Abnormalities of the Exocrine Pancreas in Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is considered a pancreatic beta cell-specific disease that results in absolute insulin deficiency. Nevertheless, clinical studies from 1940 onwards showed that patients with T1D had an abnormal exocrine pancreas due to the presence of subclinical exocrine insufficiency and acinar atrophy. Exocrine abnormalities are an important, and mostly neglected, characteristic associated with T1D. It is however still unclear whether the exocrine dysfunction in T1D is a primary damage caused by the same pathogenic event that led to beta cell destruction or secondary to beta cell loss. In this review, we collect evidence supporting the hypothesis that T1D is a combined endocrine-exocrine disease in which the loss of functional beta cell mass is most clinically apparent.

Purity of islet preparations and 5-year metabolic outcome of allogenic islet transplantation

“…21 There was, however, no difference concerning diabetes duration or GAD levels between the two LOW purity and HIGH purity groups in the present study. Several mechanisms such as alterations of exocrine pancreas depending on the duration of T1D and exposure to autoantibody levels may contribute to increased CA19-9.…”

Multi-color electron microscopy by element-guided identification of cells, organelles and molecules

“…T1D is caused by loss of the insulin-producing beta cells due to an auto-immune reaction of which the trigger is not known. More recently, the exocrine pancreas has been proposed to play a role in the destruction of beta cells, either by enhanced infiltration of immune cells in an animal model31 or by the notion that T1D patients have a 30% reduction in pancreas weight32. Our observation may also hint to a malfunctioning of differentiation, or may reflect an exocrine/endocrine cell interaction, which opens the intriguing possibility that exocrine cells may interfere with beta cells.…”

“…Although we only observed this in Islets of two diabetic rats (total of 32 cells), not in two controls, a conclusive statement whether or not this phenomenon relates to a (pre)diabetic state should await results from a follow-up study. This will include examining human pancreas32, but is beyond the scope of this paper.…”

Revisiting multiple models of progression of β‐cell loss of function in type 1 diabetes: Significance for prevention and cure

“…For example, increased CD8 + , CD4 + , and CD11c + T cell infiltration has been observed in exocrine pancreas from T1D patients and it was considered that this could contribute to the pathogenesis of T1D . In addition, it has been proposed that T1D is a combined endocrine–exocrine disease in which the loss of functional β‐cell mass is most clinically apparent . The high risk of autoimmune thyroiditis and celiac disease in T1D patients suggest that T1D is associated with a systemic autoimmune condition.…”