2021 marks the 100th year since Sir Frederick Banting, Charles Best, and Professor John Macleod from the University of Toronto reported the successful treatment of canine diabetes with a pancreas extract, now known as insulin. This discovery represented not only a remarkable scientific achievement, but more importantly, provided a life-saving intervention for individuals diagnosed with type 1 diabetes. Over the past century and through a series of highly collaborative international research efforts, astounding progress has been made toward understanding how type 1 diabetes develops, altogether supporting the identification of disease predictive biomarkers, calculation of type 1 diabetes risk scores, and conduct of clinical trials testing dozens of candidate therapies attempting to prevent or reverse the disease. Indeed, University of Florida Diabetes Institute (UFDI) investigators have served in key roles for the vast majority of these efforts, and in honor of the field’s collective progress, they have recently contributed in writing a number of invited articles for various publication outlets.
We would first highlight “Strategies for durable b cell replacement in type 1 diabetes,” published in by Todd Brusko, PhD (Scientific Director for the UFDI, Professor of Pathology and Pediatrics), Holger Russ, PhD (University of Colorado Denver), and Cherie Stabler, PhD (Professor, J. Crayton Pruitt Family Department of Biomedical Engineering at UF).
The UFDI boasts a highly interdisciplinary team of investigators with expertise in autoimmunity, pancreas biology, and clinical endocrinology, with unique prowess in research bridging these arenas with biomedical engineering. Indeed, Dr. Stabler’s lab within the J. Crayton Pruitt Family Department of Biomedical Engineering seeks to develop biomaterials-based solutions to improve long-term outcomes of islet cell transplant for individuals living with type 1 diabetes.
“This review highlights the dramatic and exciting advancements made in cell-based therapies for Type 1 diabetes. It also discusses how cross-collaborations with diverse and innovative clinicians, biologists, immunologists, and engineers are necessary to develop a comprehensive and functional implant,” said Stabler. “One hundred years after the discovery of insulin, I am truly excited about what the next ten years hold for treatment options in Type 1 diabetes.”
Beyond this, Dr. Stabler, Dr. Brusko, and Clayton Mathews, PhD were recently granted a competitive continuation of an NIH grant supporting the development of a novel islet:immune chip (iiChip) platform allowing for dynamic studies of how live human islet cells interact with immune cells in real-time. The goal of the project is to expedite clinical interventions to prevent and reverse type 1 diabetes by facilitating more rapid models of the disease.
Additionally, in collaboration with Mark Atkinson, PhD (UFDI Director, Eminent Scholar, and Professor of Pathology and Pediatrics) and Dr. Mathews, Edward Phelps, PhD (Assistant Professor of Biomedical Engineering) has conducted seminal work imaging cellular signaling events in live pancreas slices providing key information on defects present in islets from persons with type 1 diabetes. Underscoring the importance of these research partnerships linking biomedical engineers to the UFDI, Dr. Atkinson and Benjamin Keselowsky, PhD (Professor and Associate Chair for Graduate Studies, Department of Biomedical Engineering) co-direct an NIH T32 supported Interdisciplinary Graduate Program in Type 1 Diabetes and Biomedical Engineering, representing the only curriculum of its kind in the United States. This program, which supports four graduate students each year, prepares early career researchers with the unique skillsets needed to address new and emerging questions in the field of type 1 diabetes using biomedical engineering approaches.
Dr. Brusko’s lab also published a recent review titled, “De-coding genetic variants in type 1 diabetes” for an Immunology & Cell Biology Special Feature. This manuscript overviews the known genetic risk variants for type 1 diabetes located within the protein-coding regions of 10 genes, and their functional contributions toward both autoimmunity and b-cell fragility in the disease development.
“The scientific community has made incredible strides from the original discovery of insulin that have drastically improved the lives of those living with the disease,” said Brusko. “However, we must not lose sight of the fact that there is an incredible amount of work left to do. The research community still needs a better means to predict and prevent the disease from occurring in those with increased risk. We also need to restore endogenous insulin production in those who already live with type 1 diabetes. Finally, industry and governments must do a better job of making insulin more affordable to patients and their families. All in all, modern medicine should celebrate one of the most profound and life-saving discoveries, but we must not lose sight of the continued challenge posed by moving an acute fatal condition into a chronic disease. Insulin does not, and will not, represent a cure.”
Also in celebration of insulin’s centennial, Dr. Atkinson provided an invited contribution to a curated collection of stories from leading type 1 diabetes researchers and clinicians titled, “Voices: Insulin and beyond,” published in Cell Metabolism.
“While I join with many in commemorating the centennial of the discovery of therapeutic insulin, one of my goals in acknowledging it is to emphasize that for many, both domestically and internationally, the ability to see access to this life-saving drug remains a challenge. This, for multiple reasons including pricing strategies, public health care emphasis, insurance policies, and more. Hopefully, this will soon see change to a more accessible setting and one in line with the thoughts of those that made the important discovery,” said Dr. Atkinson.
In addition, UFDI investigators, Michael Haller, MD (Chief of Pediatric Endocrinology) and Ashby Walker, PhD (UFDI Director for Health Equity Initiatives, Department of Health Services Research, Management & Policy) are pioneering Project ECHO Diabetes, which is a $7M collaboration with Stanford University that extends specialized diabetes care and education to patients in underserved communities across the state of Florida. Specifically, Project ECHO provides access to continuous glucose monitoring and in-home HbA1c testing, a peer-coaching system for improved diabetes education, real-time telemedicine consults, as well as team-based video conferencing to enhance local primary care providers’ diabetes knowledge.
The UFDI also has a long-established history of leadership in type 1 diabetes clinical trial networks including T1D TrialNet and TEDDY (The Environmental Determinants of Diabetes in the Young). Dr. Haller and Martha Campbell-Thompson, DVM, PhD (Professor and Molecular Pathology Core Director) are currently directing a trial to measure changes in pancreas volume over time using MRI in individuals at-risk for developing type 1 diabetes (NCT02234947). Additionally, enrollment will soon begin for another TrialNet trial (NCT04291703), led by Dr. Haller, evaluating low-dose anti-thymocyte globulin (ATG) for the ability to delay type 1 diabetes in subjects with high-risk for the disease. This trial will build on a multitude of bench-to-bedside efforts led by UFDI investigators, which have consistently demonstrated that low-dose ATG can preserve endogenous insulin production in persons recently diagnosed with type 1 diabetes. With the potential to delay the disease progression, Haller and colleagues hope low-dose ATG will provide meaningful improvement in long-term outcomes for individuals with and at-risk for type 1 diabetes.
While the efforts noted here represent only a snapshot of the diverse areas of active investigation, it is clear that UFDI researchers have established themselves as leaders and innovators advancing the collective understanding of mechanisms at play in type 1 diabetes development and devising new methods to prevent and reverse the disease.
Over the past century, the meaning of a type 1 diabetes diagnosis has changed dramatically, and innovations in insulin delivery and glucose monitoring devices continue to improve quality of life for those touched by this disease. Going forward, the UFDI remains committed to its mission of working together for a diabetes-free world.