Carmella Evans-Molina, Yasminye D. Pettway, Diane C. Saunders, Seth A. Sharp, Thomas S. R. Bate, Han Sun, Heather Durai, Shaojun Mei, Anastasia Coldren, Corey S. Davis, Conrad Reihsmann, Alexander L. Hopkirk, Jay Taylor, Amber Bradley, Radhika Aramandla, Greg Poffenberger, Adel Eskaros, Regina Jenkins, Danni Shi, Ke Xu, Hakmook Kang, Varsha Rajesh, Swaraj Thaman, Fan Feng, Jean‐Philippe Cartailler, Alvin C. Powers, Kristin Abraham, Anna L. Gloyn, Joyce C. Niland, Marcela Briššová
Phenotyping and genotyping initiatives within the Integrated Islet Distribution Program (IIDP), the largest source of human islets for research in the U.S., provide standardized assessment of islet preparations distributed to researchers and enable the integration of multiple data types. Data from islets of the first 299 organ donors without diabetes analyzed using this pipeline highlights substantial heterogeneity in islet cell composition associated with hormone secretory traits, sex, reported race and ethnicity, genetically predicted ancestry, and genetic risk for type 2 diabetes (T2D). While α and β cell composition influenced insulin and glucagon secretory traits, the abundance of δ cells showed the strongest association with insulin secretion and was also associated with the genetic risk score (GRS) for T2D. These findings have important implications for understanding mechanisms underlying diabetes heterogeneity and islet dysfunction and may provide insight into strategies for personalized medicine and β cell replacement therapy. Our investigation highlights substantial heterogeneity in islet cell composition associated with hormone secretory traits, sex, reported race and ethnicity, genetically predicted ancestry, and genetic risk for type 2 diabetes (T2D).