Diabetes, Vol 46, Issue 7 1133-1140, Copyright © 1997 by American Diabetes Association
Dietary cow's milk protein does not alter the frequency of diabetes in the BB rat
S Malkani, D Nompleggi, JW Hansen, DL Greiner, JP Mordes and AA Rossini
Department of Medicine, University of Massachusetts Medical School, Worcester, USA.
One theory of the pathogenesis of IDDM proposes that exposure to cow's milk
proteins triggers the disease in genetically susceptible individuals. We
tested this hypothesis in the BB/Wor rat model of human IDDM.
Diabetes-prone (DP) BB/Wor rats spontaneously develop IDDM. Coisogenic
diabetes-resistant (DR) BB/Wor rats do not develop diabetes spontaneously,
but IDDM can readily be induced by treatment with
polyinosinic:polycytidylic acid and depletion of RT6+ T-cells. Pregnant
BB/Wor rats were fed one of four experimental diets or a standard Purina
commercial rat chow (5010) that was certified to be free of cow's milk
protein. Offspring were maintained on the maternal diet after weaning.
DP-BB/Wor rats, fed either of two experimental diets based on hydrolyzed
casein and free of intact milk protein (Nutramigen or D11236), developed
diabetes at only half the rate of animals fed Purina 5010 chow. Neither the
addition of bovine serum albumin (BSA) to Nutramigen nor the substitution
of total milk protein for the hydrolyzed casein in the D11236 diet
increased the frequency of spontaneous diabetes. In contrast, there was no
relationship between diet and susceptibility of DR-BB/Wor rats to IDDM
induction. However, the methods used to induce IDDM in DR-BB/Wor animals
were found to induce antibodies against BSA. We conclude the following: 1)
Dietary modification can reduce spontaneous IDDM expression in DP-BB/Wor
rats, but the agent of protection is not elimination of cow's milk protein.
2) The addition of BSA or intact milk protein does not abrogate the
effectiveness of a protective diet. 3) The genetic susceptibility of the
DR-BB/Wor rat to autoimmune diabetes is unaffected by any of the tested
diets, but a role of anti-BSA-like autoreactivity in IDDM expression cannot
be excluded.