The diagnosis of insulitis in human type 1 diabetes

Consensus definition of insulitis

Patients with insulitis are defined by the presence of a predominantly lymphocytic infiltration specifically targeting the islets of Langerhans. The infiltrating cells may be found in the islet periphery (peri-insulitis), often showing a characteristic tight focal aggregation at one pole of the islet that is in direct contact with the peripheral islet cells. The infiltrate may also be diffuse and present throughout the islet parenchyma (intra-insulitis). The lesion mainly affects islets containing insulin-positive cells and is always accompanied by the presence of (pseudo)atrophic islets devoid of beta cells. The fraction of infiltrated islets is generally low (<10% of islet profiles). The lesion should be established in a minimum of three islets, with a threshold level of ≥15 CD45⁺ cells/islet before the diagnosis can be made. The pathology report should include the total number of islets analysed, the fraction of islets affected by insulitis, the fraction of (pseudo)atrophic islets, and a description of the spatial relationship of the infiltrate to the insulin-positive islet cells