Viruses and the pathogenesis of diabetes mellitus

Animal models, most notably EMC-induced murine diabetes mellitus, have demonstrated convincingly a juvenile-type of diabetic state in the genetically susceptible host. There is evidence that one site of genetic control in mice relates to differences in viral receptors on the surface of the beta cells that may confer susceptibility or resistance to EMC-virus-induced diabetes. The availability of β cell tissue culture techniques, assuming that such cultivation does not render β cells nonspecifically susceptible to any virus, has potential in screening for possible diabetogenic viruses in man. Animal models of virus-induced diabetes in primates could offer the possibility to study carefully the evolution of diabetic complications. Certain animal models and human studies are consistent with an autoimmune component playing a part in the genesis of JIDM. A viral infection and an autoimmune process are not incompatible with each other: A virus can trigger an autoimmune event and an autoimmune phenomenon can heighten susceptibility to a a diabetogenic virus. The pathologic entity of insulitis in JIDM is compatible with a viral and/or autoimmune process being operative etiologically. Genetic studies of twins concordant and discordant for JIDM suggest an environmental component, such as a viral infection, in the etiology of this type of diabetes. HLA associations have been established with JIDM, but the nature of the gene product(s) of specific HLA haplotypes is not known. Pancreatic islet cell antibodies (ICAb) are associated with JIDM. Whether ICAb are formed in response to a viral or autoimmune process, or, whether they actually play a role in the etiology of JIDM is unclear. Epidemiologic investigations reveal a relationship of JIDM with seasonal patterns and, in certain studies, an association with increased titers of neutralizing antibodies to Coxsackie-B viruses. While a seasonal variation in JIDM can be explained by a concomitant seasonal variation in viral infections, other interpretations (such as dietary and exercise alterations) are also possible. Although these findings, taken together, suggest a role for certain viruses and other environmental factors (drugs, toxins, foods) in the pathogenesis of JIDM, further studies will be necessary to establish unequivocally such relationships and to define the specific mechanisms that are operative.