second, novel insights into human disease pathogenesis from studying the pancreas (pancreata) from organ donors with type 1 diabetes are rapidly expanding what’s biologically possible.
“The approval of teplizumab was a watershed moment because it proved we can delay the onset of type 1 diabetes by targeting the immune system,” Michels says. “At the same time, technologies like automated insulin delivery and stem cell-derived beta-cell replacement are moving from theory to reality – it’s an incredibly hopeful time.”
The authors write that programs like Network for Pancreatic Organ Donors with Diabetes (nPOD)and Human Islet Research Network and the Human Pancreas Analysis Program (HPAP) have revolutionized access to high-quality human pancreatic tissue from donors across the T1D disease spectrum. These resources now allow researchers to study early lesions, immune infiltration patterns, and cellular stress responses within islets in unprecedented detail.
Another point the authors make is that it is becoming increasingly clear that T1D is not a single disease, but a spectrum influenced by age of onset, genetic background, immune signatures, and rate of beta-cell loss. Defining subtypes could allow researchers to match therapies to disease mechanisms and clinicians to predict who will respond — or not respond — to specific interventions.
“We used to view type 1 diabetes as one disease, but we now realize there are multiple ‘flavors’ of it,” Michels says. “A child who develops T1D at age five may have very different biology than someone diagnosed at 35, and recognizing those differences could help us match the right therapy to the right person.”
Emerging Evidence
These new research avenues have led to new evidence that lead to breakthroughs and better outcomes for people with T1D. For instance, the authors of the ask a question in one of the Knowledge Gaps section on beta-cell function assessment about whether these beta-cells in someone with T1D could be “sleeping” and maybe recoverable. “Emerging evidence suggests that some beta-cells may be functionally silent rather than fully destroyed,” Michels says. “If we learn how to reactivate or rescue these dormant cells, it could open a path to restoring endogenous insulin production even in people with established T1D.”
A future effort the authors suggest is the continued development of clinically safe beta-cell tracers for in vivo imaging in humans. Michels explains that imaging pancreatic beta cells is a significant challenge as there are very few beta cells dispersed throughout the pancreas. “Having a safe and specific tracer would improve our ability to directly measure beta cell mass in real time,” he says.
Insulin Rationing Is Unacceptable
In November 2021, Endocrine News published an article titled “The Cost of Living (with Diabetes),” referencing a paper that appeared in the Mayo Clinic Proceedings detailing the account of a patient with type 1 diabetes in his mid-20s who worked as a restaurant manager in Minnesota. He couldn’t afford the deductible and monthly premiums of his insurance, and he couldn’t afford to pay for his insulin with cash, so he tried to ration his insulin. He was found dead in his apartment from diabetic ketoacidosis.
“Insulin rationing in a century-old disease is unacceptable,” Michels says. “Policy reform, expanded biosimilar competition, and decoupling insulin access from insurance status are all critical steps—alongside emergency access programs—to ensure that no one lacks a medication that’s been around for 100 years.”
In March 2023, Eli Lilly lowered the price on its most popular insulins, with Novo Nordisk and Sanofi following suit shortly thereafter, but only after the $35 monthly price cap for people on Medicare that was mandated by the Inflation Reduction Act. And while this was a dose of good news, experts warned that the Act was just the first step on a long journey.
The authors of the Scientific Statement pose the question of whether early screening for diabetes (which could be expensive, especially if implemented on a national scale) should be cost-effective or cost-agnostic, especially if early detection could offset financial burden on patients later in life.
“While cost is an unavoidable consideration for policymakers, I would argue that early screening may ultimately save money by preventing life-threatening diabetic ketoacidosis (DKA) and delaying disease onset,” Michels says. “In that sense, the real question may not be ‘Can we afford to screen?’ but ‘Can we afford not to screen for type 1 diabetes?’”
Transformational Era
Michels says that T1D research is entering a transformational era—where prevention and beta-cell restoration are no longer theoretical. But realizing that the future will require collaboration, investment, and a shift from managing disease to modifying its course.
“The biggest message we want to send is this: type 1 diabetes is no longer just something to be managed – it’s something we can delay and potentially reverse,” he continues. “But getting there will take collaboration across science, policy, and patient advocacy.”
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