Protein-free diets do not protect high-incidence diabetes-prone BioBreeding rats from diabetes

Dietary factors have been reported to affect the development of spontaneous diabetes in various colonies of inbred and outbred diabetes-prone (DP) BioBreeding (BB) rats. Several studies have attributed a protective effect to a diet omitting crude protein mixtures in favor of purified casein, hydrolyzed casein, or free amino acids. We have used inbred BB rats, all of which become diabetic in specific pathogen-free (SPF) conditions when fed ordinary rat chow, to test the capacity of 2 different protein-free diets to modulate BB rat diabetes in 2 distinct pathogen-free environments. BB rats known to all develop diabetes by 100 days of age were fed from birth with 1 of 3 diets. By 120 days of age, 100% of the animals on a standard diabetogenic chow diet, 83% of animals on an amino acid-based protein-free diet, and 100% of animals on a hydrolyzed casein-based diet had developed diabetes (P >.05). A slight delay in the age of onset was observed among rats fed the amino acid-based diet, but this delay coincided with a reduction in weight gain among these animals compared with the rats on a standard diet. Histology showed insulitis in all rats at either diabetes onset or 120 days of age. We conclude that our unique strain of specific pathogen-free BB rats are not protected from diabetes when fed an amino acid-based diet and suggest that their insensitivity to dietary manipulation may be due to an as yet unknown factor present in the diabetes-resistant (DR), but not the DP BB rat genetic background.