Novel imaging technology sheds light on how type 1 diabetes progresses
Two studies have used a sophisticated novel imaging technology to visualize the pancreas and gain new insights into how type 1 diabetes progresses—knowledge that could inform strategies to prevent or halt the disease. Type 1 diabetes is an autoimmune disease in which the immune system destroys the insulin-producing β (beta) cells found in clusters called islets in the pancreas. In two recent studies, researchers used a novel technology, called imaging mass cytometry, to analyze pancreases from female and male organ donors with type 1 diabetes of varying disease duration, as well as female and male donors without the disease. The technology allowed the scientists to measure simultaneously over 30 cellular markers and visualize at a single-cell level not only β cells and other pancreatic cell types, but also immune cells involved in the autoimmune attack. This novel technology enabled an unprecedented look not only at the numbers and characteristics of various cell types in the pancreas, but also at how cells interacted with each other, and provides an exciting resource for future studies.
Both studies confirmed that there were significant differences in the number and types of cells found in islets from different individuals. The studies also confirmed that β cell numbers were reduced in pancreases from donors with type 1 diabetes compared to those without disease, although there were differences observed among the donors. For instance, a surprising finding from one of the studies was that two donors with new-onset disease had a similar proportion of β cells in their pancreas as those without disease. This finding suggests that even at type 1 diabetes onset when people are showing clinical symptoms and need to take insulin to lower their blood glucose (sugar) levels, their pancreas may still have high numbers of β cells. Further experiments also suggested that, as type 1 diabetes progresses, the β cells go through an altered state, in which they display fewer characteristic features of β cells, before they are destroyed by the immune system.
The technology also enabled scientists in both studies to begin exploring the immune cell environment that plays a role in type 1 diabetes—looking at many different immune cell types at the same time and cataloging the number and timing of immune cell interactions with pancreatic cells. For example, one finding was that certain types of immune cells (T cells) were abundant in people with new-onset type 1 diabetes and less abundant in people with long-standing disease, suggesting that the immune system attack is maximal around the time of disease onset and that immune cells leave islets after β cells are destroyed.
By using imaging mass cytometry, these research groups not only painted a new and more vivid picture of type 1 diabetes disease progression, but also demonstrated the promise of this technology to garner new knowledge about the type 1 diabetes disease process. Results from these and future studies could help to inform the development of new therapies to prevent or treat the disease.
Damond N, Engler S, Zanotelli VRT,…Bodenmiller B. A map of human type 1 diabetes progression by imaging mass cytometry. Cell Metab 29: 755-768.e5, 2019.
Wang YJ, Traum D, Schug J,…Kaestner KH. Multiplexed in situ imaging mass cytometry analysis of the human endocrine pancreas and immune system in type 1 diabetes. Cell Metab 29: 769-783.e4, 2019