Immune system targets single beta cells before Type 1 diabetes symptoms show

Researchers from the University of Florida’s Diabetes Institute have found an important clue for why the body’s immune system destroys insulin-producing cells in the pancreas, which leads to Type 1 diabetes. They found that single beta cells and small clusters of these cells die first, and larger islet cells are initially more resistant to the immune system, according to a study published in the November 2025 issue of Diabetes. (It was published online in July 2025.)

“The finding is interesting because researchers traditionally focus on the islets of Langerhans, and these other insulin cells are not usually their focus,” Denise M. Drotar, Ph.D., the study’s lead author and a postdoctoral researcher at UF Health, said in a news release.

Type 1 diabetes is a disease where the immune system destroys insulin-producing beta cells in pancreatic islets. About 2 million Americans have Type 1 diabetes. The islets of Langerhans are named for German pathologist Paul Langerhans, who in 1869 saw that the cell clusters under a microscope resembled islands in a sea of pancreatic cells.

The smaller cells are rarely a focus of research, but understanding the disease’s progression could one day lead to earlier diagnosis and strategies that can prevent or delay progression, researchers said.

In this analysis, researchers used advanced imaging and computer analysis to examine slides of pancreatic tissue from the UF Health-based Network for Pancreatic Organ donors with Diabetes, or nPOD. It’s the largest biorepository of pancreatic tissue used for Type 1 diabetes research.

Only donors who were less than 20 years of age were included in the analysis because those who are older are not widely screened for autoantibodies. Researchers analyzed samples from 60 people without diabetes, 29 who were positive for autoantibodies and 56 who were diagnosed with Type 1 diabetes. Those with diabetes were further segmented by age: 0 to 1 year, 1 to 7 years and over the age of 7. Those who were positive for autoantibodies were segmented by those that had a single autoantibody and those that had multiple antibodies.

The study revealed that smaller insulin-producing clusters vanished early in the disease process, while larger islets remained mostly intact in samples from people with early-stage disease.

“We did not expect that,” corresponding author Clive H. Wasserfall, Ph.D., a researcher at the UF Diabetes Institute, said. “And we can only speculate as to why that would be.

Frequencies of insulin and glucose in all sizes of cells of those with Type 1 diabetes decreased compared with those samples of those who did not have diabetes. Researchers also found that samples from younger patients who are in the earlier stages of Type 1 diabetes had lower beta cell content compared with donors who developed the disease later in life. This, researchers said, supports “the notion that immune-mediated loss of beta cells is more aggressive in younger individuals.”

“We observed age-related differences in endocrine composition and islet frequency in pancreata from donors without diabetes. Age-corrected data revealed decreased islet frequency and greater inter-islet distance in the T1D pancreas,” they wrote.

Researchers suggest additional studies that would reveal the functional relevance of these endocrine cell clusters and single cells and the factors that drive their destruction, particularly in younger individuals at high risk of diabetes.