The diabetic syndrome of the ‘BB’ Wistar rat: Possible relevance to Type 1 (insulin-dependent) diabetes in man

The diabetes which occurs spontaneously in the ‘BB’ Wistar rat has many affinities with human Type 1 (insulin-dependent) diabetes. It occurs in a non-obese, standard, laboratory rat derived from a non-inbred Wistar line. Both sexes are affected, with onset corresponding approximately to the time of sexual maturation. Both genetic and immune factors are involved in the aetiology, but their precise nature remains to be defined. Evolution of the overt clinical syndrome occurs over a period of hours to a few days. An intense insulitis is found, accompanied by selective destruction of B cells. Although insulitis may precede diabetes by many weeks, within 7–21 days after glycosuria the B cells are completely destroyed and have disappeared and the islets are few, small and with little residual inflammation. If untreated, marked wasting of body tissues, including fat and muscle protein, dehydration, and ketosis supervene. Careful study of littermates reveals glucose intolerance in 10%–25%, accompanied always by insulitis and these rats may subsequently develop insulin-dependent diabetes. Marked lymphopenia, mainly of thymus-derived (T) lymphocytes, both precedes and is sustained during glucose intolerance and overt diabetes. This lymphopenia appears to be associated reliably with insulitis, and may be a simple marker of susceptibility thereto. Abnormalities of nerves, testicles, and a tendency towards increased frequency of lymphomas have been found. Further research in this animal could lead to insights into aetiology, pathophysiology and complications potentially applicable to man.