New Evidence of Exocrine Pancreatopathy in Pre-symptomatic and Symptomatic Type 1 Diabetes

Type 1 diabetes (T1D) is one of the most frequent chronic autoimmune diseases in humans, characterized by the lack of insulin production resulting in high blood glucose levels and lifelong requirement of exogenous insulin administration for survival. It is now recognized that the autoimmune process begins years before the clinical onset, in a stage called pre-symptomatic T1D, in which the presence of β-cell-specific autoantibodies is detectable. Our aim is to review evidence for T1D as a "whole-pancreas disease," featured by both endocrine and exocrine pancreas alterations already at early disease stages.

In this review, we discuss a series of recent observations indicating that in genetically predisposed individuals, structural and functional abnormalities as well as immune cell infiltration of the exocrine pancreas are already present in the pre-symptomatic stages of the disease. Despite T1D being considered a β-cell-specific disease, numerous reports point to the presence of exocrine pancreas subclinical abnormalities occurring during disease development. These observations challenge the long-standing idea that T1D exocrine damage exists as a mere consequence of disease progression and provide further explanation of mechanisms underlying T1D pathogenesis.