Researchers continue to make progress in understanding the pathogenesis of type 1 diabetes and the complex mechanisms that drive the transition from the early stages of autoantibody positivity to clinical hyperglycemia.

At the session Do Immune or Beta Cells Drive Transition from Stage 1 to Stage 3 Type 1 Diabetes?, a pair of accomplished researchers will debate the relative roles of beta-cells and immune cells in the process of beta-cell loss and loss of insulin secretion. The session will take place on Monday, June 24, from 3:15 p.m. – 4:15 p.m. ET in Room W304 A-D of the Orlando Convention Center.

Jamie L. Felton, MD, Assistant Professor of Pediatrics in the Division of Pediatric Endocrinology and Diabetology at the Indiana University School of Medicine and Herman B Wells Center for Pediatric Research, will argue that type 1 diabetes progression is precipitated by immune cells.

“Over the last couple of decades, there has been increased recognition of beta-cell contribution to type 1 diabetes progression, and I agree that beta-cell stress can aggravate immune insult,” Dr. Felton said. “However, beta-cell destruction in type 1 diabetes requires abnormal immune responses, so I would argue that type 1 diabetes is an immune problem that leads to an endocrine defect, not vice versa. This is one of the reasons that agents used to support the beta-cell in type 2 diabetes cannot be used to prevent or delay onset.”

While she admits that, to date, immune interventions have had limited success preventing onset, Dr. Felton posits that this is due to insufficient understanding of the immune response and appropriate targets. She points out that the immunotherapy drug teplizumab is currently the only U.S. Food and Drug Administration (FDA)-approved treatment indicated to delay the onset of stage 3 type 1 diabetes.

“The bottom line is, it’s impossible to address the beta-cell alone to avoid type 1 diabetes progression,” Dr. Felton said. “Therefore, efforts to target the immune system should be a priority in type 1 diabetes research and clinical trial design.”

Edward A. Phelps, PhD, Assistant Professor in the Department of Biomedical Engineering at the University of Florida and UF Diabetes Institute, will take the position that type 1 diabetes progression is precipitated by beta-cells.

“When looking at the extent to which beta-cells participate in the progression of type 1 diabetes, I think there are several interesting pieces of evidence to consider that support the idea that beta-cells are a key driver of that process and not just a passive victim,” Dr. Phelps said. “Beta-cells, for example, are essentially able to actively call immune cells to their location, whether it’s when they are infected with a virus or they have an inflammatory signature happening.”

Additionally, he said, there is evidence that, before beta-cells are destroyed, they start to become abnormal and lose their ability to respond correctly to glucose.

“There is also evidence for beta-cell senescence, which may be analogous, so I don’t think this is simply driven by immune cells that seek and destroy a target, but there is an interaction happening that requires active participation by beta-cells,” Dr. Phelps said. “So, I don’t think we can just focus solely on things like T-cell receptors and autoantigens. We also need to understand and consider all of the small perturbations that might have big effects.”

For registered participants unable to attend the 84^th Scientific Sessions in person, this debate will be available on-demand on the ADA virtual meeting platform following the meeting.