Long-term complications of virus-induced diabetes mellitus in mice

In man, the early metabolic abnormalities associated with diabetes mellitus are followed by various long-term complications 1 . The cause of these complications is not clear, but they may be secondary to persistent abnormalities in blood glucose levels 2 . In mice, several viruses can infect and destroy pancreatic β cells and produce acute-onset insulin-dependent diabetes mellitus (IDDM) characterized by hypoinsulinaemia, hypergly-caemia, glycosuria, polydypsia and polyphagia 3 . The virus most studied is the M variant of encephalomyocarditis (EMC) virus 4,5 . Long-term complications, however, have been difficult to demonstrate because in most mice, the diabetes is transient and mild. Recently, by plaque purification, we have shown that the M variant of EMC virus actually has two stable variants: one diabetogenic (designated D) and the other nondiabetogenic (designated B). Further studies revealed that the B variant reduces the severity of the diabetes produced by the D variant 6 . We now report that when mice are inoculated with the D variant alone, many develop severe and prolonged hyperglycaemia followed by some of the long-term complications of diabetes, including reduced lifespan, glomerulosclerosis and ocular changes.