Two experts discussed the underlying mechanisms of progression in type 1 diabetes in a debate on Monday, June 24, at the 84^th Scientific Sessions. Jamie L. Felton, MD, Assistant Professor of Pediatrics at Indiana University School of Medicine, argued that immune cells precipitate disease advancement, while Edward Phelps, PhD, Associate Professor of Biomaterials, Regenerative Medicine, Immunoengineering, and Diabetes at the University of Florida, argued that beta cells are a more influential factor.

“You are going to hear people tell you that beta cells are uniquely sensitive to inflammatory stress. I’m going to show you an exhibit with evidence that will show you they are not uniquely sensitive to this stress,” Dr. Felton said to kick off Do Immune or Beta Cells Drive Transition from Stage 1 to Stage 3 Type 1 Diabetes?

Dr. Felton shared data demonstrating that beta cells have specific, sustainable, and adaptive stress responses designed to cope with stress. She provided further evidence that the response of type 1 diabetes beta cells to stress is not unique and that immune cells are required for beta cell endoplasmic reticulum stress before type 1 diabetes.

She also shared research demonstrating that hybrid insulin peptides occur spontaneously whether or not someone has diabetes, that congenital beta cell defects do not lead to islet autoimmunity, and that islet autoantibody prevalence is not increased in checkpoint-inhibitor diabetes. Further, she explained that type 1 diabetes is prevalent among monogenic autoimmunity mutations.

“The bottom line is that type 1 diabetes is an immune problem that leads to an endocrine defect,” she concluded.

Dr. Phelps shared evidence demonstrating that dysfunctional beta cells cause insulitis in mice without natural autoimmunity. 

“Beta cells can summon immune cells to the islet through the release of chemokines, generation of neoantigens, class 1 regulation of human leukocyte antigen (HLA), and release of extracellular vesicles containing autoantigens,” Dr. Phelps said and explained that beta cells hyper present mutated antigens.

“This is catnip to T-cells,” he said.

He also presented data showing that beta cells from donors with type 1 diabetes have uncoordinated calcium responses that are not responsive to glucose and that beta cells are dysfunctional regardless of T-cell infiltration.

Dr. Phelps maintained that the best way to prevent type 1 diabetes is to change the beta cells.

“Beta cells themselves are susceptible to whatever’s going on between the T-cells that are attracted to their location and their eventual demise,” he said.

The debate can be viewed on-demand by registered meeting participants on the virtual meeting platform. If you haven’t registered for the 84^th Scientific Sessions, register today to access the valuable meeting content through Aug. 26.