Insulitis in Type 1 Diabetes: A Sticky Problem

Lymphocytic infiltration in the islets of Langerhans is generally recognized as the defining lesion in young patients with recent-onset type 1A diabetes. In a landmark article published in Diabetes in 1965, Gepts (1) described insulitis in 70% of cases with acute diabetes and found that the lesion only affected islets with residual β-cells in pancreatic organs that had otherwise lost most of their β-cell mass. He concluded that the disease was probably caused by a protracted β-cell–specific (auto)immune process, thereby initiating a domain of study that has led to many new insights into the disease process, the identification of preclinical markers, and the definition of new intervention strategies.

Unfortunately, our knowledge of the early disease processes leading to the specific destruction of β-cells is far from complete. Among other things, it is still unknown what event triggers the T-cell–mediated inflammatory process, why the infiltrate of predominantly CD8⁺T-cells and macrophages is limited to the islets of Langerhans and only β-cells are destroyed, against which antigen the inflammatory infiltrate is directed, and whether this antigen is of an endogenous or exogenous nature (2–5). This lack of knowledge is, to a considerable extent, caused by the scarcity of material regarding those recently diagnosed with type 1 diabetes, of which only several dozen cases have been described in the literature (6). It is especially due to the virtual absence of material regarding pre-diabetic individuals …