Insulitis in human type 1 diabetes The quest for an elusive lesion

The histopathology of type 1 diabetes is defined by a decreased beta-cell mass in association with insulitis, a characteristic lymphocytic infiltration limited to the islets of Langerhans and prominent in early stage disease in children. A cytotoxic T-cell mediated destruction of insulin-producing beta-cells is thought to be initiated by an unknown (auto) antigen, leading to the destruction >75% of beta-cell mass at clinical diagnosis. Although considered to be pathognomonic for recent onset disease, insulitis has only been described in approximately 150 cases over the past century. This review describes the quest for this elusive lesion and gives its incidence in various patient subpopulations stratified for age of onset and duration of the disease. It discusses recent new insights into the regenerative capacity of the beta-cell mass in the pre-clinical stages of the disease and relates these findings to the inflammatory processes within the islet tissue.