Type 1 Diabetes Cure: What Can We Expect from Immunology Specialists?

To best meet our readers’ expectations, we asked our subscribers to choose the topic they were most interested in regarding immunology. This article addresses one of the most popular questions. You can also find our two other articles from this special IDS coverage, available in open access: "Beyond Autoantibodies: How to Optimize Type 1 Diabetes Screening?" and "Therapies to Alter the Course of Type 1 Diabetes and Achieve a Cure: Exploring Diverse Pathways".

After five days of congress sessions, including 21 plenary lectures, numerous scientific discussions, and over 20 hours of cumulative presentations, the word “cure” was mentioned barely a dozen times—and not always in the context of T1D. This raises a valid question about the role of diabetes immunology in a potential cure, especially for those already living with the condition. Yet, this limited mention could be more understandable than it seems.

T1D is an illness of autoimmunity. Research efforts, debates, and strategic roadmaps are all driven by the need to better understand its complex mechanisms. This focus has led to the development of an international consensus on how the disease progresses, as was highlighted in most sessions at the Bruges Congress. While the precise triggers of the disease remain elusive, its progression stages are now well-documented.

From an initial genetic risk, the process moves to immune activation and response, often accompanied by the development of a single diabetes-related autoantibody. Stage 1 follows, marked by the presence of two or more autoantibodies alongside normal blood glucose levels. Then comes Stage 2, characterized by abnormally high blood glucose without symptoms, as beta cells progressively lose their insulin-producing capacity. Finally, Stage 3 brings clinical diagnosis and symptoms, signalling the start of lifelong insulin dependence.

Thus, individuals living T1D are already unwell long before beginning insulin therapy—a key aspect of current research paradigms. Consequently, the IDS community focuses on strategies to alter the disease’s natural progression by decoding and modulating the autoimmune response. The ultimate goal is to prevent the disease from manifesting as early as possible.

However, no such prevention currently exists. The only approved disease-modifying therapy, Teplizumab, merely delays the onset of Stage 3 by a few months or years. Therefore, the cure for T1D is not seen as an immediate goal but rather as a hoped-for consequence of future immunotherapies.

Modulating autoimmunity should ideally lead to long-term preservation of pancreatic beta cells. This would maintain sufficient insulin production to regulate blood sugar without external insulin administration.

Speaking to Glucose toujours, Belgian professor and researcher Chantal Mathieu, a member of the IDS local organizing committee, emphasized the importance of slowing disease progression. She described the current era as exciting, thanks to “disease-modifying therapies now in clinical trials, alongside Teplizumab”, which she hopes will “soon gain approval in Europe for individuals with Stage 2 diabetes, as it already has from the U.S. Food and Drug Administration”.

For immunologists, the critical challenge lies in identifying therapies that could redefine chronic diabetes treatment: eliminating insulin injections through the preservation of intact beta cells, provided intervention happens early enough.

While the pathway from early diagnosis to insulin-free treatment is promising, it excludes individuals who have already lost their beta cells. In such cases, where preserving pancreatic beta cell mass is no longer viable, the focus shifts to a “practical cure.” This approach aims to replace beta cells while circumventing autoimmunity—an area where diabetes immunology has a significant role to play.

Chantal Mathieu acknowledged this disparity, stating: “When it comes to finding a cure for people who’ve been living with the condition for years, we must recognize that it’s a different disease.” Reflecting on progress in technology like sensors, pumps, and hybrid closed-loop systems, she admitted, “This isn’t a cure; it’s a different way of managing the disease compared to a few years ago.”

The Belgian professor asserts with conviction: "We are still working on a cure, and it will probably come from cell transplantation. [...] But this is not enough. We need sufficient sources of beta cells, as well as immunotherapy, because what we know is that there will first be an allogeneic reaction, hence rejection. Moreover, in the case of T1D, very specifically, the autoimmune disease will reappear, and this is a very difficult problem to solve."

Indeed, while we know the power of memory lymphocytes, which, once trained to recognize a pathogen—for example, through a vaccine—can fight it more quickly and effectively, this represents an additional hurdle for people living with T1D. As the professor explains, "The memory of an immune system is much harder to manage than its primary response." Chantal Mathieu predicts strong similarities between the phenomena occurring in graft recipients and those recently diagnosed. Consequently, disease-modifying therapies for newly diagnosed individuals will provide valuable insights for maintaining islet cell grafts.

This leads to the central question: “Is islet transplantation ready for its big moment?”—the title of the only session specifically dedicated to functional cures. While the connection between cell replacement therapy and immunotherapy seems obvious during a scientific congress on T1D, the limited time allotted to this topic is surprising. Only 1 hour and 15 minutes of the entire IDS congress are devoted to presenting, sharing, and confronting the perspectives of islet transplant specialists and immunology experts. Yet, the session's first speaker, Jason Gaglia from Harvard Medical School, affirms: "There are issues that IDS can help resolve in this field."

Invited to discuss the progress and challenges of islet transplantation, Dr. Gaglia reviewed various related topics: available cell sources, regulatory aspects, implantation sites, immune protection strategies, and clinical outcome measures. His remarks were driven by a straightforward observation: "If we want a therapy that can treat all people with T1D, ensuring an affordable production cost and an unlimited cell source is essential."

One key focus was on cadaveric islets, which, while reliable, are limited in quantity and present significant regulatory challenges. Classified as cellular therapy in the U.S., they are considered organ donations in Europe, Canada, and Australia. Regulatory guidelines are evolving, which may benefit clinical trials in the future, enabling standardization of inclusion criteria.

The discussion also touched on genetically modified islets, as seen in trials by the U.S.-based biotech Sana Biotechnology, and stem-cell-derived islets from companies like Vertex Pharmaceuticals and Seraxis. Additionally, the necessity of managing animal breeding for xenotransplantation was addressed.

On the topic of transplantation sites, after mentioning the commonly used portal vein of the liver, Dr. Gaglia highlighted a recent case reported by Glucose toujours of a successful autologous transplant in China. Conducted in the anterior sheath of the rectus abdominis muscle, he suggested, "This could revolutionize transplantation sites, as a minimally invasive procedure achieved insulin independence as early as day 75."

Turning to immunology and the critical need to protect transplanted cells, Dr. Gaglia noted, "Traditional immunosuppression approaches carry risks of infections and renal toxicity. We must go beyond these to effectively protect islets." New immunosuppression strategies are under testing, such as the successful use of agents like anti-CD40 ligand at the University of Chicago’s Transplantation Institute.

Finally, regarding the evaluation of cell replacement therapies, Dr. Gaglia proposed focusing on insulin independence and normal glycemic control as the primary criteria. "These should become our priority, replacing historical measures like low beta scores based on insulin dose, glycated hemoglobin, or C-peptide secretion."

While prospects for cellular replacement therapy are promising, several audience questions highlighted the economic challenges of transplantation, particularly regarding stem cells. On this issue, Dr. Gaglia was unequivocal: "We cannot bankrupt healthcare systems. Economic feasibility will be crucial to making these treatments accessible to a broader audience." With current therapy costs nearing one million dollars per patient, the only path to broad deployment lies in cost reduction through standardized products derived from cell banks.

This article is part of a three-part series on the Immunology of Diabetes Society Congress. To ensure free access to this content, the series is funded by IDS. Glucose toujours retains full editorial independence.

Translation reviewed by Anna Jones