Figure 2. Pancreatic changes and immune abnormalities in T1D.

The reduction of pancreas size or volume from normal to stage 2 to stage 3 T1D is shown at the top of the figure. The insets below shows a stylized section of the pancreas with islets and acinar cells in stage 2 and stage 3 T1D. Circulating autoantibodies directed at islet-enriched molecules are present in stage 2 and stage 3 but are not cytotoxic. In stage 3, immune cells are present within islets and exocrine pancreas, and there is a loss of both β cells and acinar cells. Other changes (not shown) in the stage 3 T1D islets include (a) insulin-negative, pseudoatrophic islets with rare islets appearing normal or having β cells; (b) alterations in proinsulin and insulin processing and expression of islet-enriched transcription factors such as PDX-1 and NKX6.1; (c) islet cell hyperexpression of HLA class I and class II molecules; (d) insulitis (immune cell infiltration in some islets) is variable, involving primarily CD8⁺ T cells, but also B lymphocytes, CD4⁺ T lymphocytes, and macrophages; CD20⁺ B lymphocytes are more common in recent-onset T1D in younger individuals; and (e) β cell mass is variable in stage 1, 2, and 3 (see Figure 1). Changes in the exocrine pancreas include (a) reduced pancreatic volume/mass at T1D onset and in autoantibody-positive individuals; progressive decline in pancreas volume in first 5 years of T1D; (b) acinar cell loss, some exocrine fibrosis in stage 3 pancreas; and (c) leukocyte infiltration of exocrine compartment. See text for additional details.