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Since healthy pancreatic islets consist of ~65% beta cells, this would lead to reduced islet size, while the number of islets per pancreas volume (islet density) would not be affected. In this study, we compared the islet density, size, and size distribution in biopsies from subjects with recent\u2010onset or long\u2010standing T1D, with that in matched non\u2010diabetic subjects. The results presented show preserved islet size and islet size distribution, but a marked reduction in islet density in subjects with recent onset T1D compared with non\u2010diabetic subjects. No further reduction in islet density occurred with increased disease duration. Insulin\u2010negative islets in T1D subjects were dominated by glucagon\u2010positive cells that often had lost the alpha\u2010cell transcription factor ARX while instead expressing PDX1, normally only expressed in beta cells within the islets. Based on our findings, we propose that failure to establish a sufficient islet number to reach the beta\u2010cell mass needed to cope with episodes of increased insulin demand contributes to T1D susceptibility. Exhaustion induced by relative lack of beta cells could then potentially drive beta\u2010cell dedifferentiation to alpha\u2010cells, explaining the preserved islet size observed in T1D compared to controls.<\/jats:p>","DOI":"10.1002\/cjp2.140","type":"journal-article","created":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T14:25:56Z","timestamp":1567866356000},"page":"248-255","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Characterisation of the endocrine pancreas in type 1 diabetes: islet size is maintained but islet number is markedly reduced"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1419-450X","authenticated-orcid":false,"given":"Peter","family":"Seiron","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala 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