Morphometric and functional studies of islets in diabetes-prone BB/W rats that are discordant for overt diabetes

Autoimmune destruction of beta cells in BB rats is preceded by insulitis but it is not known if insulitis invariably leads to diabetes. We have quantitated mononuclear cells per unit of islet tissue in non-diabetic diabetes-prone BB rats that had escaped diabetes. Diabetes develops before the age of 140 days in the vast majority of these rats. It is assumed that rats that have reached the ages of 200 and 300 days without developing hyperglycaemia would never have become diabetic. Perfusion of the pancreata of such animals revealed a reduction in both baseline and glucose-stimulated insulin secretion. Histologically, there was a decrease in volume density of endocrine cells compared to age-matched diabetes-resistant control rats. In the 200-day old non-diabetic diabetes-prone BB rats 55.3 ± 4.0% of islets contained immunocytes and the number of immunocytes per 1,000 μ² of islet tissue averaged 53.8 ± 12.8 compared to 12.2 ± 0.8% in age-matched diabetes-resistant BB controls (p <0.05). Qualitatively similar but quantitatively less important changes were observed in 300-day old rats. We conclude that diabetes-prone BB rats that escape overt diabetes may nevertheless exhibit a marked increase in immunocytes associated with subtle loss of endocrine volume and function. Thus, in diabetes-prone BB rats discordance rates for 'insulitis' defined here as a statistically significant increase in immunocytes, are less than those for overt diabetes. This may mean that an event subsequent to the development of insulitis determines the extent of β-cell destruction.