ISLET INFLAMMATION AND PANCREATITIS IN CATS WITH DIABETES MELLITUS: HISTOPATHOLOGICAL ANALYSIS

In cats with diabetes mellitus (DM) few studies have characterized histopathological features of the endocrine and exocrine pancreas. Among them, some have shown that islet amyloid is a consistent finding and others that pancreatitis may be associated with DM. In a recent study we observed that hyperglycemia increases neutrophils in the exocrine pancreas. Aims of the present study were to assess whether diabetic cats have histopathological evidence islet inflammation or pancreatitis and to give detailed characterization of islet lesions, in comparison to a control population. Formalin-fixed, paraffin-embedded pancreatic samples were retrieved from diabetic and control cats that died at the Clinic for Small Animal Internal Medicine, University of Zurich (Switzerland). Control cats were selected from the archive to be matched for age, sex, breed and body weight. Consecutive slides were stained with hematoxilin-eosin, and double stained with insulin and myeloperoxidase (i.e., neutrophils), insulin and CD3 (i.e., T-lymphocytes), insulin and CD20 (i.e., B-lymphocytes), insulin and PCNA (i.e., proliferation marker), and glucagon and Ki-67 (i.e., proliferation marker). Cell counts and morphometric analyses were performed manually and with software, respectively. Data were analyzed with parametric tests. Thirty-seven diabetic cats and 20 controls were included. The mean insulin-positive cross sectional area was approximately 40% lower in diabetic than control cats (P<0.01) whereas that of glucagon was similar. In the islets, counts of neutrophils, T- and B-lymphocytes were not different between groups; of note, the presence of T- and/or B-lymphocyte was observed in 8 of 37 (21.6%) diabetic cats whereas in 1 of 8 (5.0%) controls. In the exocrine pancreas, a trend towards increased presence of necrosis and fibrosis was observed in diabetic cats (P=0.07); counts of neutrophils, T- and B-lymphocytes did not differ. Proliferation of insulin-positive and glucagon-positive cells was not different between groups. Proliferation of acinar cells in the exocrine tissue was 3-fold increased in diabetic cats (P<0.01), in particular nearby islets (6-fold, P<0.001). The results may suggest that in feline DM a subset of cats presents infiltration of the islet with lymphocytes. It is possible that the lymphocytes contribute to β-cell loss and dysfunction. In addition, pancreatitis may be present in some cats, although observing necrosis and fibrosis but not inflammatory infiltrates remains unclear. The increased proliferation rate of acinar cells deserves further investigation. In humans this finding has been associated with chronic pancreatitis.